Advances in Therapeutics and Diagnostics
Bisphosphonates
Julie T. Lin, MD, and Joseph M. Lane, MD
Bone resorption and formation are normally linked and
therefore maintain bone strength. When the metabolic
linkage is altered, bone structural and material proper-
ties decline. Postmenopausal and glucocorticoid-
induced osteoporosis, Paget’s disease of bone, and
fibrous dysplasia are some of the conditions in which
there is high-turnover bone resorption, leading to bone
with impaired structure susceptible to fracture. Low
bone mineral density (BMD) occurs when the rate of
resorption exceeds that of formation. High-turnover
states ensue with disproportionately increased osteo-
clastic activity, resulting in increased resorption.
Bisphosphonates interfere with osteoclast activity and
thus decrease the rate of bone resorption. Similarly,
metastatic disease of bone, especially the lytic phase,
appears to be mediated by both osteoclastic resorption
and other mechanisms. The use of bisphosphonates has
dramatically changed the clinical course of some
patients with cancer by decreasing the morbidity of
skeletal involvement.
Structure and Mechanism of Action
Bisphosphonates are pyrophosphate analogues in
which the oxygen in P–O–P has been replaced by a car-
bon, resulting in a metabolically stable P–C–P structure
resistant to enzymatic destruction. Bisphosphonates
have two side chains: R1 affects binding affinity to
bone; R2 affects antiresorptive capacity and, possibly,
side-effect profile. Bisphosphonates vary in potency
based on these specific side chains (Fig. 1). Etidronate is
a non–nitrogen-containing bisphosphonate with a simple
alkyl side chain, whereas pamidronate and alendronate
contain basic aminoalkyl groups. Risedronate and
zolendronate contain heteroaromatic rings with nitrogen-
containing side chains. Tiludronate is a sulfur-containing
bisphosphonate.
First-generation bisphosphonates, such as etidronate
and clodronate, inhibit bone formation and bone resorp-
tion equally. With each successive generation, there has
been increased potency, with more selectivity for inhibi-
tion of resorption and less inhibition of bone formation.
Second-generation bisphosphonates include pamid-
ronate and alendronate; the third generation includes the
highly potent risedronate and zolendronate.
Vol 11, No 1, January/February 2003
Bisphosphonates have a particular affinity for areas
of increased bone turnover, such as in metastatic bony
lesions and Paget’s disease. They primarily work by
inhibiting osteoclast function using two main mecha-
nisms. First, bisphosphonates have a high affinity for
hydroxyapatite of bone, binding to it irreversibly and
therefore inhibiting osteoclast-resorbing surface.
Second, absorbed bisphosphonates inhibit osteoclast
function by interfering with their critical biologic path-
ways. Short-chain bisphosphonates such as clodronate
inhibit the Krebs cycle; long-chain bisphosphonates
such as alendronate inhibit the fatty chain pathway
and the ability to form biologic membranes. Bis-
phosphonates also exhibit apoptotic effects on osteo-
clasts.
Pharmacokinetics
Oral bisphosphonates have a very low bioavailability
and poor gastrointestinal absorption rates (from <0.7%
for alendronate and risedronate to 6% for etidronate
and tiludronate). Oral absorption can be diminished
even further in the presence of mineral water, other liq-
uids, or food in the stomach. Absorbed bisphosphonate
remains mainly in the skeleton for prolonged periods
(half-lives of 1.5 to 10 years), whereas nonincorporated
bisphosphonate is excreted in the urine within two
passes through the kidney.
Dr. Lin is Fellow, Rehabilitation Medicine and Metabolic Bone Disease,
Hospital for Special Surgery, New York, NY. Dr. Lane is Chief,
Metabolic Bone Disease Service, and Medical Director, Osteoporosis
Prevention Center, Hospital for Special Surgery, New York.
One or more of the authors or the departments with which they are affili-
ated has received something of value from a commercial or other party
related directly or indirectly to the subject of this article.
Reprint requests: Dr. Lane, 535 East 70th Street, New York, NY 10021.
Copyright 2003 by the American Academy of Orthopaedic Surgeons.
J Am Acad Orthop Surg 2003;11:1-4
1
Bisphosphonates
PO3H2 H PO3H2 H PO3H2
H CH2 OH N (CH2) OH
2
N (CH2)
PO3H2
H PO3H2
H
Etidronate Pamidronate Alendronate
Figure 1 Structural formulas of five bisphosphonates.
Indications for Use
Indications for bisphosphonates include such conditions
as postmenopausal and glucocorticoid-induced osteo-
porosis, Paget’s disease, osteolytic and osteoblastic bone
metastases, and other orthopaedic problems, such as
fibrous dysplasia, heterotopic ossification, and myositis
ossificans. Off-label uses are supported by results of
controlled clinical trials.
Many bisphosphonates have been shown to be effica-
cious in the management of postmenopausal and gluco-
corticoid-induced osteoporosis. Currently, however,
only oral alendronate and risedronate are approved for
both the prevention and treatment of osteoporosis. Oral
bisphosphonates reduce the risk of hip fracture by as
much as 50%. Because of the incidence of gastrointesti-
nal symptoms with oral bisphosphonates, treatment
with intravenous pamidronate and zolendronate may be
indicated for patients unable to tolerate even weekly
dosages of oral alendronate and risedronate.
Alendronate has been proved to be effective in post-
menopausal osteoporosis. In 2,027 women with preexist-
ing vertebral fractures, alendronate 5 mg daily for 24
months, then increased to 10 mg, resulted in fewer radio-
graphic vertebral fractures in the treatment group.1 Risk
of clinical fracture was 13.6% in the alendronate group
versus 18.2% in the placebo group. There was an average
increase in lumbar spine BMD of about 5% after 1 year,
then 1.5% per year for the next 2 years. At the end of 3
years, there was an increase in BMD of about 6% in the
femoral neck and about 7% in the trochanter. In the
Fracture Intervention Trial,2 3,658 osteoporotic women
with either vertebral fracture or osteoporosis at the
femoral neck were treated with alendronate for 3 to 4
years. There was decreased risk of fracture in the treated
women, with relative risks of 0.47 for hip fracture , 0.52 for
radiographic vertebral fracture, 0.55 for clinical vertebral
fracture, and 0.70 for all clinical fractures. Alendronate
has marked efficacy for men and for individuals on
steroids. A single weekly dose is as clinically effective as
daily dosage but with lower incidences of dyspepsia,
esophagitis, and gastroesophageal reflux disease (GERD).
Risedronate also is effective in increasing BMD and
reducing fracture risk. An oral daily dose of risedronate
2 Journal of the American Academy of Orthopaedic Surgeons
PO3H2 PO3H2
N
N
CH2 OH N CH2 OH
OH
3
PO3H2 PO3H2
PO3H2
Risedronate Zolendronate
(5 mg) resulted in BMD increases after 6 months of ther-
apy, and at 24 months, lumbar spine BMD increased
from baseline by 4%, with increases of 1.3% and 2.7% in
the femoral neck and femoral trochanter, respectively.3
In 2,458 postmenopausal women, those receiving oral
risedronate 5 mg daily increased BMD by 3% to 4% in
the femoral neck, femoral trochanter, and lumbar spine
at 3 years.4 Risk of new vertebral and nonvertebral frac-
tures also decreased. A single weekly oral dose of 35
mg is as effective as a daily dosage. Risedronate dimin-
ishes the hip fracture rate by 50%.
Parenteral pamidronate also has been successfully
used in the treatment of osteoporotic postmenopausal
women intolerant to oral bisphosphonates. In 36
patients, five courses of cyclical intravenous pamid-
ronate was effective in reducing bone turnover. 5
Thirteen patients who received 30 mg of pamidronate
intravenously over 3 months had an increased BMD of
6.2% in the lumbar spine and 4.7% in the hip.6 To date,
no fracture rate data have been reported for pamid-
ronate.
Parenteral zolendronate administered at annual inter-
vals produced effects on bone turnover and BMD com-
parable to those seen with oral bisphosphonates in the
treatment of postmenopausal osteoporosis. In one trial,
increases in the treatment group were 4.3% to 5.1% high-
er for the spine than in the placebo group (P < 0.001),
with suppressed biochemical markers of bone
formation.7 No fracture prevention data for zolen-
dronate are currently available.
Etidronate, alendronate, risedronate, and tiludronate
are all efficacious in the management of Paget’s disease.
A 400-mg daily dose of etidronate for 6 months, a 40-mg
daily course of oral alendronate for 6 months, a 30-mg
daily dose of risedronate for 2 months, or a 400-mg daily
dose of tiludronate for 3 months controls Paget’s
disease.8 In addition, several intravenous infusions of
pamidronate are effective.
Bisphosphonates can affect patients with bony
metastatic disease in a number of ways. They control
hypercalcemia, reduce bone pain, delay skeletally related
events (SREs), reduce the number of pathologic frac-
tures, and, in some cases, prolong survival. Initially, oral
clodronate and, subsequently, intravenous pamidronate

have been shown to reduce the number of vertebral frac-
tures in patients with myeloma.9 In a pooled group of
1,962 women with advanced breast cancer, administra-
tion of pamidronate 90 mg reduced the rate of SREs by a
mean of 30%.10 All studies showed a delay in the median
time to SREs. Zolendronate has been shown to be as
effective as pamidronate and should be combined with
either chemotherapy or hormonal therapy in women
with metastatic bone disease. Zolendronate 4 mg in a
15-minute infusion has been utilized in hormone refrac-
tory prostate cancer metastatic to bone. Results showed
a statistically significant advantage over placebo in
delaying the first SRE (P = 0.011), a reduced proportion of
patients having SREs (P = 0.021), and decreased overall
skeletal morbidity (P = 0.006).11 Zolendronate is the first
bisphosphonate shown to be effective in both lytic and
blastic metastatic disease.
Pamidronate decreases fractures in osteogenesis
imperfecta, controls Paget’s disease, and reverses the
bone changes of fibrous dysplasia. Alendronate has
been used off-label for fibrous dysplasia.12 Further-
more, oral and intravenous etidronate may be helpful in
treating fibrous dysplasia. Bisphosphonates work by
inhibiting the bone mineralization of ectopic bone
matrix that can occur in acute episodes.
Drug Interactions and Adverse Effects
Bisphosphonates generally should not be taken with
antacids that contain aluminum or magnesium, bottled
water containing minerals, or calcium supplements
because these agents decrease bisphosphonate absorp-
tion. In addition, food renders bisphosphonates ineffec-
tive; a 2-hour interval between meals and the adminis-
tration of a dose is recommended. Aminoglycosides
taken with bisphosphonates may cause severe hypocal-
cemia.
Adverse effects from oral bisphosphonates include
gastrointestinal complications such as gastritis or
esophagitis, abdominal pain, nausea, vomiting, diarrhea,
and constipation. To minimize gastrointestinal inflam-
mation and ulcer, patients should remain upright (sitting
or standing) for at least 30 minutes after taking the med-
ication. In patients with a questionable history of GERD,
incremental dosage increases are advisable. For exam-
ple, one dose (alendronate 70 mg) can be given the first
month, then every 2 weeks, then weekly while monitor-
ing for evidence of intolerance. Tolerance is generally
improved with once-weekly rather than daily dosing.
Electrolyte disturbances such as hypocalcemia and
hypophosphatemia may occur. Renal impairment may
result, and bisphosphonates should be used sparingly in
patients with renal insufficiency. Etidronate impairs
Vol 11, No 1, January/February 2003
Julie T. Lin, MD, and Joseph M. Lane, MD
mineralization of newly formed bone and may result in
osteomalacia and fracture if taken in large doses. Less
common reported side effects include hallucinations,
taste disorders, pseudomembranous colitis, iritis,
arthralgia, pericarditis, hepatotoxicity, and scleritis.
Overdosage of bisphosphonates may result in hypocal-
cemia.
Intravenous pamidronate and zolendronate may
cause bone pain, fever, and malaise. Bone pain may be
more likely to occur when intravenous infusions of these
bisphosphonates are taken without calcium. Influenza-
like symptoms may be particularly associated with intra-
venous bisphosphonates but may be managed with
diphenhydramine and acetaminophen before infusion.
Furthermore, adverse side effects may be minimized
with increased infusion time and volume.
Bisphosphonates are contraindicated in patients with
hypocalcemia or severe renal impairment (creatinine
clearance <30 mL/min) and in those who cannot remain
upright for at least 30 minutes. In addition, bisphospho-
nates should generally be avoided in those with sympto-
matic GERD, gastrointestinal bleeding, Crohn’s disease,
or malabsorption syndromes; in women of childbearing
age; and in patients who have been receiving bisphos-
phonate therapy for 7 years. Studies have shown that
alendronate used for 7 years in postmenopausal osteo-
porosis was well tolerated and effective. While no stud-
ies link bisphosphonates to birth defects in humans, ani-
mal studies have linked bisphosphonates with fetal
abnormalities. The effect of bisphosphonates in delaying
fracture healing has been raised.13 Peter et al14 showed
no delay in fracture repair and mechanical restoration
but did show retardation of callus remodeling.
Dosage and Cost
Bisphosphonates are available for both oral and intra-
venous administration. Dosages and costs are dependent
on the condition being treated and length of therapy
(Table 1).
Summary
Bisphosphonates are powerful antiresorptive agents
appropriate for use in patients with many metabolic
bone disease states. They are effective in enhancing
bone density in patients with structurally flawed bone
and in minimizing morbidity and mortality by prevent-
ing fractures. Furthermore, they appear to be cost effi-
cient and safe for short-term use in humans. While oral
bisphosphonates may increase the risk for gastrointesti-
nal complications such as esophagitis, adhering to the
3
Bisphosphonates

Table 1
Dosages of Bisphosphonates and Costs* in Selected Conditions

Condition Etidronate Alendronate Risedronate Pamidronate Zolendronate Tiludronate

Osteoporosis 400 mg/d 10 mg/d or 5 mg/d 30 mg q 3 mo 4 mg/yr N/A

treatment† × 14 d q 3 mo 70 mg/wk or 35 mg/wk ($1,155.00)‡ ($988.99)‡
(cost/yr) ($432.88)‡ ($919.08§) ($871.08§)
Osteoporosis N/A — 35 mg/wk N/A N/A N/A
prevention
Paget’s disease 400 mg/d 40 mg/d 30 mg/d 90 mg ($866.25), N/A 400 mg/d
(treatment course) × 6 mo × 6 mo × 2 mo then 30 mg × 3 mo
($1,391.88) ($1,181.94) ($1,047.98) q 3 mo ($288.75) ($1,185.97)
Bone metastases N/A N/A — 90 mg q 4 wk 4 mg q 3-4 wk N/A
Hypercalcemia 7.5 mg/kg/ 15 mg N/A 90 mg PRN Single 4-mg N/A
of malignancy d×3d doses PRN
Fibrous dysplasia N/A 70 mg/wk‡ll N/A 60-90 mg q 2 moll N/A N/A

* Costs at a large chain discount suburban pharmacy in Stamford, CT, December 2002. Does not include dispensing fee.
† For postmenopausal women, men, and glucocorticoid-induced.
‡ Off-label use in the United States
§ Once-weekly dose
ll Until N-telopeptide plateaus
N/A = not applicable

specific instructions as well as switching to a once-week- used off-label in osteoporotic patients unable to tolerate
ly dose may minimize the risk. Intravenous bisphospho- oral bisphosphonates. Bisphosphonates are the agent of
nates are appropriate in patients with Paget’s disease choice for the treatment of osteoporosis and Paget’s dis-
and metastatic osteolytic bone metastases and are being ease.

References
1. Black DM, Cummings SR, Karpf DB, et al: Randomised trial
of effect of alendronate on risk of fracture in women with
existing vertebral fractures. Lancet 1996;348:1535-1541.
2. Black DM, Thompson DE, Bauer DC, et al: Fracture risk reduc-
tion with alendronate in women with osteoporosis: The Fracture
Intervention Trial. J Clin Endocrinol Metab 2000;85:4118-4124.
3. Fogelman I, Ribot C, Smith R, Ethgen D, Sod E, Reginster J-Y:
Risedronate reverses bone loss in postmenopausal women with
low bone mass: Results from a multinational, double-blind,
placebo-controlled trial. J Clin Endocrinol Metab 2000;85:1895-
1900.
4. Harris ST, Watts NB, Genant HK, et al: Effects of risedronate
treatment on vertebral and nonvertebral fractures in women
with postmenopausal osteoporosis: A randomized controlled
trial. JAMA 1999;282:1344-1352.
5. Peretz A, Body JJ, Dumon JC, et al: Cyclical pamidronate infu-
sions in postmenopausal osteoporosis. Maturitas 1996;25:69-75.
6. Guttmann G, Van Linthoudt D: Efficacy of intravenous
pamidronate in osteoporosis, mineralometric evaluation
[French]. Schweiz Rundsch Med Prax 1999;88:2057-2060.
7. Reid IR, Brown JP, Burckhardt P, et al: Intravenous zoledronic
acid in postmenopausal women with low bone mineral density.
N Engl J Med 2002;346:653-661.
8. Fraser WD, Stamp TC, Creek RA, Sawyer JP, Picot C: A double-
blind, multicentre, placebo-controlled study of tiludronate in
Paget’s disease of bone. Postgrad Med J 1997;73:496-502.
9. Berenson JR, Hillner BE, Kyle RA, et al: American Society of
Clinical Oncology clinical practice guidelines: The role of bisphos-
phonates in multiple myeloma. J Clin Oncol 2002;20:3719-3736.
10. Pavlakis N, Stockler M: Bisphosphonates for breast cancer.
Cochrane Database Syst Rev 2002;1:CD003474.
11. Lipton A, Small E, Saad F, et al: The new bisphosphonate,
Zometa (zoledronic acid), decreases skeletal complications in
both osteolytic and osteoblastic lesions: A comparison to
pamidronate. Cancer Invest 2002;20(suppl 2):45-54.
12. Lane JM, Khan SN, O’Connor WJ, et al: Bisphosphonate therapy
in fibrous dysplasia. Clin Orthop 2001;382:6-12.
13. Fleisch H: Can bisphosphonates be given to patients with
fractures? J Bone Miner Res 2001;16:437-440.
14. Peter CP, Cook WO, Nunamaker DM, Provost MT, Seedor JG,
Rodan GA: Effect of alendronate on fracture healing and bone
remodeling in dogs. J Orthop Res 1996;14:74-79.

4 Journal of the American Academy of Orthopaedic Surgeons

 “10”
As the Journal of the American Academy of Orthopaedic
Surgeons enters its second decade of publication with
volume 11, issue 1, I would like to spend a moment
reflecting on the achievements of the last decade and
the potential for progress during the next. JAAOS grew
out of the foresight of the Board of Directors of the
Academy, who saw a need for another means of provid-
ing educational material to orthopaedic surgeons and
those interested in the care of musculoskeletal condi-
tions. The developments in orthopaedic surgery as well
as the breadth and volume of written material had
expanded exponentially. This made it very difficult to
be able to read all of the new material on any given
topic, let alone in the entire field of orthopaedic surgery.
The authors of articles in JAAOS were therefore directed
to evaluate the primary source material available on a
topic and construct a review that selected the most cred-
ible material and emphasized the important concepts.
With appropriate selection of the breadth of the topic,
this approach allowed the readers, within a succinct 10-
page review, to update their knowledge, understand the
limitations of the primary source material, and, if de-
sired, pursue a point of interest in an article from the list
of references.
Since the initial issue of JAAOS in 1993, both the field
of musculoskeletal care and the way we learn about
new developments have continued to evolve rapidly.
The editorial board has reacted to changes in both areas
to continue to make JAAOS relevant for the readership.
New formats have made the Journal more accessible to
all of its readers, no matter their preference. In 1997, the
CD-ROM version was developed and has been updated
annually so that readers can have all of the material
available on any computer. The advent of the JAAOS
website allowed immediate access to even the most cur-
rent issue. It now provides enhanced search capabilities
and abstracts of the articles in seven languages. The
PDA version is being introduced this year at the Annual
Meeting of the American Academy of Orthopaedic
Surgeons in New Orleans. Subscribers will be able to
download single articles or entire issues of JAAOS to
view on their handheld devices.
The approach to the editorial content also has
changed, with new types of review articles that cover
the expanding realm of information on musculoskeletal
conditions. Perspectives on Modern Orthopaedics deals
with innovations in treatment or diagnosis about which
the material defining the effectiveness is often prelimi-
nary or incomplete, and thus not suitable for a full-
Vol 11, No 1, January/February 2003
length submission. The series of articles developed in
conjunction with the Orthopaedic Research Society
gives a glimpse of possibilities for the future, defining
how the research advances of today may translate into
improved treatment tomorrow. Advances in Thera-
peutics and Diagnostics provides the clinician with a
brief summary of how certain pharmaceuticals or diag-
nostic modalities are useful specifically in the evalua-
tion or treatment of musculoskeletal problems.
“10” is also a digital representation of data: zeroes
and ones. The newest section added to JAAOS, which
appears in this issue, is Web and Wireless Review. The
initial topic is websites that deal with software for the
electronic medical office. In each subsequent issue, this
section will review a specific type of website, a utility for
your computer or PDA, an online textbook, or other
applications relevant to the orthopaedic surgeon. Web
addresses for each site discussed will be included, and
direct links will be available in the article on the JAAOS
website at www.jaaos.org. For those who are comfort-
able with these applications, we hope the columns by
our knowledgeable reviewers will help you assess the
quality of a site and its applicability. For those who are
less facile, perhaps both the reviews and the easy acces-
sibility will introduce you to new options for enhancing
your knowledge and practice. We know from our most
recent reader survey that use of the JAAOS website has
increased markedly in the last 2 years, and we will con-
tinue to add features to enhance its value.
Finally, we would like to thank so many of you for
participating in our latest reader survey. We appreciate
both your input as well as the high regard you have for
the Journal of the American Academy of Orthopaedic
Surgeons as a critical element in your continuing educa-
tion. None of this would have been possible without the
dedicated staff in the Journal office in Chicago during the
last 10 years. Each individual has contributed something
unique to the development of JAAOS. The quality of the
editorial content is a direct reflection of the efforts of my
predecessor, John Frymoyer, MD, the talented associate
editors, the many dedicated reviewers, and certainly
those of you who have given of your time to write the
articles that are the core of the success of JAAOS. You all
truly rate a “10,” and with your continued support, the
next decade of JAAOS will be similarly successful.
Alan M. Levine, MD
Editor-in-Chief
5
 Rheumatoid Arthritis of the Shoulder

Andrew L. Chen, MD, MS, Thomas N. Joseph, MD, and Joseph D. Zuckerman, MD

Abstract

Rheumatoid arthritis affecting the shoulder region is a progressive disorder wrist, and elbow usually are in-
that results in pain, loss of range of motion, and functional disability. The volved later. Particularly in the
inflammatory response, which is of unknown etiology, results in synovitis, early phases of the disease, the clini-
pannus formation, and articular destruction. Even when patient history and cal course may be characterized by
physical examination suggest rheumatoid involvement of the shoulder, labora- quiescence during periods of remis-
tory assessment and radiographic evaluation often are necessary to establish sion.
the diagnosis. Nonsurgical management is the primary treatment, including Rheumatoid involvement of the
pharmacologic and physical therapy regimens for patients with mild symp- shoulder may present with an in-
toms and functional disability. Surgical intervention is indicated in patients sidious onset of pain, swelling, and
with significant pain and functional limitation when nonsurgical treatment progressive loss of motion, reflect-
fails to provide relief. The procedure selected depends on careful assessment of ing both articular and periarticular
the degree of articular cartilage injury and compromise of the periarticular involvement. Patients often are
soft tissues. unaware of the early loss of motion,
J Am Acad Orthop Surg 2003;11:12-24 perhaps because of their ability to
compensate with motion at adjacent
joints or with the contralateral ex-
tremity. As motion loss progresses,
Rheumatoid arthritis (RA) is a chronic, and collagen. The release of inflam- the patient may find it difficult to
systemic inflammatory disorder of matory cytokines results in contin- reach previously accessible objects
unclear etiology characterized by an ued cartilage damage, bone erosion, on high shelves or to perform activi-
erosive, symmetrical polyarthritis and soft-tissue degradation, often ties behind the back, such as fasten-
that may lead to progressive disabil- involving the insertion of the rotator ing a brassiere or obtaining objects
ity. The estimated prevalence is 1% cuff. In addition, through poorly from a back pocket. RA may affect
worldwide, with a female-to-male understood mechanisms, chondro- all of the synovial joints of the
ratio of 3:1 that diminishes with age. cytes themselves may play a role in shoulder region—the glenohumeral,
The prevalence increases starting in articular destruction through possi- acromioclavicular, and sternoclavic-
the third decade of life; RA affects ble participation in proteolytic
more than 5% of the population digestion of cartilage matrix.3,4
older than 70 years. Approximately
91% of patients with long-standing Dr. Chen is Chief Resident, Department of
RA (>5 years’ duration) develop Clinical Course Orthopaedic Surgery, New York University–
Hospital for Joint Diseases, New York, NY.
shoulder symptoms.1,2
Dr. Joseph is Chief Resident, Department of
Rheumatoid disease causes a The initial presentation of RA is Orthopaedic Surgery, New York University–
microvascular injury and mild syn- highly variable; however, more than Hospital for Joint Diseases. Dr. Zuckerman is
ovial cell proliferation, with perivas- 90% of patients report generalized Professor and Chairman, Department of Ortho-
cular lymphocytosis. The continued symptoms of fatigue, musculoskele- paedic Surgery, New York University–Hospital
for Joint Diseases.
inflammation results in the forma- tal pain, variable fever, and weight
tion of an erosive, hyperplastic syn- loss.1,2 Some may present with joint
Reprint requests: Dr. Zuckerman, 301 East
ovium (pannus) as well as joint pain alone, which may be monoar- 17th Street, New York, NY 10003.
swelling (Fig. 1). Immune complex ticular or polyarticular without sys-
deposition and complement activa- temic findings. Early involvement Copyright 2003 by the American Academy of
tion on the articular surfaces pro- typically affects the small joints of Orthopaedic Surgeons.
duce degradation of proteoglycans the hand and foot. The knee, ankle,

12 Journal of the American Academy of Orthopaedic Surgeons


a b
Figure 1 Low-power photomicrograph of pannus (a) eroding through articular cartilage
(b), with invasion and destruction of subchondral bone (c) (hematoxylin-eosin, original
magnification ×100).
ular joints. The scapulothoracic
articulation (not a true synovial
joint) may become secondarily
affected as the involvement of adja-
cent joints progresses. Rheumatoid
involvement of the shoulder often is
associated with soft-tissue patholo-
gy. Seventy-five percent of patients
with RA of the shoulder eventually
have rotator cuff compromise, with
20% to 35% developing full-thick-
ness tears.5
Evaluation
Physical Examination
Subcutaneous rheumatoid nod-
ules may be present over the elbow,
forearm, Achilles tendon, or other
joints. Rales on inspiration or rubs
with chest excursion may indicate
pleuritis, pleural effusion, or pericar-
dial effusion. Generalized swelling
and warmth of the affected joint, with
a variably sized effusion, are com-
mon findings. Range of motion may
be diminished because of swelling
Vol 11, No 1, January/February 2003
Andrew L. Chen, MD, MS, et al
vicular joints suggests involvement,
as do warmth and swelling.
Subacromial or subdeltoid bursi-
c
tis may occur in the absence of sig-
nificant articular destruction and
causes local pain and swelling.
Bursitis may limit motion but will
not cause fixed contractures, as
seen with joint involvement.
Laboratory Evaluation
Patients without a history of RA
should have a complete work-up for
inflammatory or autoimmune etiolo-
gies (Table 1). Further testing,
including HLA typing or serum pro-
tein characterization, generally is
unnecessary during the initial stages
of evaluation but may be done once
the diagnosis of RA has been sug-
gested.
Sterile aspiration of the gleno-
humeral joint may help differentiate
RA of the shoulder from other eti-
ologies. This is especially important
in a patient with an inflamed,
and pain secondary to synovitis and
capsular distension.
The patient with shoulder in-
volvement typically holds the
extremity at the side in a protective
position. Initially, active motion
may be limited by pain while pas-
sive motion is unaffected. As the
process progresses, both active and
passive motion become limited,
leading to fixed contractures in all
three important planes of motion—
forward elevation, external rotation,
and internal rotation. Muscle atro-
phy occurs as a result of rotator cuff
involvement as well as disuse (Fig.
2). With progressive articular and
osseous glenohumeral disease,
painful crepitus will be evident.
The glenohumeral joint is symp-
tomatic without associated acromio-
clavicular or sternoclavicular in-
volvement in two thirds of cases.1
Painful cross-chest adduction is Figure 2 Atrophy of the shoulder girdle
nonspecific and can indicate either musculature, as well as subdeltoid/sub-
acromial swelling, are evident in this
glenohumeral or acromioclavicular patient with advanced rheumatoid disease
disease. Tenderness to palpation of of the shoulder.
the acromioclavicular or sternocla-
13
Rheumatoid Arthritis of the Shoulder

Glenoid erosions can be central or

Table 1
Laboratory Profile of a Patient With Rheumatoid Arthritis
Test
Complete blood cell count
Erythrocyte sedimentation rate
Serum immunoglobulins, immune
complexes, cryoglobulins
Antinuclear antibody titer
Anti-DNA, anti-ENA (nonhistone
nuclear antigens) antibodies
Serum complement
Rheumatoid factor
ENA = extractable nuclear antigen
warm, tender shoulder in whom
septic arthritis must be ruled out,
particularly in the presence of a
fever (Table 2).
Radiographic Evaluation
The earliest radiographic sign of
rheumatoid involvement of the
glenohumeral articulation is re-
gional osteopenia of the humeral
head or glenoid (Fig. 3, A). With
disease progression, marginal ero-
Result
Normocytic, normochromic
anemia without leukocytosis
Elevated
Elevated
Variable
Negative
Negative
Positive in 75% of patients
sions and cysts become apparent at
the inferior margin of the humeral
head, with subsequent involvement
of the glenoid (Fig. 3, B). Humeral
head erosions may be evident ini-
tially at the articular margins, at
sites of soft-tissue insertion where
inflammation is greatest (Fig. 3, C).
These erosions may progress to
involve large portions of the head,
eventually resulting in areas of bone
loss or even flattening of the head.
peripheral. Superior migration of
the humeral head may occur as a
result of involvement of the rotator
cuff, with eventual pseudoarticula-
tion between the humeral head and
the acromion process and erosion of
the undersurface of the acromion
extending into the acromioclavicu-
lar joint1,6,7 (Fig. 3, D). Although less
commonly encountered, extensive
destructive arthritis, or arthritis
mutilans, can occur. Sclerosis is un-
common and usually reflects a later
stage after the inflammatory com-
ponent has subsided and secondary
degenerative arthritis develops.
Acromioclavicular involvement is a
continuum, from subchondral
osteopenia to marginal erosions to
extensive osteolysis.
Magnetic resonance imaging
(MRI) is useful for demonstrating
osseous, articular, and soft-tissue
changes. Joint effusion, synovial
inflammation, pannus formation,
and capsular distension can be iden-
tified. The extent of rotator cuff
involvement may be determined,
ranging from inflammation to atten-
uation to extensive, full-thickness
compromise. MRI is especially use-
ful for the evaluation of shoulder

Table 2
Comparison of Synovial Fluid Aspirates

Synovial Fluid
Characteristic Rheumatoid Arthritis Osteoarthritis Septic Arthritis

Volume Increased Slightly increased Increased

Color Clear to turbid, yellow-green Clear, yellow Turbid to grossly purulent
Viscosity Low High Low
Mucin clotting Fair to poor Normal Variable
White blood cells 15,000-20,000/mL, with 0-2,000/mL, with >100,000/mL, with
60% to 70% neutrophils <25% neutrophils >75% neutrophils
Glucose <25% serum glucose level Equivalent to serum glucose level <50% serum glucose level
Protein Normal to increased Normal Increased
Other Variable cholesterol crystals, — Gram stain may reveal
low complement pathogens

14 Journal of the American Academy of Orthopaedic Surgeons

 Andrew L. Chen, MD, MS, et al

Crystalline arthropathies of the

shoulder can have presentations
similar to that of RA. An insidious
onset of mild shoulder discomfort
with low-grade inflammation
accompanied by blood-tinged syn-
ovial fluid replete with debris,
hydroxyapatite crystals, and few
inflammatory cells (mostly mono-
cytes) is indicative of Milwaukee
shoulder (calcium hydroxyapatite
A B crystalline arthropathy). Positive
staining of crystals with alizarin red
S confirms the diagnosis. Both gout
(sodium urate crystal deposition)
and pseudogout (calcium pyrophos-
phate dihydrate crystal deposition)
may have articular cartilage calcifi-
cations but may be differentiated on
synovial fluid examination; calcium
pyrophosphate dihydrate deposition
has positively birefringent rhom-
boid-shaped crystals, while gout has
negatively birefringent needle-
C D shaped crystals.5,10,11
Osteoarthritis is the most com-
Figure 3 A, Anteroposterior radiograph showing early changes of rheumatoid disease.
Osteopenia, with minimal articular degenerative changes, and superior migration of the mon form of glenohumeral arthritis,
humeral head consistent with rotator cuff compromise are present. B, Intermediate affecting up to 80% to 85% of women
changes of symmetric glenohumeral joint space loss and early cyst formation. C, As the older than 70 years.12 Osteoarthritis
disease progresses, more extensive erosions are evident about the humeral head and gle-
noid; progressive glenoid bone loss results in medialization of the humeral head. The may be secondary to trauma or frac-
superior migration of the humeral head indicates progressive rotator cuff deterioration. ture, developmental dysplasia, or
D, Extensive articular destruction, or arthritis mutilans, reflects end-stage changes with old sepsis, or may be a manifestation
extensive erosions and bone loss.
of “burned out” inflammatory arthri-
tis. Its characteristic radiographic
presentation shows asymmetric joint
space narrowing, subchondral scle-
weakness and pain not fully ex- Differential Diagnosis rosis, and osteophytes about the glen-
plained by bony changes seen on Although RA is the most com- oid and humeral head (Fig. 5).
plain radiography.8 mon inflammatory arthritis to
Computed tomography (CT) affect the shoulder, its variable,
may be indicated when preopera- nonspecific presentation may re- Classification
tive analysis of humeral head quire that other conditions be
defects and glenoid articular ero- excluded before the diagnosis can The Laine classification of RA of the
sions is necessary. Albertsen et al9 be established. Glenohumeral aspi- glenohumeral articulation has three
reported agreement between preop- ration is often helpful (Table 2). stages based on clinical and radio-
erative CT results and intraopera- Patients with septic arthritis often graphic findings.13 In stage I, slight
tive findings, concluding that CT have high fever and local findings limitation of shoulder motion is pres-
could characterize osseous defects of erythema and swelling. Rotator ent, with mild to moderate pain and
and bone loss more accurately than cuff arthroplasty may be associated tenderness to palpation. Crepi-
can standard radiography (Fig. 4). with anterosuperior instability and tation may be appreciated on range
This is particularly important in superior humeral migration, often of motion. Radiographs show only
evaluating glenoid erosion to deter- with secondary erosive changes on generalized osteopenia. Stage II is
mine whether implantation of a gle- the inferior aspect of the acromion characterized by moderate limita-
noid component is possible. and the acromioclavicular joint. tion of shoulder motion, moderate

Vol 11, No 1, January/February 2003 15

Rheumatoid Arthritis of the Shoulder
A B
Figure 4 Axial CT views of the shoulder. A, Early involvement, with joint space narrowing (arrows) but maintenance of glenoid mor-
phology. B, Later-stage changes showing significant glenoid bone loss and erosion (arrows) into the glenoid neck. C, Advanced changes,
with extensive erosion (arrows) of the glenoid and humeral head.
to severe pain, and crepitus. Radio-
graphic findings include osteopenia,
erosive bony changes, and joint
space narrowing. In stage III, severe
functional deficits are present; range
of motion is painful and limits activ-
ities of daily living. Radiographs
show advanced erosive changes of
the humeral head and glenoid. 13
Neer14 classified RA of the shoulder
into three categories based on clini-
cal and radiographic findings; his
dry, wet, and resorptive stages are
approximately equivalent to those
of Laine et al.13
Nonsurgical Management
Nonsurgical management of the
rheumatoid shoulder is indicated
for mild to moderate (stage I) dis-
ease, when synovial inflammation is
the primary manifestation before
significant bony changes occur. The
emphasis is on optimal use of med-
ications (Fig. 6).
Intra-articular Corticosteroid
Injection
Intra-articular injection of corti-
costeroids for RA of the shoulder
has been described for the treat-
ment of acute and subacute inflam-
matory synovitis. Although the
intra-articular administration of
16
C
corticosteroids often may result in lution of the acute episode, therapy
dramatic symptomatic relief, it can progress to include more rigor-
should be considered as only a ous strengthening and stretching to
temporizing measure for patients regain full range of motion. Ideally,
who have not responded to oral exercises should be performed five
medications. Multiple injections times a day in 10-minute sessions
can have a deleterious effect on rather than in one or two long ses-
connective tissue structures, in- sions.
cluding the articular cartilage and
the rotator cuff tendons, and there-
fore should be avoided.1,15 Most
physicians suggest limiting injec-
tions to three and to consider re-
peat injections only when signifi-
cant improvement has resulted
from the previous injection.
Physical Therapy
Maintenance and/or improve-
ment of shoulder motion may be
enhanced by physical therapy con-
sisting of passive and active-assisted
range-of-motion exercises. During
periods of active synovitis, motion
should be maintained with assisted
and passive motion exercises focus-
ing on forward elevation, external
rotation, and internal rotation be-
hind the back. As the synovitis and
inflammation improve, stretching
Figure 5 Anteroposterior radiograph of an
can be initiated to improve the over- osteoarthritic glenohumeral joint shows
all range of motion. Isometric exer- subchondral sclerosis, cyst formation,
cises for the deltoid muscle and humeral head flattening, and osteophyte
formation. This classic appearance is readily
rotator cuff can effectively maintain distinguishable from the radiographic
muscle tone and strength during changes typical of RA (Figure 3).
periods of exacerbation. With reso-
Journal of the American Academy of Orthopaedic Surgeons
 Andrew L. Chen, MD, MS, et al

ever, staging also depends on the

Signs and symptoms nature of the procedures (eg, arthro-
Pain scopic or open). Given equal symp-
Erythema
Swelling tomatology, opinions vary regard-
Loss of range of motion ing prioritization of upper versus
lower extremity. When shoulder
surgery is done first, lower extremi-
Moderate-Severe ty procedures should be delayed at
Mild least 3 months to avoid weight bear-
Minimal or no Mild to severe
ing on the recovering shoulder.
radiographic changes radiographic changes This period may be extended to
more than 6 months to allow heal-
Failure/ ing of additional soft-tissue proce-
Nonsurgical treatment progression Surgical
Activity modification treatment dures such as rotator cuff repair.
Medications When the lower extremity is ad-
NSAIDs
Disease-modifying drugs
Mild to moderate dressed first, shoulder surgery
radiographic changes
Antimetabolics should be delayed until assistive
Oral corticosteroids
Physical therapy
Severe ambulatory devices are no longer
radiographic
Intra-articular corticosteroid injection Cartilage-preserving
changes
necessary.
Synovectomy
Débridement
When multiple upper extremity
procedures are necessary, the most
symptomatic joint should be ad-
dressed first. In general, prioritiza-
Cartilage-sacrificing
Prosthetic replacement tion should be given to the proce-
dure that results in the greatest func-
tional improvement. Neer et al17
Symptomatic
Hemiarthroplasty Total shoulder arthroplasty
maintained that hand or wrist
improvement
Primary humeral head involvement Humeral and glenoid involvement involvement should be addressed
Irreparable rotator cuff tear Rotator cuff intact or reparable before ipsilateral elbow or shoulder
Inadequate glenoid bone stock for Adequate glenoid bone stock
total shoulder arthroplasty disease because functional limita-
tions of the hand or wrist may pre-
clude rehabilitation of the elbow or
shoulder due to a lack of incentive to
Observation Rehabilitation
use the involved upper extremity.
Friedman and Ewald18 stated that
Figure 6 Algorithm for treatment of RA of the shoulder.
the elbow should be addressed
first; giving priority to surgical
management of the elbow yields
Surgical Management methods such as synovectomy. greater subjective and objective
Cartilage-sacrificing procedures (eg, functional improvement of the up-
Surgical management of the rheu- hemiarthroplasty, total shoulder per limb and allows for a longer
matoid shoulder is indicated when arthroplasty, and arthrodesis) are interval between arthroplasties.
medications and physical therapy indicated when articular cartilage Gill et al19 reported that arthroplas-
are no longer effective in relieving loss is extensive and beyond preser- ty of both the shoulder and elbow
pain and maintaining function. vation. for end-stage RA may be done
Selection of procedure is based on successfully independent of the
a careful assessment of the degree Basic Principles sequence of joint replacements.
of involvement of the articular car- With multiple upper extremity in-
tilage, subchondral bone, and peri- Staging of Procedures volvement, technical considerations
articular soft tissues. Cartilage-pre- The polyarticular nature of RA such as humeral component stem
serving procedures are indicated often necessitates multiple surgical length in shoulder or elbow arthro-
when some articular cartilage re- procedures. Most authors agree plasty also must be taken into ac-
mains intact and the goal is to pre- that the most disabling articulation count in anticipation of future pro-
vent or slow disease progression by should be addressed first;16-19 how- cedures.

Vol 11, No 1, January/February 2003 17

Rheumatoid Arthritis of the Shoulder
Timing
The timing of surgical manage-
ment should be dictated by the
degree of symptoms and the clini-
cal presentation. Early surgical in-
tervention with synovectomy or
bursectomy may be indicated for
patients with only a diminished
range of motion or a decreased
subacromial space. Surgical inter-
vention also may be based on the
degree of bone loss rather than just
pain and disability because further
disease progression could preclude
later reconstructive surgery.
Systemic Considerations
The systemic nature of RA re-
quires careful multidisciplinary
assessment before surgery. The cer-
vical spine must be evaluated for
stability before endotracheal intuba-
tion. Subtle myelopathy secondary
to cord compression from C1-C2
instability may be mistaken for dif-
fuse joint involvement resulting in
weakness. Of particular concern are
the possible need for perioperative
corticosteroids, the increased risk of
infection because of immunosup-
pression, and perioperative anemia.
Cartilage-Preserving Procedures
Bursectomy and/or synovectomy
is indicated for patients with primar-
ily active synovitis without evidence
of extensive articular destruction.
Although joint débridement may
provide symptomatic relief in pa-
tients with soft-tissue swelling and
evidence of inflammation, it seldom
results in a significant increase in
range of motion. 20 Synovectomy
also may be done in patients with
rapidly progressing synovitis in an
effort to slow disease progression.
However, the results of synovecto-
my generally depend on the degree
of articular cartilage involvement;
the best results are obtained in
patients with early (stage I) disease.1
Synovectomy may be either open or
arthroscopic, with successful return
to pain-free motion in up to 80% of
18
patients. 21 Arthroscopic gleno-
humeral synovectomy and subacro-
mial bursectomy appear to allow
early return to function. Acromio-
plasty or coracoacromial ligament
release is generally not done in
patients with RA because doing so
could compromise the coracoacro-
mial arch and may lead to antero-
superior instability, particularly in
patients with rotator cuff dys-
function.
Cartilage-Sacrificing Procedures
When either nonsurgical man-
agement or cartilage-preserving
procedures fail to provide adequate
relief, prosthetic replacement is
indicated for patients with unremit-
ting or progressive pain and func-
tional limitation. Approximately
20% to 35% of patients who require
prosthetic replacement have con-
comitant rotator cuff tears; these
may be addressed at the time of
arthroplasty, necessitating a modifi-
cation of the postoperative course.
Rozing and Brand22 examined the
results of rotator cuff repair at the
time of shoulder arthroplasty for
RA and concluded that concomitant
cuff repair significantly (P = 0.002)
improved postoperative clinical
shoulder scores compared with
patients in whom tears were not
repaired.
The modular humeral compo-
nents are available in a range of
stem sizes and humeral heads. The
varying stem sizes enable secure fix-
ation both with and without cement.
Cement fixation is more often used
in rheumatoid patients because of
the poor bone quality and proximal
bone loss. Humeral heads are avail-
able in varying neck lengths and
diameters, allowing improved soft-
tissue balancing that enhances the
stability of the implant. Asymmetric
humeral heads are used to modify
offset as well as to change the orien-
tation of the component. These
modifications are designed to im-
prove soft-tissue balancing and the
Journal of the American Academy of Orthopaedic Surgeons
stability of the articulation. Famili-
arity with the components of the
system allows the surgeon to opti-
mize fixation, making a stable, func-
tional articulation more likely.
A range of shoulder implant sys-
tems is available. Most use an all-
polyethylene glenoid component;
metal-backed components are no
longer common. The glenoid com-
ponent is designed for cement fixa-
tion, with a keel or multiple pegs for
insertion into the glenoid.
Hemiarthroplasty
Indications for proximal humeral
replacement (shoulder hemiarthro-
plasty) include extensive humeral
head involvement with minimal or
no involvement of the glenoid artic-
ular surface (uncommon in the
rheumatoid shoulder); extensive
humeral head and glenoid involve-
ment with associated osteopenia
and/or bone loss, such that secure
fixation of the glenoid component is
unattainable; and extensive articular
cartilage deterioration in the pres-
ence of a massive, irreparable rotator
cuff tear. In younger patients (<65
years) who wish to maintain an
active lifestyle, concerns about gle-
noid component loosening have led
some to avoid the use of glenoid
components. However, long-term
pain relief is less reliable than with
glenoid resurfacing, and continued
degeneration of the glenoid can
result in progressive symptoms.23,24
The procedure is done with the
patient in a beach-chair position,
using an anterior deltopectoral
approach. During the exposure,
soft tissues are handled carefully as
they may often be attenuated. The
subscapularis tendon and under-
lying capsule are divided 1 cm
medial to the insertion on the lesser
tuberosity. There may be significant
contracture of the anterior soft
tissues requiring mobilization of
the subscapularis tendon and the
underlying capsule. This is general-
ly done by releasing the adhesions

of the subscapularis at the base of
the coracoid and along the anterior
glenoid neck. This should allow
significant lateral excursion of the
subscapularis tendon and muscle,
which will enhance postoperative
external rotation. In general, a cir-
cumferential capsular release
around the glenoid margin, freeing
the inferior and posterior capsules,
will mobilize the rotator cuff,
enhancing both intraoperative expo-
sure and postoperative mobility.
After resection of the humeral
head, the glenoid is carefully in-
spected to evaluate the integrity of
the articular cartilage and the pres-
ence and degree of bone loss. Rarely
is the articular cartilage of the gle-
noid sufficiently intact to obviate the
need for resurfacing, particularly
when significant humeral head
changes are present. Therefore, iso-
lateral humeral destruction is not the
common indication for hemiarthro-
plasty in rheumatoid patients. More
often, there is extensive glenoid
bone loss, or the remaining bone is
of insufficient quality to allow
secure fixation of the glenoid com-
ponent. When there is significant
asymmetric glenoid wear, reaming
of the glenoid should be considered
to restore the concavity and thereby
enhance the stability of the prosthet-
ic glenoid articulation. The rotator
cuff also should be carefully in-
spected: irreparable defects of the
supraspinatus, infraspinatus, or
teres minor tendons also preclude
insertion of a glenoid component.
The proximal humeral osteotomy
is performed to place the component
in 25° to 40° of retroversion. Se-
quential reaming of the humeral
shaft determines the appropriate
component size. The decision to
place a cemented or cementless
humeral component generally is
made intraoperatively. Cementless
implantation is acceptable in most
cases. However, in patients with ex-
tensive rheumatoid involvement of
the proximal humerus with large
Vol 11, No 1, January/February 2003
cyst formation, cementing often is
necessary to achieve rotational and
axial stability. A modular implant is
preferable because it provides an
opportunity to adjust the soft-tissue
balancing and enhance stability.
Repair of the subscapularis tendon
is critical. When the closure is com-
plete, the amount of external rota-
tion possible without undue tension
on the subscapularis repair should
be documented to guide the postop-
erative rehabilitation program.
Hemiarthroplasty results in reli-
able pain relief and improvement of
function and range of motion, al-
though the outcome is not as pre-
dictable in patients with RA as in
patients with osteoarthritis.25 This is
thought to be the result of poor bone
stock and compromised soft tissues.
Koorevaar et al26 examined the out-
comes of 19 cases of shoulder hemi-
arthroplasty for RA at a mean of 8
years; 64% of patients reported little
or no pain, and no patient com-
plained of severe pain. Recurrence
of symptoms and functional debili-
tation because of progressive gle-
noid degeneration may necessitate
glenoid resurfacing, primarily in
patients in whom the indication for
hemiarthroplasty was a reasonably
intact glenoid surface.
Total Shoulder Arthroplasty
Total shoulder arthroplasty is in-
dicated for patients with debilitating
pain and end-stage RA of the shoul-
der with extensive humeral head
and glenoid articular cartilage loss,
yet with sufficient bone stock and
soft-tissue integrity to achieve a sta-
ble articulation. The initial exposure
and preparation are the same as for
the patient undergoing hemiarthro-
plasty. Exposure of the glenoid is
obtained by subscapularis mobiliza-
tion and capsular releases. With the
glenoid exposed, the anterior gle-
noid neck is palpated to identify the
direction for preparation of the gle-
noid component fixation. The
glenoid is prepared using a combi-
Andrew L. Chen, MD, MS, et al
nation of drills, reamers, and burrs.
The reaming should provide an
exacting congruency with the back
surface of the glenoid component.
Proper alignment of the reamer will
correct asymmetric glenoid wear
and allow restoration of more
anatomic component orientation.
Proper glenoid preparation is con-
firmed by insertion of a trial compo-
nent. A dry field is obtained for
optimal bone-cement interface, and
the glenoid component is then
cemented in place. The humeral
head component is then inserted, as
described. Appropriate soft-tissue
balancing, which is essential for a
stable articulation, is achieved by a
combination of selective soft-tissue
releases and insertion of appropri-
ately sized prosthetic components
(Fig. 7).
Rotator cuff tears should be re-
paired at the time of total shoulder
arthroplasty. The repair sequence
varies, but generally the extent of
the rotator cuff tear is identified with
the initial exposure. The edges of
the tear are tagged with sutures, and
the rotator cuff is mobilized so that it
can be advanced laterally to its
insertion. After insertion of the gle-
noid component but before insertion
of the humeral component, sutures
are passed through drill holes in the
greater tuberosity that will later be
used for the tendon-to-bone repair.
These sutures are left in place while
the humeral component is inserted.
When the components are in place
and the humeral head is reduced,
the rotator cuff repair is completed
using the previously placed tendon-
to-bone sutures. Any additional
tendon-to-tendon sutures can be
placed, as well. Performing the final
portion of the rotator cuff repair
after implantation of the compo-
nents eliminates the stress on the
repair that would occur if significant
manipulation of the shoulder were
necessary. Occasionally, additional
surgical releases and rotator cuff
mobilization are necessary to allow
19
Rheumatoid Arthritis of the Shoulder

for secure repair to the greater

tuberosity. The coracoacromial liga-
ment usually is not released during
hemiarthroplasty or total shoulder
arthroplasty. When rotator cuff
repair is necessary, the undersurface
of the acromion should be inspect-
ed carefully, but acromioplasty is
rarely necessary. The goal is to
maintain the integrity of the coraco-
acromial arch because of its contri-
bution to glenohumeral stability in
these significantly compromised A B
shoulders.
Several investigators have report-
ed that total shoulder arthroplasty
for end-stage RA results in short-
and long-term pain relief, satisfac-
tory increases in range of motion,
and markedly improved functional
status. 27-29 Because of soft-tissue
compromise and the inflammatory
* *
nature of the disease, the results of
total shoulder arthroplasty in pa-
tients with RA have not been shown
to be as satisfactory or reliable as
those in patients with osteoarthri- C D
tis.25 Despite concerns about proxi-
mal humeral migration and glenoid
radiolucent lines, long-term results
have shown that the degree of pain
relief, range of motion, abduction
force, and functional status do not
diminish significantly over time.30

Postoperative Rehabilitation
The postoperative rehabilitation
regimen must be tailored to the spe-
cific needs of each patient. Design
of the regimen is based on the sur-
geon’s intraoperative assessment of
the quality of the soft tissues, com-
ponent stability, and any associated
repairs. Patients should be coun-
seled that maximum benefit after
prosthetic shoulder replacement
may not be realized until 6 months
to 1 year after surgery.
Rehabilitation begins on the first
postoperative day, with active range
of motion for the ipsilateral hand,
wrist, and elbow, and passive and
active-assisted range of motion for
the shoulder. Initially, this includes
E F
Figure 7 Anteroposterior (A) and axillary (B) radiographs of the left shoulder in a 69-
year-old woman with seropositive RA and debilitating pain for 1 year. T1-weighted coro-
nal (C) and axial (D) magnetic resonance images of the same patient showing attenuation
of the rotator cuff tendon (black arrow) but without a full-thickness tear. The humeral
head erosions (asterisk) are extensive and well delineated. Glenoid bony architecture
(white arrow) indicates that there is probably sufficient bone stock for placement of a gle-
noid component. Anteroposterior (E) and axillary (F) radiographs immediately after total
shoulder arthroplasty.
supine passive forward elevation initial 6 postoperative weeks is
and external rotation exercises with determined by the intraoperative
the arm at the side. The degree of repair of the subscapularis tendon;
external rotation allowed during the in general, 30° to 40° of external rota-

20 Journal of the American Academy of Orthopaedic Surgeons

 Andrew L. Chen, MD, MS, et al

tion may be tolerated without plac-
ing undue tension on the repair. At
approximately 4 to 6 weeks, a more
active shoulder range of motion is
initiated along with internal rotation
behind the back. Isometric strength-
ening exercises are started 4 weeks
after surgery, and resistive strength-
ening exercises usually are initiated
10 to 12 weeks postoperatively when
active range of motion has pro-
gressed.
Complications
Adverse events have been report-
ed in up to 11.0% of total shoulder
arthroplasties and up to 15.7% of
shoulder hemiarthroplasties31 (Table
3). Cofield et al31 categorized com-
plications of shoulder arthroplasty
into four groups: (1) coexisting in-
juries to the shoulder at the time of
surgery, such as rotator cuff tear or
chronic dislocation; (2) problems
with the healing process after sur-
gery, such as failure of subscapularis
tendon healing resulting in anterior
shoulder instability or weakness in
internal rotation, or overexuberant
postoperative fibrosis causing joint
stiffness; (3) complications related to
the general health of the patient,
such as infection secondary to chronic
immunosuppression; and (4) com-
plications associated with joint
arthroplasty, such as periprosthetic
fracture or component loosening.

Table 3
Complications After Total Shoulder Arthroplasty and Shoulder Hemiarthroplasty

Total Shoulder Arthroplasty* Shoulder Hemiarthroplasty†

Complication No. % Complication No. %

Rotator cuff tear 23 1.9 Instability 14 2.8

Instability 18 1.5 Glenoid arthritis 12 2.4
Glenoid loosening 15 1.3 Tuberosity nonunion 9 1.8
Intraoperative fracture 15 1.3 Rotator cuff tear 9 1.8
Component malposition 7 0.6 Nerve injury 8 1.6
Nerve injury 7 0.6 Infection 5 1.0
Infection 5 0.4 Intraoperative fracture 3 0.6
Humeral loosening 4 0.3 Humeral loosening 3 0.6
Postoperative fracture 4 0.3 Wound problem 2 0.4
Wound problem 4 0.3 Tuberosity malposition 2 0.4
Wire breakage 3 0.3 Hematoma 2 0.4
Impingement 3 0.3 Perioperative death 2 0.4
Tuberosity nonunion 3 0.3 Postoperative fracture 1 0.2
Chronic pain, unexplained 3 0.3 Heterotopic ossification 1 0.2
Reflex dystrophy 2 0.2 Impingement 1 0.2
Hematoma 2 0.2 Reflex dystrophy 1 0.2
Component dissociation 2 0.2 Acromioclavicular pain 1 0.2
Extruded cement 2 0.2 Chronic pain, unexplained 1 0.2
Heterotopic ossification 1 0.1 Stiffness 1 0.2
Stiffness 1 0.1 Total 78 15.7‡
Spacer dislocation 1 0.1
Intraoperative death 1 0.1
Pulmonary embolism 1 0.1
Total 127 11.0‡

* 1,183 shoulders in 22 series treated between 1980 and 1999.

† 498 shoulders in 20 series treated between 1980 and 1999.
‡ Percentages given for complications are rounded.
(Adapted with permission from Cofield RH, Chang W, Sperling JW: Complications of shoulder arthroplasty, in Iannotti JP, Williams
GR [eds]: Disorders of the Shoulder: Diagnosis and Management. Philadelphia, PA: Lippincott Williams & Wilkins, 1999, pp 571-593.)

Vol 11, No 1, January/February 2003 21

Rheumatoid Arthritis of the Shoulder
Significant instability after shoul-
der arthroplasty usually is recogniz-
able by physical examination and
radiography and can be related to
improper soft-tissue balancing, rota-
tor cuff disruption, component mal-
position, improper component sizing,
or component loosening. Other fac-
tors associated with instability after
prosthetic replacement of the shoul-
der include older age, chronic preop-
erative shoulder dislocation, and
aberrant glenoid anatomy resulting
from glenoid bone deficiency or
asymmetric wear. Soft-tissue balanc-
ing intraoperatively should allow for
up to 50% translation both anteriorly
and posteriorly. Superior subluxation
of the glenohumeral component is
not necessarily indicative of rotator
cuff disruption; inferior subluxation in
the immediate postoperative period
usually represents deltoid atony but
can indicate inadequate soft-tissue
tensioning, which may require sec-
ondary surgical corrections.
Axillary nerve neurapraxia is the
most common injury. The musculo-
cutaneous nerve may also be injured
during exposure or overzealous
retraction of the conjoined tendon.
Radial nerve palsy also has been
described secondary to cement
extrusion from the canal distally,
especially with revision arthroplasty
or inadvertent humeral cortical pen-
etration. If this finding is noted on
postoperative radiographs, explo-
ration is indicated. Continuity of the
nerve should be confirmed and all
cement removed. In most other
cases of nerve injury, an initial peri-
od of observation is indicated
because most nerve injuries repre-
sent neurapraxia. If neurologic
improvement does not occur within
4 weeks, electromyography should
be done to document the degree of
neurologic injury and assess the
potential for recovery. Exploration
may be indicated for nerve palsies
that do not improve by 12 weeks.
Periprosthetic fractures may occur
intraoperatively or postoperatively.
22
Intraoperative fractures can occur
during humeral shaft preparation or
insertion of the humeral component;
postoperative fractures usually are a
result of trauma. Fractures entirely
distal to the humeral component
may be treated nonsurgically with a
fracture brace. Fractures proximal to
the tip of the stem can be treated by
cerclage wiring, plate fixation com-
bined with cerclage wires, or, for
intraoperative fractures, insertion of
a long-stem component combined
with cerclage wiring.
The risk of infection after pros-
thetic replacement is increased in the
presence of diabetes mellitus, RA,
lupus erythematosus, remote sites of
infection, prior shoulder surgery, or
use of immunosuppressive medica-
tions. Little has been published that
specifically addresses the treatment
of infected shoulder arthroplasty.
For acute or subacute infection (<3
months after prosthetic replace-
ment), open irrigation and débride-
ment, followed by 6 to 8 weeks of
intravenous antibiotics, is usually
adequate. For delayed infection,
component removal and insertion of
antibiotic-impregnated cement is
necessary. Staged reimplantation
may be undertaken after the suc-
cessful eradication of infection, as
documented by normalization of the
white blood cell count, sedimenta-
tion rate, C-reactive protein level,
and intraoperative frozen section.
Prosthetic loosening almost
always involves the glenoid compo-
nent and is best minimized by
careful glenoid preparation with
preservation of bone stock, meticu-
lous cement technique, and close
attention to soft-tissue balancing.
Massive, unreconstructable rotator
cuff tears are a relative contraindica-
tion to glenoid replacement. These
tears underscore the importance of
the rotator cuff in maintaining joint
position and preventing excessive,
eccentric glenoid loading that can
increase the risk of early loosening.
Clinically significant glenoid loosen-
Journal of the American Academy of Orthopaedic Surgeons
ing is uncommon compared with
radiographic findings suggestive of
loosening. Accordingly, it is im-
portant to exclude other causes of
shoulder pain, such as occult infec-
tion or rotator cuff tear. If glenoid
revision is done, removal of the loose
component may reveal a large cen-
tral glenoid defect that may not be
structurally amenable to component
reinsertion, even after bone grafting.
In such cases, impaction grafting
may be done with contouring of the
remaining glenoid bone to a slight
concavity for pseudocongruence
with the humeral head component.
Arthrodesis
Although arthrodesis of the gleno-
humeral joint has been described for
end-stage RA,32 advances in pros-
thetic replacement and surgical tech-
nique have largely supplanted
arthrodesis as the predominant pri-
mary treatment of the end-stage
rheumatoid shoulder. Arthrodesis
of the rheumatoid shoulder should
be undertaken only for selected indi-
cations. These indications include
failed total shoulder arthroplasty or
end-stage involvement with a recent
history of joint sepsis. In these situa-
tions, patients may benefit from
glenohumeral fusion in 30° of abduc-
tion, 30° of forward flexion, and 30°
of internal rotation to allow for hand-
to-mouth and hygiene activities.
Arthrodesis can be done using a vari-
ety of techniques, including screw
fixation or plate-and-screw fixation.
Although plate-and-screw fixation
offers the potential avoidance of post-
operative spica immobilization, the
bone quality in rheumatoid patients
may limit the security of the fixation,
and additional external (spica) immo-
bilization still will be needed postop-
eratively. The utility of shoulder
arthrodesis must be evaluated in the
context of ipsilateral and contralateral
upper extremity involvement.
Acromioclavicular Involvement
Rheumatoid involvement of the

acromioclavicular joint is common,
affecting up to 63% of rheumatoid
patients with painful shoulders.33
It is often adequately addressed
nonsurgically with medications
and corticosteroid injection. How-
ever, persistent or progressively
debilitating pain secondary to
extensive, symptomatic erosions
may necessitate distal clavicular
resection with synovectomy, typi-
cally with successful results. 7
Petersson33 reported acromioclavic-
ular joint resection and subacromi-
al bursectomy to be an effective
procedure at follow-up of 18 to 62
months. Either open or arthroscop-
ic resection of the distal clavicle
may be done. In the setting of RA,
however, resection rarely is per-
formed as an isolated procedure;
more often, it is done at the time of
prosthetic replacement.
References
1. Cuomo F, Greller MJ, Zuckerman JD:
The rheumatoid shoulder. Rheum Dis
Clin North Am 1998;24:67-82.
2. Petersson CJ: Painful shoulders in
patients with rheumatoid arthritis:
Prevalence, clinical and radiological fea-
tures. Scand J Rheumatol 1986;15:275-279.
3. Lipsky PE: Rheumatoid arthritis, in
Wilson JD, Braunwald E, Isselbacher
KJ, et al (eds): Harrison’s Principles of
Internal Medicine, ed 12. New York,
NY: McGraw-Hill, 1991, pp 1437-1442.
4. Shiozawa S, Shiozawa K: A review of
the histopathological evidence on the
pathogenesis of cartilage destruction
in rheumatoid arthritis. Scand J Rheu-
matol Suppl 1988;74:65-72.
5. Curran JF, Ellman MH, Brown NL:
Rheumatologic aspects of painful con-
ditions affecting the shoulder. Clin
Orthop 1983;173:27-37.
6. Cofield RH: Degenerative and arthrit-
ic problems of the glenohumeral joint,
in Rockwood CA Jr, Matsen FA III
(eds): The Shoulder. Philadelphia, PA:
WB Saunders, 1990, pp 678-749.
7. Cruess RL: Rheumatoid arthritis of
the shoulder. Orthop Clin North Am
1980;11:333-342.
8. Kieft GJ, Dijkmans BA, Bloem JL,
Kroon HM: Magnetic resonance imag-
Vol 11, No 1, January/February 2003
Sternoclavicular Involvement
The reported incidence of rheu-
matoid involvement of the sterno-
clavicular joint ranges from 1% to
41%.34 Symptomatology typically is
overshadowed by glenohumeral
involvement and usually responds
to nonsurgical intervention and
intra-articular injections. Recalci-
trant symptoms lasting more than 6
to 12 months may be addressed
with sternoclavicular joint débride-
ment and medial clavicle resec-
tion.34 Care must be taken to pre-
serve the stabilizing ligaments to
avoid complications associated with
sternoclavicular instability.
Summary
Care of the patient with RA of the
shoulder requires a multidisciplin-
ing of the shoulder in patients with
rheumatoid arthritis. Ann Rheum Dis
1990;49:7-11.
9. Albertsen M, Egund N, Jonsson E,
Lidgren L: Assessment at CT of the
rheumatoid shoulder with surgical cor-
relation. Acta Radiol 1994;35:164-168.
10. Ellman MH, Brown NL, Curran JJ:
Shoulder arthritis: Distinguishing
among the many causes of inflamma-
tion. Postgrad Med 1983;73:158-167.
11. Weiss TE, Gum OB, Biundo JJ Jr:
Rheumatic diseases: 1. Differential diag-
nosis. Postgrad Med 1976;60:141-150.
12. Brandt KD, Kovalov-St. John K:
Osteoarthritis, in Wilson JD, Braunwald
E, Isselbacher KJ, et al (eds): Harrison’s
Principles of Internal Medicine, ed 12.
New York, NY: McGraw-Hill, 1991, pp
1475-1479.
13. Laine VAI, Vainio KJ, Pekanmäki K:
Shoulder affections in rheumatoid arthri-
tis. Ann Rheum Dis 1954;13:157-160.
14. Neer CS: The rheumatoid shoulder, in
Crubbs RL, Mitchell NS (eds): The Sur-
gical Management of Rheumatoid Arthritis.
Philadelphia, PA: JB Lippincott, 1971,
pp 117-127.
15. Rozental TD, Sculco TP: Intra-articular
corticosteroids: An updated overview.
Am J Orthop 2000;29:18-23.
Andrew L. Chen, MD, MS, et al
ary approach involving the primary
care provider, rheumatologist,
orthopaedic surgeon, and physi-
cal/occupational therapists. Early
rheumatoid involvement of the
shoulder with minimal articular de-
struction and functional limitations
may be managed nonsurgically
with medications and physical ther-
apy. Advanced rheumatoid disease
of the shoulder with significant pain
and articular destruction may neces-
sitate surgical intervention, ranging
from synovectomy to total shoulder
arthroplasty. Although the results
of prosthetic shoulder replacement
for end-stage RA are not compara-
ble to those achieved for osteo-
arthritis, symptomatic improvement
often is dramatic, with satisfactory
relief of pain, improved range of
motion, and increased functional
ability.
16. Neer CS II: Reconstructive surgery and
rehabilitation of the shoulder, in Kelley
WN, Harris ED Jr, Ruddy S, Sledge CB
(eds): Textbook of Rheumatology, ed 2.
Philadelphia, PA: WB Saunders, 1985,
vol 2, pp 1855-1870.
17. Neer CS II, Watson KC, Stanton FJ:
Recent experience in total shoulder
replacement. J Bone Joint Surg Am
1982;64:319-337.
18. Friedman RJ, Ewald FC: Arthroplasty of
the ipsilateral shoulder and elbow in
patients who have rheumatoid arthritis.
J Bone Joint Surg Am 1987;69:661-666.
19. Gill DR, Cofield RH, Morrey BF:
Ipsilateral total shoulder and elbow
arthroplasties in patients who have
rheumatoid arthritis. J Bone Joint Surg
Am 1999;81:1128-1137.
20. Hess EV: Rheumatoid arthritis: Treat-
ment, in Schumacher HR Jr, Klippel
JH, Robinson DR (eds): Primer on the
Rheumatic Diseases, ed 9. Atlanta, GA:
Arthritis Foundation, 1988, pp 93-96.
21. Petersson CJ: Shoulder surgery in
rheumatoid arthritis. Acta Orthop
Scand 1986;57:222-226.
22. Rozing PM, Brand R: Rotator cuff re-
pair during shoulder arthroplasty in
rheumatoid arthritis. J Arthroplasty
1998;13:311-319.
23
Rheumatoid Arthritis of the Shoulder
23. Cofield RH, Frankle MA, Zuckerman
JD: Humeral head replacement for
glenohumeral arthritis. Semin Arthro-
plasty 1995;6:214-221.
24. Boyd AD Jr, Thomas WH, Scott RD,
Sledge CB, Thornhill TS: Total shoul-
der arthroplasty versus hemiarthro-
plasty: Indications for glenoid resur-
facing. J Arthroplasty 1990;5:329-336.
25. McCoy SR, Warren RF, Bade HA III,
Ranawat CS, Inglis AE: Total shoulder
arthroplasty in rheumatoid arthritis. J
Arthroplasty 1989;4:105-113.
26. Koorevaar RC, Merkies ND, de Waal
Malefijt MC, Teeuwen M, van den
Hoogen FH: Shoulder hemiarthro-
plasty in rheumatoid arthritis: 19 cases
reexamined after 1-17 years. Acta
Orthop Scand 1997;68:243-245.
27. Sojbjerg JO, Frich LH, Johannsen HV,
24
Sneppen O: Late results of total shoul-
der replacement in patients with
rheumatoid arthritis. Clin Orthop
1999;366:39-45.
28. Stewart MP, Kelly IG: Total shoulder
replacement in rheumatoid disease: 7-
to 13-year follow-up of 37 joints. J
Bone Joint Surg Br 1997;79:68-72.
29. Friedman RJ, Thornhill TS, Thomas
WH, Sledge CB: Non-constrained
total shoulder replacement in patients
who have rheumatoid arthritis and
class-IV function. J Bone Joint Surg Am
1989;71:494-498.
30. Sneppen O, Fruensgaard S, Johannsen
HV, Olsen BS, Sojbjerg JO, Andersen
NH: Total shoulder replacement in
rheumatoid arthritis: Proximal migra-
tion and loosening. J Shoulder Elbow
Surg 1996;5:47-52.
Journal of the American Academy of Orthopaedic Surgeons
31. Cofield RH, Chang W, Sperling JW:
Complications of shoulder arthroplasty,
in Iannotti JP, Williams GR (eds):
Disorders of the Shoulder: Diagnosis and
Management. Philadelphia, PA: Lip-
pincott Williams & Wilkins, 1999, pp
571-593.
32. Rybka V, Raunio P, Vainio K: Arthrodesis
of the shoulder in rheumatoid arthri-
tis: A review of forty-one cases. J Bone
Joint Surg Br 1979;61:155-158.
33. Petersson CJ: The acromioclavicular
joint in rheumatoid arthritis. Clin
Orthop 1987;223:86-93.
34. Wirth MA, Rockwood CA Jr: Chronic
conditions of the acromioclavicular and
sternoclavicular joints, in Chapman
MW, Madison M (eds): Operative
Orthopaedics, ed 2. Philadelphia, PA: JB
Lippincott, 1993, vol 2, pp 1673-1693.
 Malignant Bone Tumors:
Limb Sparing Versus Amputation

Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD

Abstract

Amputation, once the mainstay of treatment of malignant bone tumors, now Limb-Sparing Surgery
is used selectively and infrequently. Most patients are candidates for limb- Principles and Guidelines
sparing procedures because of effective chemotherapeutic agents and regi-
mens, improved imaging modalities, and advances in reconstructive There are four basic principles or
surgery. Patient age as well as tumor location and extent of disease help goals of limb-sparing procedures:
define the most appropriate surgical alternatives. Options for skeletal re- (1) Local recurrence should be no
construction include modular endoprostheses, osteoarticular or bulk allo- greater and survival no worse than
grafts, allograft-prosthetic composites, vascularized bone grafts, arthrodesis, with amputation. (2) The proce-
expandable prostheses, rotationplasty, and limb-lengthening techniques. dure, or treatment of its complica-
Two key factors must be considered: survival rates should be no worse than tions, should not delay adjuvant
those associated with amputation, and the reconstructed limb must provide therapy. (3) Reconstruction should
satisfactory function. Functional outcome studies comparing limb-sparing be enduring and not associated with
procedures and amputation have inherent limitations, including the inability a large number of local complica-
to randomize treatment and the subjective nature of important outcome tions requiring secondary proce-
measures. dures and frequent hospitalizations.
J Am Acad Orthop Surg 2003;11:25-37 (4) Function of the limb should
approach that obtained by amputa-
tion, although body image, patient
preference, and lifestyle may influ-
Primary malignant bone tumors are specific treatment strategies and ence the decision.5
rare lesions, with fewer than 3,000 lowering the morbidity rates of Before consideration of limb
new cases per year in the United biopsy and subsequent resection.2,3 preservation, the patient needs to be
States. Before the 1970s, manage- Currently, 80% to 85% of patients appropriately staged and assessed
ment routinely consisted of trans- with primary malignant bone through a multidisciplinary ap-
bone amputations or disarticula- tumors involving the extremities proach. Some elements of the dis-
tions, with dismal survival rates (eg, osteosarcoma, Ewing’s sarco- ease may warrant concern, includ-
(10% to 20%). With the develop- ma, and chondrosarcoma) can be
ment of more effective chemothera- treated safely with wide resection
peutic agents and treatment proto- and limb preservation. Multi-
Dr. DiCaprio is Resident, Department of
cols in the 1970s and 1980s, survival modality therapy has increased
Orthopaedics and Rehabilitation, Yale Univer-
rates improved, which allowed the long-term survival rates of patients sity School of Medicine, New Haven, CT. Dr.
focus of management to shift to with chemotherapy-sensitive tumors Friedlaender is Wayne O. Southwick Professor
limb preservation. 1 Computed to 60% to 70%.1,4 There are a num- and Chair, Department of Orthopaedics and
tomography and magnetic reso- ber of options for skeletal recon- Rehabilitation, Yale University School of
Medicine.
nance imaging (MRI) allow the pre- struction after bone tumor resection,
cise visualization of the anatomic and it is important to compare the
Reprint requests: Dr. DiCaprio, PO Box
location of a tumor and its relation clinical and especially functional 208071, New Haven, CT 06520-8071.
to surrounding structures. Preop- outcomes based on type of recon-
erative planning has been advanced struction, location of the tumor, and Copyright 2003 by the American Academy of
through the use of these modalities, limb-sparing versus ablative sur- Orthopaedic Surgeons.
fostering better patient selection for gery.

Vol 11, No 1, January/February 2003 25

Malignant Bone Tumors: Limb Sparing Versus Amputation
ing relative contraindications to
such procedures (Table 1). Multi-
drug neoadjuvant chemotherapy,
popularized first for patients with
osteosarcoma by Rosen in the late
1970s, is usually initiated as appro-
priate after histologic diagnosis and
staging. Chemotherapy helps con-
trol systemic disease by attacking
micrometastases, dramatically
increasing overall survival rates.1
Neoadjuvant therapy also “steril-
izes” the reactive zone around the
tumor by destroying microscopic
disease at the periphery of the pri-
mary lesion, thus facilitating resec-
tion. Additionally, in some patients
with a relative contraindication to
limb salvage, such as a pathologic
fracture in the upper extremity, the
use of chemotherapy with a favor-
able response may allow limb sal-
vage to be considered. However,
not all malignant bone tumors (and
especially chondrosarcomas) have a
viable and effective chemotherapy
regimen.
When appropriate, after 8 to 12
weeks of preoperative neoadjuvant
chemotherapy, wide tumor resec-
tion is performed to establish local
tumor control. Achieving tumor-
free resection margins is of para-
mount importance and remains the
primary goal in surgical oncology.
Most resections are performed
through an extensile longitudinal
incision, permitting access to the
major neurovascular bundle, with
complete removal of all biopsy
tracts. By definition, a wide resec-
tion will include a cuff of normal tis-
sue surrounding the resected speci-
men. Skeletal defects are large,
averaging 15 to 20 cm, reflecting the
size of these tumors and the need
for negative margins. After recon-
struction, muscle transfers may be
necessary to provide adequate motor
function. Finally, adequate, healthy
soft-tissue coverage is essential to
prevent early wound complications
and subsequent infection. Coverage
may require complex local flaps or
26
Table 1
Relative Contraindications to Limb-Sparing Procedures
Major neurovascular structures encased by tumor when vascular bypass
is not feasible
Pathologic fracture with hematoma violating compartment boundary
Inappropriately performed biopsy or biopsy-site complications
Severe infection in the surgical field
Immature skeletal age with predicted leg-length discrepancy >8 cm
Extensive muscle or soft-tissue involvement
Poor response to preoperative chemotherapy
even free tissue grafts. When in- exists with allograft reconstruction.
dicated on the basis of histologic Longevity, complications, and func-
diagnosis, adjuvant chemotherapy tional outcome vary by anatomic
consisting of multiple agents for site, type of prosthesis, and fixation
synergistic activity is continued for technique.
6 to 12 months after wide tumor
resection. Complications and
After negative tumor margins are Clinical Results
obtained, there is often a large skele- Early complications associated
tal defect requiring reconstruction. with the extensive nature of most
Several options are available.6 Pa- musculoskeletal oncology proce-
tient age, tumor location, and extent dures include wound necrosis/
of disease narrow the list of appro- dehiscence, infection, thromboem-
priate surgical alternatives. bolic disease, neurapraxia, and joint
instability. Meticulous surgical tech-
nique and attention to soft-tissue
Modular Endoprostheses handling and reconstruction can
significantly decrease the frequency
Indications and Advantages of these complications. Late compli-
Currently available metallic pros- cations include aseptic loosening,
thetic systems offer a lightweight, infection, joint or prosthetic insta-
strong, inert means for skeletal bility, fatigue fracture of the pros-
reconstruction. Modularity of pros- thesis, and wear or dissociation of
thetic design allows intraoperative modular components. Late infec-
flexibility based on the final amount tion remains the most serious prob-
of tissue resected. A rigorous reha- lem because most prosthesis-related
bilitation program can be initiated complications can be successfully
immediately after implantation treated with revision surgery. Con-
(usually done with bone cement), cerns include the suboptimal attach-
allowing early joint range of motion ment of soft tissues to the metallic
and weight bearing. Prosthetic components.
reconstruction carries a lower risk of In an attempt to determine pros-
deep infection than do allografts, thesis and extremity survivorship,
and nonunion is not a concern Horowitz et al7 reviewed their expe-
because there are no osteosynthesis rience with 93 prosthetic reconstruc-
sites. Endoprosthetic use also tions over 8 years: 16 proximal
avoids the risk of disease transmis- femur, 61 distal femur, and 16 proxi-
sion and immune responses that mal tibia. Minimum follow-up was
Journal of the American Academy of Orthopaedic Surgeons

24 months (mean, 80 months).
Prosthesis survival at 5 years was
88%, 59%, and 54% for proximal
femur, distal femur, and proximal
tibia reconstructions, respectively.
The overall event-free prosthesis
survival was 63% at 5 years and 36%
at 10 years. Aseptic loosening was
cause for failure in approximately
20% at 5 years and 30% at 10 years.
Limb survival for the entire group
was 87% at 5 years and 81% at 10
years. Patients with lesions of the
proximal tibia had the longest sur-
vival rate, with 93% alive at 10 years.
(Histologies included 11 osteosarco-
mas, 4 malignant fibrous histiocy-
tomas, and 1 chondrosarcoma.) The
group as a whole had a survival rate
of 72% at 10 years and was com-
posed of a variety of histologies,
including 65 osteosarcomas, 13
chondrosarcomas, 10 malignant
fibrous histiocytomas, 3 Ewing’s sar-
comas, and 2 liposarcomas.
Aseptic loosening is the primary
long-term concern with this method
of reconstruction for tumors around
the knee. Whereas allografts success-
fully stabilize after 3 to 5 years, pros-
theses begin to exhibit their inherent
biomechanical limitations after 10
years. For the current rotating-hinge
knee design, reported follow-up is
limited to approximately 10 years.
Malawer and Chou8 in 1995 showed
an 83% survival of prostheses at 5
years and 67% at 10 years. Of 52
patients who survived and were
available at 3-year follow-up, only 10
were available at the 10-year follow-
up. They had a revision rate of 15%,
infection rate of 13%, amputation rate
of 11%, and local recurrence rate of
6%. Overall, 44% of patients had at
least one complication. These sur-
vivorship data are limited because of
the small number of patients but may
represent an improvement from the
simple-hinge, custom-made prosthe-
ses, for which 5-year survival of 80%
drops to 53% at 20 years.7,9-11
Of 1,001 patients treated with
cemented, custom-made endopros-
Vol 11, No 1, January/February 2003
Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD
theses, aseptic loosening was the
principal mode of failure among the
210 requiring revision.10 Seventy-
four revisions (35.2% of those re-
vised) were done for aseptic loosen-
ing. At 10 years, the rates of aseptic
loosening were 6.2%, 32.6%, and
42% for the proximal femur, distal
femur, and proximal tibia, respec-
tively. The poorest prognosis for
prosthesis survival without aseptic
loosening was in young patients
(<20 years) with distal femoral pros-
thetic reconstruction in whom a high
percentage of femur had been re-
placed. Experience to date indicates
that acetabular loosening rates have
been extremely high, simple-hinge
prostheses have a higher loosening
rate than do rotating-hinge designs,
and cemented fixation provides
the lowest rate of loosening.9 Most
loose prostheses can be revised to
improve functioning.
Infection rates range from 0% to
13%.8,9,11 Proximal tibial reconstruc-
tions carry the highest risk of infec-
tion, as do other regions where soft-
tissue coverage is tenuous. Infection
is the most serious complication as-
sociated with limb-sparing proce-
dures and is the most common reason
for amputation after attempted re-
construction. Rates have decreased,
however, with the more common use
of rotational or free flaps now readily
available through microsurgical tech-
niques.
Joint instability is a major concern
in reconstructions about the hip and
shoulder. Dislocation rates for the
hip range from 10% to 15%.7-9,12,13
Reconstruction of the abductor
mechanism and the use of bipolar
components have improved stability
and function.11
Fatigue fracture of intramedul-
lary stems has become extremely
uncommon with the increase in
stem diameters, improvements in
design, and current metallurgy used
during fabrication.11 Dissociation
also is rare with modern prostheses;
most join with Morse tapers.
Regional Considerations
Prosthesis survival for proximal
femoral replacements is generally
reported as 77% to 100% at 10 years,
falling to 57% at 20 years.9,11-13 Poor
abductor muscle function remains a
common reason for decreased func-
tional grades. Zehr et al12 reviewed
their experience with 33 patients
after proximal femoral resection and
reconstruction with an allograft-
prosthetic composite (16 patients) or
a megaprosthesis (17 patients). The
primary mode of failure for compos-
ites was infection, and for megapros-
theses, instability. The 10-year
prosthetic survival rate was 76% for
the composite group and 58% for the
megaprosthetic group. Instability
occurred in 0% and 28% of the com-
posite and megaprosthetic cohorts,
respectively; infection rates were
17% and 6%, respectively. Both
groups functioned well, with 87%
and 80% functional scores for the
respective cohorts. Allograft-pros-
thetic composites have been shown
to have a survival advantage over
megaprostheses used for proximal
femoral reconstructions.12,14
Overall survival of a simple-
hinge distal femoral knee replace-
ment prosthesis at 5, 10, and 20
years is 80%, 65%, and 53%, respec-
tively. 9,10 Functional evaluation
reveals 69% to 93% good to excel-
lent results with less than 10 years
of follow-up.7-11,15 Prosthetic sur-
vival analysis shows that a higher
percentage of femoral bone resected
distally is related to a higher risk of
prosthetic failure.15 The extent of
soft-tissue resection is another im-
portant factor. The most common
cause of failure for distal femoral
prostheses is aseptic loosening. As
length of follow-up increases, the
rate of prosthetic survival diminishes.
Better long-term results are antici-
pated since simple-hinge designs
have given way to modular rotating-
hinge systems (Fig. 1).
Proximal tibial prosthetic replace-
ment survivorship has been poor
27
Malignant Bone Tumors: Limb Sparing Versus Amputation

A B C D

Figure 1 A 16-year-old boy presented with knee pain of 7 months’ duration and a history of bilateral retinoblastoma in infancy.
A, Anteroposterior radiograph of the knee shows an aggressive, eccentric, osteoblastic distal femoral metaphyseal lesion with extensive
periosteal reaction (Codman’s triangle, arrow). Coronal (B) and sagittal (C) T2-weighted MRI scans demonstrate the heterogeneous
lesion, periosteal reaction (white arrow), and soft-tissue extension (black arrow). Open biopsy confirmed the diagnosis of high-grade
osteosarcoma. Treatment included preoperative chemotherapy, wide tumor resection, skeletal reconstruction, and postoperative
chemotherapy. D, Anteroposterior radiograph after distal femoral reconstruction with a modular rotating-hinge knee prosthesis.

because of tenuous soft-tissue cover-
age and unreliable extensor mecha-
nism reconstruction. Survival rates
vary from 45% to 74% at 5 years and
45% to 50% at 10 years.9 Malawer
and Chou 8 found proximal tibial
replacements to have the highest
complication and revision rate
and worst Musculoskeletal Tumor
Society (MSTS) functional scores
(Table 2) for any region reconstruct-
ed. Wound problems and subse-
quent infections have decreased
with the routine use of flaps but
remain frequent problems for recon-
structions in this anatomic site.
Grimer et al 17 reported an initial
infection rate of 36% that was re-
duced to 12% by the use of a medial
gastrocnemius flap. Local recur-
rence was observed in 12.6% of
patients and was associated with
poor response to chemotherapy and
close margins of excision. They also
found that 70% of patients at 10
years required further surgical pro-
cedures and reported a 25% risk of
amputation at 10 years.17
Many designs and techniques are
available for proximal humeral
replacements. The technique of results reported for this site, with in-
Malawer and Chou, 8 including stability the primary reason for poor
implantation of a large-segment functional outcome.7,9,11 O’Connor
prosthesis stabilized by static recon- et al18 reported on 11 patients who
struction with Dacron tape and underwent proximal humeral pros-
dynamic reconstruction by muscle thetic reconstruction. Two demon-
transfers, has yielded the best re- strated evidence of stress shielding,
ported results of any site of pros- six had signs of instability, one had
thetic replacement, with an average a deep infection, and two had ce-
MSTS functional score of 86.7% ramic prosthesis loosening or frac-
(26/30) and no cases of instability. ture. Four of the 11 patients went
However, there is a wide range of on to secondary arthrodesis. Those
Table 2
Musculoskeletal Tumor Society Functional Evaluation16
Lower Extremity Data* Upper Extremity Data*
Pain Pain
Function Function
Emotional acceptance Emotional acceptance
Use of supports Hand positioning
Walking ability Manual dexterity
Gait Lifting ability
* Within each category, each of the six factors is graded 0 to 5. The higher the number,
the greater the improvement in outcome. The sum total for the six categories can
equal a Maximum Extremity Score of 30 points (5 × 6). Outcome is reported as a per-
centage of the Maximum Extremity Score.

28 Journal of the American Academy of Orthopaedic Surgeons


not converted to arthrodesis were
satisfied regarding pain, emotional
acceptance, and manual dexterity
and were dissatisfied regarding
function, positioning of the hand,
and lifting ability.
Osteoarticular or Bulk
Allografts
Indications and Advantages
Frozen allografts have been used
longer than any other tumor recon-
struction option. Allografts are
favored by some for their potential
for longevity because they function
as a biologic reconstruction. Incor-
poration of the allograft by the host
is a slow and incomplete process.
Osteoarticular allografts permit the
uninvolved portion of the joint to be
preserved; this approach allows the
strongest means of soft-tissue or
periarticular ligament reconstruc-
tion (Fig. 2). Although associated
with more early complications than
are endoprostheses, allograft recon-
structions stabilize after 3 to 5 years
and therefore do better in long-term
follow-up studies. Mankin et al19
found that, after 3 years, approxi-
mately 75% of grafts are retained by
patients and remain successful for
more than 20 years. Seventy per-
cent to 80% of patients obtain a
good or excellent functional result
after allograft reconstruction,
although this varies with type of
graft, anatomic site, and stage of
disease.19 The unpredictable early
outcomes with allografts and the
frequent need for multiple proce-
dures to obtain a successful end
result have led many orthopaedic
oncologists to favor modern endo-
prostheses. With their potential for
long-term stability, however, allo-
grafts play a key role in younger
patients (<20 years), in whom an
enduring reconstruction can limit
the additional revisions seen with
long-term follow-up of patients
with endoprosthetic constructs.
Vol 11, No 1, January/February 2003
Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD
Complications and external fixation, intravenous antibi-
Clinical Results otics, oral antibiotics for extended
Allografts used for tumor recon- periods, and reimplantation of a
struction have a high rate of early new allograft or conversion to a
complications. Cumulative compli- metallic endoprosthesis.
cation rates approach 50% in some In a retrospective review of 274
series, with most patients requiring allograft recipients after limb-spar-
additional surgery.19 Infection, frac- ing tumor resections with a mini-
ture, joint instability, and nonunion mum follow-up of 4 years, Berrey et
have vexed allograft reconstruction al21 reported a fracture incidence of
for 30 years.19-26 Immunologic com- 16% (43/274). There were no major
plications27 and risk of disease trans- distinguishing or predictive features
mission28 are of lesser concern but in the allograft group between
do exist. With osteoarticular allo- patients who had a fracture of the
grafts, osteoarthritis becomes mani-
fest at 5 to 10 years in 15% of pa-
tients and is best treated with a
resurfacing arthroplasty.19 Tumor
recurrence, infection, and fracture
are the most devastating complica-
tions and account for more than 85%
of allograft failures.19 Most of the
clinical outcome studies pertaining
to the use of massive allografts come
from the Orthopaedic Oncology
Unit at Massachusetts General
Hospital, with a series of more than
1,100 allograft reconstructions.19-24
Lord et al20 reported on the inci-
dence, nature, and treatment of
infections in bone allografts. A ret-
rospective review of 283 patients
with more than 2 years of follow-up
revealed an infection rate of 11.7%
(33/283). Gram-positive organisms,
particularly Staphylococcus epider-
midis, were the most common patho-
gens. Risk factors reflected those of
a population treated by wide resec-
tion of soft tissue and bone, chemo-
therapy, and radiation therapy.
Wound complications are the most A B
common problem and were associ- Figure 2 A 17-year-old boy presented
ated with early infection; additional with knee pain of 2 months’ duration.
surgical intervention is the most Radiographs, MRI, and biopsy confirmed
osteosarcoma. A, Initial postoperative
common risk factor for late infection. anteroposterior radiograph demonstrates
Eighty-two percent of infected cases distal femoral reconstruction with an
(27/33) were considered failures osteoarticular allograft stabilized with two
orthogonal dynamic compression plates.
and required amputation or removal The patient underwent a bone-graft proce-
of the allograft to control infection. dure 1 year later to treat an allograft-to-
Salvage is sometimes possible, but it host bone nonunion. B, Anteroposterior
radiograph 2 years after reconstruction
requires an aggressive approach demonstrates solid union of the osteosyn-
involving resection of the infected thesis site.
allograft, implantation of a spacer or
29
Malignant Bone Tumors: Limb Sparing Versus Amputation
allograft and those who did not.
There was a trend toward a higher
incidence of nonunion in patients
with fractures, but it was not statisti-
cally significant. The mean time to
fracture was 28.6 months after the
index surgery, with more than 70%
of fractures occurring within 3 years.
The results in this population after
treatment approached those of pa-
tients who had never had a fracture.
The mean time to union was 7.4
months (range, 4 to 14 months), with
all but four fractures treated with an
operation and most involving autog-
enous bone grafting. Weight bear-
ing was restricted until radiographic
union. The 43 patients underwent a
total of 59 operations. The authors
concluded that 9.3% of allograft
shaft fractures (4/43) may heal with
immobilization, but many require
treatment with internal fixation and
bone grafting. Several attempts may
be necessary, and sometimes ex-
change of the allograft or conversion
to a metallic endoprosthesis is neces-
sary.
Berrey et al21 classified the frac-
tures into three patterns. Type I
fractures (2/43) were seen soon after
surgery, with almost complete dis-
solution of the graft. These were
thought to be secondary to an im-
mune reaction to the allograft. Type
II fractures (22/43) were through the
shaft of the allograft, with a mean
time to fracture of 27.6 months.
Type III fractures (19/43) occurred
at the articular surface of osteoartic-
ular allografts at a mean of 31.6
months from surgery. These are
best treated with a standard resur-
facing total knee arthroplasty, when
feasible.
In a larger series of allograft re-
constructions,22 fractures occurred
at a rate of 17.7% (185/1,046). Mean
time to fracture was 3.2 years.
There were 8 Berrey type I fractures,
114 type II, and 63 type III. Sixty-
one fractures (33%) involved a screw
hole at the end of the plate. Neither
adjuvant chemotherapy nor radia-
30
tion influenced the rate of allograft
fracture.
Nonunion is another common
complication in the postoperative
course of allograft reconstructions.
All allografts have at least one os-
teosynthesis site that, until healed,
limits the amount of weight bearing
permitted through the reconstructed
limb. The location of the osteosyn-
thesis affects the healing potential.
Diaphyseal-to-diaphyseal osteosyn-
thesis sites have a higher risk of
delayed union or nonunion than do
metaphyseal-to-metaphyseal sites.
Supplemental autograft and stronger
internal fixation are recommended
at osteosynthesis sites in an effort to
decrease the rate of nonunion. In
the future, bone morphogenetic pro-
teins may play a similar role when
allograft reconstruction is per-
formed. Hornicek et al23 evaluated
factors affecting nonunion of the
allograft-host junction. Of 945 pa-
tients, 163 (17.3%) had a nonunion.
Those receiving chemotherapy had
twice the rate of nonunion. Two
hundred sixty-nine additional sur-
geries were performed on these 163
patients. In 114 patients, treatment
led to successful union. The per-
centage of failure increased as the
number of surgical procedures in-
creased. Despite treatment, 49 pa-
tients failed to demonstrate union of
the osteosynthesis site.
In comparing different types of
allografts, intercalary allografts have
better clinical outcomes than do
osteoarticular allografts, allograft-
prosthetic composites, and allografts
used for arthrodesis6,19,24 (Fig. 3).
Ortiz-Cruz et al24 reviewed 104 in-
tercalary allografts done over an 18-
year period (median follow-up, 5.6
years). Eighty-four percent (87/104)
were considered successful, with
retention of allograft and normal
extremity function. Infection, frac-
ture, stage of disease, and adjuvant
therapy all had adverse effects on
graft survival. Fifteen reconstruc-
tions failed, most within 3 to 4 years.
Journal of the American Academy of Orthopaedic Surgeons
Four were salvaged with a second
allograft, three by another recon-
struction technique; eight required
amputation (two for local recur-
rence). With two osteosynthesis
sites, nonunions might be expected
to be a common concern with inter-
calary allografts. Thirty-one of the
104 allografts (30%) failed to unite at
one or both junctions within 1 year,
but only seven remained ununited
(and were considered failures) after
additional surgical intervention.
Eighty-one additional surgical pro-
cedures were needed to achieve sat-
isfactory function in 92% of these
patients. Different modes of internal
fixation were used; plate fixation
spanning both osteosynthesis sites
was found to be superior to the use
of two shorter plates at either end of
the allograft.
Mankin et al19 found similar re-
sults in their review of 718 allograft
transplantations (mean follow-up,
78 months). Intercalary allografts
yielded the greatest satisfaction,
with excellent or good outcomes in
84% of cases. Osteoarticular allo-
grafts, allograft-prosthetic compos-
ites, and allograft arthrodeses had
excellent and good outcome rates of
73%, 77%, and 54%, respectively,
although they often required addi-
tional surgical procedures to achieve
these outcomes.
Regional Considerations
Most allograft reconstructions
are for the femur, and the results of
large studies primarily reflect the
outcome for this region. Hornicek
et al25 reviewed the largest series to
date of proximal tibial osteoarticular
allografts, consisting of 38 recon-
structions (38 patients) in 15 years.
Fifty-five percent of the patients
experienced one or more complica-
tions, which were managed with
multiple subsequent procedures.
Three amputations were done for
deep infections. About one third of
the patients required removal of the
original allograft and reconstruction
 Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD

A B C D

Figure 3 A 21-year-old man presented with thigh pain. Anteroposterior (A) and lateral (B) radiographs of the femur show a permeative
diaphyseal lesion with cortical erosion (white arrows). C, Coronal T2-weighted MRI scan demonstrates the diaphyseal lesion (black
arrow). Open biopsy confirmed Ewing’s sarcoma. D, Postoperative anteroposterior radiograph of the femur after wide tumor resection
and intercalary allograft reconstruction stabilized with a statically locked intramedullary nail.

with a new allograft or conversion
to metallic prosthesis. Ultimately,
66% had a good or excellent func-
tional result. The study also com-
pared outcomes and complications
between the subset of patients treat-
ed with chemotherapy, radiation
therapy, or both to those without
adjuvant therapy. The only signifi-
cant (P < 0.05) difference observed
between the groups was the higher
incidence of fracture in the patients
treated with chemotherapy.
Proximal humeral osteoarticular
allografts are an attractive option be-
cause of their potential for soft-tissue
reconstruction, healing, and func-
tion. O’Connor et al18 reported on
eight patients treated with this tech-
nique, a subset of 57 patients who
underwent limb-sparing tumor re-
sections and various forms of recon-
struction. There was no nonunion
or cases of instability, but half of the
patients experienced subchondral
fractures and collapse of the articu-
lar surface. Three of these four pa-
tients were asymptomatic; the other
was treated with conversion to a
prosthesis. Functional rating aver-
aged 71% by the MSTS system, with
patients least satisfied with function
and positioning of the hand. Com-
pared with endoprosthetic recon-
struction, osteoarticular allografts
resulted in superior function after
intra-articular resection of the proxi-
mal humerus. Shoulder arthrodesis
using an intercalary allograft com-
bined with plate fixation and vascu-
larized fibular grafting is an excel-
lent method of reconstruction after
extra-articular resection of the proxi-
mal humerus.
Getty and Peabody 26 reported
similar results in 16 patients who
underwent osteoarticular allograft
reconstruction after intra-articular
resection of the proximal humerus.
At a mean follow-up of 47 months,
the mean MSTS functional evalua-
tion score was 70%. Deterioration
was noted to continue with time
from surgery. The authors have
stopped doing the procedure
because of the unacceptable rates
of epiphyseal fragmentation (4/16),
instability (11/16), fracture (4/16),
and infection (1/16).
Allograft-Prosthetic Composites
Clearly there are benefits and
inherent drawbacks to either allo-
graft or endoprosthetic reconstruc-
tion. By combining the two meth-
ods or using an allograft-prosthetic
composite, the surgeon can tailor
the procedure to help diminish the
inherent risks encountered when
either reconstruction is used alone.
The composite helps restore as
much bone stock as possible and
offers joint stability that is often
difficult to obtain with osteoarticu-
lar allograft reconstruction. By

Vol 11, No 1, January/February 2003 31

Malignant Bone Tumors: Limb Sparing Versus Amputation

resurfacing the allograft bone with

an implant, cartilage degradation
is no longer a potential problem 5
to 10 years after reconstruction
(Fig. 4).
Gitelis and Piasecki14 performed
11 hip and 10 knee reconstructions
and 1 elbow reconstruction in 22 pa-
tients (mean follow-up, 45 months).
Mean MSTS functional score was
94.3%. Five patients had a non-
union, four of which healed after
bone grafting; one was converted to
a megaprosthesis. There were no
dislocations. Graft resorption did
not occur in this small number of pa-
tients, and no revisions were done A B C
for implant loosening.
Figure 4 A 14-year-old boy presented with knee pain of 3 months’ duration and an
enlarging mass. A, Anteroposterior radiograph of the knee demonstrates an eccentric lytic
proximal tibial metaphyseal lesion with cortical destruction and soft-tissue extension
Techniques With Special (arrow). Biopsy confirmed osteosarcoma. Anteroposterior (B) and lateral (C) radiographs
Indications demonstrate skeletal reconstruction with a rotating-hinge knee prosthesis and proximal
tibial allograft-prosthetic composite stabilized with a dynamic compression plate.

Vascularized Bone Grafts

Vascularized bone grafts can be
taken from the iliac crest, rib, scapula,
or fibula. Of these options, only vas-
cularized fibular grafts are suited for
the large skeletal defects left after
wide resection of a malignant bone
tumor. Compared with allografts,
vascularized autografts offer a more
rapid incorporation, stronger initial
construct secondary to graft hyper-
trophy, and absence of immunologic
problems. Vascular grafts change
not the pattern of bony repair but
rather the rate of repair. Final matu-
ration and hypertrophy of grafts
is consistent with Wolff’s law. 29
External fixation is preferable to
plate fixation because it maximizes
these stresses and allows for greater
hypertrophy and ultimate strength
of the graft. Ideally suited for chil-
dren and young adults, this method
of biologic reconstruction has the
potential to be enduring without
need for revision surgery later in life.
Vascularized autografts also are used
with the poorly vascularized tumor
bed commonly found in previously
irradiated tissue and when a delay in
osteosynthesis healing is anticipated
secondary to adjuvant therapy with
radiation, chemotherapy, or both.
The main disadvantages of vascular-
ized autograft are the increased
surgery time, surgical site morbidity,
and size limitations.
Few published reports focus on
vascularized autograft in tumor
reconstruction, and long-term out-
come data are lacking.30 Hsu et al31
reviewed a consecutive series of 30
patients who underwent skeletal
reconstruction by vascularized fibu-
lar transfer after resection of primary
bone tumors. Mean follow-up was
36 months (range, 24 to 85 months),
with union achieved in 90% (27/30)
at an average of 7.6 months. The
mean fibular graft length was 18.9
cm (range, 10 to 30 cm). Functional
results were evaluated in 24 patients,
with 9 excellent, 7 good, 6 fair, and 2
poor results. When used for inter-
calary grafts (14 patients), the func-
tional results were better than those
seen with arthrodesis procedures (10
patients). There was a high compli-
cation rate (50%), but many were
managed nonsurgically and resolved
without greatly affecting the final
outcome. Complications included
three nonunions, three deep infec-
tions, three stress fractures, two local
recurrences, and an assortment of
soft-tissue complications.
Arthrodesis
Arthrodesis creates a stable,
painless, durable limb. Indications
for arthrodesis are extra-articular
joint resection or extensive muscle
resection with lack of remaining
muscle to power the joint, or when
the desire for joint stability is para-
mount. The two most common re-
gions for this technique are the knee
and shoulder.
Knee arthrodesis can be accom-
plished with allografts, nonvascu-
larized autografts, vascularized
rotational fibular grafts, external fix-
ation with bone transport, or some
combination of these techniques.
Fixation is achieved with either
compression plating or intramedul-
lary nailing. Intramedullary fixa-
tion is favored for arthrodesis be-
cause of a decreased rate of graft

32 Journal of the American Academy of Orthopaedic Surgeons


fracture and nonunions. The knee is
aligned in 10° to 15° of flexion and
0° to 5° of valgus. In the skeletally
mature individual, the limb is short-
ened 1 to 2 cm to allow for foot
clearance during the gait cycle. In
skeletally immature patients, the
limb may be lengthened with the
grafting technique; the expectation
is that the contralateral normal limb
will continue to grow, with the
result that limb length at skeletal
maturity on the operated side will
be equal or slightly shorter. The
procedure is associated with a high
rate of complications (approximate-
ly 50%), including all of the inherent
risks of allograft reconstruction.
Despite this complication rate, how-
ever, most patients achieve success-
ful union and have a durable, func-
tional limb.32-34
The shoulder joint is challenging
to reconstruct, given the extreme
range of motion and lack of inherent
static stability. The few published
reports that discuss shoulder
arthrodesis in tumor reconstruction
have small numbers of patients (5 to
10). Notable rates of infection, frac-
ture, and nonunion exist, as with
knee arthrodesis.32 Most patients
obtain stable fusion, allowing satis-
factory function of the upper ex-
tremity.18,32
Wolf et al33 reviewed the long-
term results in 73 patients who,
from 1967 to 1985, underwent resec-
tion arthrodesis of the knee with
autogenous grafts. Forty patients
followed for more than 10 years
formed the basis of the evaluation.
Intramedullary rods were used to
stabilize hemicortical femoral or tib-
ial allografts and nonvascularized
autogenous fibular grafts to the
native femur and tibia. A high inci-
dence of complications (52%) was
evident, yet most patients eventual-
ly achieved a successful outcome
with preservation of the limb, and
86% were independent ambulators
at long-term follow-up. The most
common complications were graft
Vol 11, No 1, January/February 2003
Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD
fatigue fracture (51%), delayed
union (23%), rod migration or rod
fracture (25%), peroneal nerve palsy
(8%), and infection and wound
problems (23%). Thirty-seven of the
40 patients (93%) achieved a solid
reconstruction. Two patients
required an above-knee amputation,
one for infection and the other for
local tumor recurrence. One addi-
tional patient sustained a commi-
nuted traumatic fracture of the
fusion and was treated with an
allograft arthrodesis. The recon-
structions proved to be durable,
and patient satisfaction and func-
tion remained high for decades,
with an average MSTS functional
score of 77%.
Weiner et al34 evaluated 39 pa-
tients treated with resection arthrod-
esis done with an intercalary allo-
graft fixed with an intramedullary
nail. In 31 patients, this procedure
was the index reconstruction; in
eight, it was done after failure of a
different type of tumor reconstruc-
tion. Proximal and distal osteosyn-
thesis sites both healed, and function
was satisfactory in 32 patients.
Nonunion occurred in seven pa-
tients (one junction in six patients,
both junctions in one). The non-
union was healed in five of the
seven treated with bone grafting,
repeat internal fixation, or exchange
allografting; two patients went on to
above-knee amputation. An addi-
tional patient from the study under-
went above-knee amputation for
local recurrence. Fatigue fracture of
the allograft occurred in five pa-
tients, all within metaphyseal bone.
Overall, the rate of complication
was lower than that experienced
with autograft arthrodesis.
Expandable Prostheses
Expandable prostheses were
developed in an attempt to over-
come anticipated limb-length dis-
crepancies in the growing child
treated with limb-sparing surgery.
The first approach includes the
Lewis Expandable Adjustable
Prosthesis (LEAP).35 Expansion of
the LEAP is achieved by a modified
Jacob’s chuck mechanism. Rotation
of the outer sleeve of the prosthesis
engages the threads on the inner
shaft, thereby increasing the length
of the prosthetic shaft with each rev-
olution. An average lengthening is
1.5 to 2 cm; the average overall
extension capability of a LEAP is 6
to 9 cm. Collapse of the expansion
mechanism, observed early in its
use, has been addressed with the use
of spacer rings. Problems with tita-
nium debris and fatigue failure of
expandable prostheses led to the
alternative use of modular systems.
These systems use a Morse taper
locking system to connect segmental
parts. Exchange of intercalary seg-
ments can be performed as the
patient grows, adding 2 cm to the
length of the segment replaced.
When extremity length discrep-
ancy reaches approximately 2 cm or
more, an expansion procedure is in-
dicated. The original incision is used,
and the pseudocapsule around the
prosthesis is excised to prevent
problems with joint stiffness after
lengthening and to relieve tension on
the neurovascular bundle. Eckardt
et al36 reported on their 14-year ex-
perience with 32 expandable pros-
theses. Nineteen of the 32 patients
(59%) survived, with a median fol-
low-up of 105 months. Sixteen of
the patients (50%) did not undergo
an expansion because of death, am-
putation, or short duration of follow-
up. The remaining 16 patients un-
derwent 32 expansion procedures,
to a maximum of 9 cm, without
infection. The average time from
implantation to the first lengthening
was 19 months. Most of the length-
enings were 1.5 to 2 cm. More than
50% of the patients had at least
one complication, most frequently
aseptic loosening or failure of the
prosthesis, collapse of the LEAP, tem-
porary nerve palsy, or flexion con-
tractures. The average MSTS ratings
33
Malignant Bone Tumors: Limb Sparing Versus Amputation
were good to excellent at the knee,
fair to good at the hip, and fair about
the shoulder. The authors concluded
that, in children and the skeletally
immature, rehabilitation can be
problematic; early loss of joint mo-
tion and fixed flexion contractures
can occur. With advances in tech-
nology, a noninvasive prosthetic
lenghtening mechanism is now
being evaluated clinically.
Rotationplasty
Rotationplasty, another recon-
struction option in the skeletally im-
mature patient, can be done after
wide resection about the knee when
the sciatic nerve can be preserved.
The tibia is rotated 180° and fused
to the femur, with the ankle joint
placed at the level of the contralateral
knee. The procedure creates a func-
tional below-knee amputation; out-
come far exceeds that associated
with above-knee ablation. The main
indication for this technique is in a
very young child with an extensive
malignant bone tumor and several
years of growth remaining. Rotation-
plasty also may be used in adults
when soft-tissue coverage is inade-
quate after extensive tumor resec-
tion. In general, the procedure is
associated with a low incidence of
complications and a highly func-
tional and durable extremity recon-
struction.37 Advantages include the
maintenance of growth and a func-
tioning “knee” joint, the ability to
tailor the procedure to obtain limb-
length equality at skeletal maturity
without further operations, an energy-
efficient gait pattern, and avoidance
of the problems of neuromas and
stump breakdown seen with ampu-
tations. With the advent of expand-
able prostheses in the late 1980s,
however, the indications for rota-
tionplasty have narrowed. A full
presurgical discussion is essential so
that the patient and family under-
stand the advantages and cosmetic
appearance of the reconstructed
limb, thus limiting postoperative
34
dissatisfaction or psychological
problems. Meetings with other pa-
tients who have had the procedure
are beneficial.
Kotz37 reviewed the results of 40
patients treated with rotationplasty
between 1976 and 1988. Thirty were
followed for more than 3 years. No
patient developed local recurrence;
six died from metastatic disease, and
the remaining 24 were tumor free.
All patients were prosthetic ambula-
tors without additional supports,
and most participated in sports.
Functional evaluation revealed 68%
excellent, 28.5% good, 3.5% fair, and
no poor results according to the
system of Enneking et al.38 Compli-
cations of rotationplasty include
postoperative vascular occlusion,
pseudarthrosis between femur and
tibia, nerve palsies, rotational mal-
alignment, and diffuse osteopenia in
the distal limb bones. The high level
of function achieved by most pa-
tients far outweighs the appearance
of the limb, limiting the psychologi-
cal problems associated with rota-
tionplasty.37,39 Long-term follow-up
studies have shown the high durabil-
ity of rotationplasty, with continued
excellent or good results at 8 years.39
Limb Lengthening
The Ilizarov bone transport pro-
cedure and other techniques of limb
lengthening can be used to regain
bone length after resection and re-
construction. Limb lengthening by
distraction osteogenesis or bony
transport has limited utility after
resection of malignant bone tumors
when used as the primary recon-
struction technique. The large os-
seous defect is difficult to replace
and requires extended periods of
treatment, which are associated
with significant complications. Fre-
quently, the final functional result
with this technique is poor.40 Limb-
lengthening procedures are better
suited as adjuncts to other methods
of reconstruction or for smaller
defects.
Journal of the American Academy of Orthopaedic Surgeons
Limb-Sparing Procedures
Compared With
Amputation
Survival and Local
Recurrence Rates
In comparing limb-sparing proce-
dures with amputation, the points
selected as outcome measures are
important. The primary goal of any
oncologic procedure is local tumor
control to diminish local recurrence
and improve overall survival.
Limb-preserving procedures have
not decreased overall survival
rates4,5,11,19,41,42 (Table 3). Local recur-
rence associated with limb-sparing
resection and reconstruction is
slightly greater than it is after ampu-
tation or joint disarticulation, but
this has not been found ultimately to
affect patient survival. 4,41 In the
largest series to date comparing
limb-sparing surgery with amputa-
tion in 227 patients with osteosarco-
ma of the distal femur, Rougraff et
al41 found local recurrence in 8 of 73
patients treated with limb preserva-
tion, in 9 of 115 patients treated with
above-knee amputation, and in none
of 39 patients treated with hip disar-
ticulation.
Functional Outcome
The MSTS system for assessing
the function of reconstructive pro-
cedures (Table 2) is designed to
allow for comparison of results.16
Functional outcome studies com-
paring limb preservation and
amputation have inherent limi-
tations, however, including the
inability to randomize treatment
and the subjective nature of impor-
tant outcome measures. Most func-
tional outcome measures favor
nonarthrodesis procedures because
range of motion is measured. Most
of the studies designed to assess
functional outcome focus on pa-
tients with perigeniculate tumor
resections. Good and bad out-
comes occur with whatever proce-
dure is used, and there is little dif-
 Matthew R. DiCaprio, MD, and Gary E. Friedlaender, MD
Table 3
Limb Sparing Versus Amputation for Extremity Bone Sarcomas
Management
Outcome Measure Limb Sparing* Amputation†
Local recurrence4,5,11,19,41,42 5% to 10% 5%
Survival4,5,11,19,41,42 70% 70%
Functional outcome41,42,44-47 Good Good
Initial cost43 High Low
Long-term cost43 Less than amputation More than limb-
sparing procedure
* 85% to 90% of patients with extremity bone sarcomas can be managed with
limb-sparing surgery.
† Only 10% to 15% of patients require ablative surgery as initial management.
ference in quality-of-life outcomes and were the most protective of the
between limb-sparing and amputa- limb.
tive surgeries.43 Kawai et al46 evaluated clinical
Rougraff et al41 found that their outcomes, length of resection, and
limb-preservation group had higher energy cost of walking after pros-
functional scores than did the group thetic knee replacement for malig-
treated with amputation but that nant tumors of the distal femur. The
the limb-preservation patients fre- mean free-walking velocity was 79%
quently required additional surgical of normal, reflecting a decrease in
procedures to reach peak function. both cadence and stride length.
Renard et al42 found functional re- Also, mean energy cost during walk-
sults to be significantly (P = 0.0001) ing was 35% greater than that of
better after limb-saving surgery normal control subjects and correlat-
compared with ablative therapy; ed with the percentage of femur that
however, complications were three had been resected. Hillmann et al47
times more common in the limb- reported on 67 patients with malig-
saving cohort. nant tumors of the distal femur or
Otis et al 44 studied the energy proximal tibia who were treated by
cost during gait by measuring oxy- rotationplasty or endoprosthetic
gen consumption in 14 patients with reconstruction. Patients with a rota-
custom-made knee prostheses and tionplasty had a mean MSTS func-
12 patients who had had above- tional score of 80% (24/30) com-
knee amputations and been fitted pared with 83.3% (25/30) for patients
with an artificial limb. They con- treated with an endoprosthesis.
cluded that prosthetic reconstruc- Those with a rotationplasty had
tion provides superior function fewer restrictions in their daily activ-
because these patients had a lower ities and required ambulatory assis-
energy cost during gait. In contrast, tive devices less frequently than did
the patients studied by Harris et al45 those reconstructed with a prosthe-
functioned similarly and walked sis. Finally, McClenaghan et al48
with comparable velocity, efficien- compared oxygen consumption in
cy, and rate of oxygen consumption patients treated with above-knee
whether they had had an amputa- amputation, arthrodesis, or rota-
tion, arthrodesis, or arthroplasty. tionplasty. Patients treated by ro-
The patients treated with endopros- tationplasty walked the most effi-
theses lived more sedentary lives ciently.
Vol 11, No 1, January/February 2003
Psychological Factors
Whether limb-sparing surgery
offers a psychological outcome ad-
vantage compared with amputation
for extremity sarcomas has yet to be
demonstrated because no long-term
prospective or comparative studies
have been done.5,49 In a small, retro-
spective, one-time psychological
assessment of patients treated for
lower extremity sarcomas, no differ-
ences between amputation and limb
sparing were found regarding cog-
nitive capacity, mood, body image,
global physical functioning, global
adjustment to illness and surgery,
and lifetime prevalence of psycho-
logical disorders before or after
surgery.49 Most patients adjust well
to both the disease and the required
surgical treatment if they have no
premorbid psychological disorders.5
Costs
Grimer et al43 demonstrated that
endoprosthetic reconstruction is less
expensive than amputation, based
on a 1997 cost analysis and 20-year
follow-up. Their formula takes into
account the projected need for revi-
sion surgery, based on rates of asep-
tic loosening of 2.5% per year and
on rates of other causes of early fail-
ure (eg, infection, implant failure) of
1.5% per year.
Future Directions
As experience is gained, the abili-
ty to amend methods of treatment
to improve outcomes will increase.
Endoprostheses continue to be
improved. Long-term results of
modular rotating-hinge knee com-
ponents are anticipated to yield
better results than those of simple-
hinge knee prostheses. A few insti-
tutions have had experience with an
endoprosthesis that is lengthened
noninvasively by the application of
external electromagnetic force, and
development continues. Soft-tissue
reattachment and ligament recon-
struction are easier to perform be-
cause of the use of osteoarticular
35
Malignant Bone Tumors: Limb Sparing Versus Amputation
allografts. With the development of
tendon-attachment devices or en-
hanced tendon-anchorage devices
for prostheses, the indications and
outcomes for proximal tibial pros-
theses are likely to broaden and im-
prove.3 Better stability around the
hip and shoulder after prosthetic
reconstructions fit with these special
devices should improve functional
results in these regions. Extracor-
tical bone-bridging fixation will
likely improve the longevity of
prostheses by walling off the pros-
thesis-bone interface and adding
additional points of fixation to
improve construct strength.3,9
For reconstructions using allo-
grafts, bone morphogenetic proteins
may decrease nonunion rates. A
better understanding of allograft
biology, as well as either closer
matching of allografts to recipients
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25. Hornicek FJ Jr, Mnaymneh W, Lackman
RD, Exner GU, Malinin TI: Limb sal-
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29. Shaffer JW, Field GA, Goldberg VM,
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30. Brown KL: Limb reconstruction with
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64-73.
31. Hsu RW-W, Wood MB, Sim FH, Chao
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34. Weiner SD, Scarborough M, Vander
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sparing surgery in skeletally immature
patients with osteosarcoma: The use of
an expandable prosthesis. Clin Orthop
1991;270:223-230.
36. Eckardt JJ, Kabo JM, Kelley CM, et al:
Expandable endoprosthesis reconstruc-
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about the knee. J Bone Joint Surg Am
1990;72:1477-1485.
46. Kawai A, Backus SI, Otis JC, Healey JH:
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47. Hillmann A, Hoffmann C, Gosheger G,
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48. McClenaghan BA, Krajbich JI, Pirone
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37
 Use of Antibiotic-Impregnated Cement
in Total Joint Arthroplasty

Thomas N. Joseph, MD, Andrew L. Chen, MD, and Paul E. Di Cesare, MD

Abstract

The use of antibiotic-impregnated cement in revision of total hip arthroplasty pro- (beads of Palacos R with genta-
cedures is widespread, and a substantial body of evidence demonstrates its effi- micin) are not currently available in
cacy in infection prevention and treatment. However, it is not clear that the United States. Some hospital
it is necessary or desirable as a routine means of prophylaxis in primary total pharmacies (2.2%) prepackage ce-
joint arthroplasty. In the management of infected implant sites, antibiotic- ment with antibiotic for later use in
impregnated cement used in one-stage exchange arthroplasties has lowered rein- the operating room.3
fection rates. In two-stage procedures, use of beads and either articulating or A survey of 1,015 orthopaedic
nonarticulating antibiotic-impregnated cement spacers also has lowered reinfec- surgeons in the continental United
tion rates. In addition, spacers reduce “dead space,” help stabilize the limb, and States revealed that 56% have im-
facilitate reimplantation. Problems associated with antibiotic-impregnated pregnated their bone cement with
cement in total joint arthroplasty include weakening of the cement and the genera- antibiotic for at least some cases.2
tion of antibiotic-resistant bacteria in infected implant sites. Surgeons specializing in joint recon-
J Am Acad Orthop Surg 2003;11:38-47 struction were more likely to use
antibiotic in bone cement (88%).
Sixty-five percent of all surgeons
surveyed reported that they adjust-
In 1970, Buchholz and Engelbrecht1 laminar airflow (present in 49% of ed antibiotic usage according to
introduced the concept of impreg- hospital operating rooms), body microbial sensitivity; of this group,
nating acrylic bone cement with exhaust suits (in 69%), high airflow 70% used tobramycin; 26%, genta-
antibiotic as a possible means of (in 85%), and ultraviolet lights (in micin; 18%, vancomycin; 15%,
preventing infection in patients 14%).2 Reported infection rates after cephalosporins; and 3%, combined
undergoing total joint arthroplasty. revision total joint arthroplasty vary antibiotics. Antibiotics in liquid
Since then, antibiotic-impregnated widely because of the large number
cement has become more commonly of patient variables.
used for revision total joint arthro- Several types of acrylic bone
plasty and, as antibiotic-impregnated cement in current use incorporate Dr. Joseph is resident, Department of Ortho-
cement spacers or beads, for treat- antibiotics, either premixed by the paedic Surgery, Musculoskeletal Research
ment of infection during two-stage manufacturer or added by the sur- Center, NYU–Hospital for Joint Diseases, New
revision arthroplasty than it has for geon in the operating room. In the York, NY. Dr. Chen is resident, Department of
United States, commonly used Orthopaedic Surgery, Musculoskeletal Research
infection prophylaxis in primary
Center, NYU–Hospital for Joint Diseases, New
total joint arthroplasty. Even with- cements such as Palacos (Smith & York. Dr. Di Cesare is Associate Professor of
out the contribution of antibiotic- Nephew, Memphis, TN), Simplex Orthopaedic Surgery, Department of Ortho-
impregnated cement, the infection (Howmedica, Rutherford, NJ), paedic Surgery, Musculoskeletal Research
rate after standard primary total CMW (DePuy, Warsaw, IN), and Center, NYU–Hospital for Joint Diseases, New
Zimmer (Zimmer, Warsaw, IN) are York.
joint arthroplasty in modern oper-
ating rooms has been reduced to mixed with antibiotics by the sur-
Reprint requests: Dr. Di Cesare, 15th Floor,
between 0.3% and 2%. A survey geon. Commercially prepared ad- 301 East 17th Street, New York, NY 10003.
from 1995 concerning orthopaedic mixtures such as AKZ (Simplex P
operating room practices and equip- with colistin and erythromycin), Copyright 2003 by the American Academy of
ment suggested that this reduction Refobacin-Palacos R (Palacos R with Orthopaedic Surgeons.
has been achieved by the access to gentamicin cement), and Septopal

38 Journal of the American Academy of Orthopaedic Surgeons


form, generally considered to be
less desirable than the powdered
form (because of the effects to
cement polymerization), were used
by as many as 11% of the surgeons
surveyed, possibly because of the
general unavailability of a pow-
dered form of gentamicin in the
United States. In performing prima-
ry arthroplasties, approximately
12% of surgeons always used anti-
biotic-impregnated cement, 69%
never used it, and 19% used it some-
times. Of those who did use it, 68%
did so in less than one third of their
aseptic revision total joint arthro-
plasties. However, over 80% used it
more than two thirds of the time in
septic revision total joint arthroplas-
ty. Over half often used antibiotic-
impregnated cement beads in two-
stage reimplantation for infections;
32% often used antibiotic-impreg-
nated cement spacers in hips; and
69% often used such spacers in
knees. Of those using antibiotic-
impregnated cement, 28% used a
single-stage reimplantation in total
joint arthroplasty infection, while
72% used a two-stage approach.2
These data suggest that no com-
monly accepted standard exists
regarding the use of antibiotic-
impregnated cement in orthopaedic
surgery.
The FDA takes no official posi-
tion on the use of antibiotics in
cement. A document issued July 17,
2002, requires that cement labeling
contain the warning, “PMMA bone
cement is contraindicated in the
presence of active or incompletely
treated infection, at the site where
the bone cement is to be applied.”4
Laboratory Studies
A number of criteria must be met
for antibiotics to be effective when
mixed with methylmethacrylate.
The preparation must be sufficiently
thermally stable to withstand the
heat of polymerization. The antibi-
Vol 11, No 1, January/February 2003
otic must not be adversely affected
by body temperature and must be
water soluble so that it can diffuse
into surrounding tissues. The
antibiotic must have a bactericidal
effect at the tissue levels attained;
furthermore, it must be released
gradually over an appropriate time
period. The preparation must
evoke minimal local inflammatory
or allergic reaction. Development of
resistance should be rare to nonexis-
tent; common pathogens must be
considered, including Staphylococcus
aureus, S epidermidis, coliform, and
others, such as anaerobes. Finally,
the antibiotic must not significantly
compromise mechanical integrity,
especially if the cement is used for
implant fixation.
In vitro analyses of antibiotic elu-
tion and mechanical stability have
been done with a variety of antibiot-
ic-cement combinations. The stable
incorporation of aminoglycoside
antibiotics (eg, gentamicin and
tobramycin) into cement and their
elution therefrom are well estab-
lished. Vancomycin is gaining pop-
ularity because of its effectiveness
against methicillin-resistant bacteria
as well as its general availability.
Although penicillins and cephalo-
sporins exhibit adequate elution and
stability, they are often avoided be-
cause of their potential allergenicity.
In one study, in vitro testing of van-
comycin- and tobramycin-impreg-
nated cement demonstrated elution
of antibiotic for the entire 9-week
study period; the highest elution
rate occurred at 18 hours (between 3
and 5 times the rate that occurred at
72 hours).5 Ciprofloxacin, a more re-
cent addition to bone cement, may
gain in popularity because of its
wide antibiotic spectrum and gener-
al availability. Ciprofloxacin elution
met or exceeded the minimum
inhibitory concentration for com-
mon organisms associated with
osteomyelitis for up to 42 days. 6
Recent studies 7,8 indicate that
ciprofloxacin may inhibit bone, liga-
Thomas N. Joseph, MD, et al
ment, and soft-tissue healing; this is
a concern, particularly in total knee
revision surgery.
Lipids may impede the leaching
process from cement. The peptide
antibiotics vancomycin and poly-
myxin B nonapeptide have been
shown to elute for a longer period
than do the nonpeptide antibiotics
gentamicin, novobiocin, and eryth-
romycin.9 Molecular weight also
appears to play a role. One in vitro
study indicated that vancomycin is
eluted 10 times less efficiently than
tobramycin from antibiotic-impreg-
nated cement, probably because of
its higher molecular weight.10 Other
in vitro studies, however, found no
marked difference between the two.11
Palacos cement appears to pro-
vide the best elution profile for most
antibiotics. A study of the elution
characteristics of Palacos and CMW
acrylic cements showed that CMW 1
released 24% less tobramycin and
36% less vancomycin than did Pala-
cos; CMW 3 released 34% less tobra-
mycin and 38% less vancomycin.5
Another in vitro study, in which
Palacos and Simplex beads and
spacers were impregnated with 4 g
of either vancomycin or tobramycin
in 40 g of cement, also showed
antibiotic eluting from Palacos at
higher levels.12 Concentrations re-
mained above the minimum inhibi-
tory concentration for S aureus
longer in Palacos than in Simplex.
In another study, elution of van-
comycin, daptomycin, and amikacin
from Palacos exceeded that of
Simplex, Zimmer Dough-Type, and
Zimmer LVC.13
Commercially prepared antibiot-
ic cement may be superior to intra-
operatively mixed cement. Elution
of gentamicin and tobramycin from
laboratory-customized Zimmer,
Simplex, or Palacos beads compared
with elution from commercially pre-
pared gentamicin-PMMA (Septopal)
beads showed that more total an-
tibiotic was eluted from the latter,
and was maintained at higher con-
39
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
centrations, than it was in the beads
to which antibiotics were added by
the investigators.14
The results of studies of the effect
on elution of combinations of antibi-
otics, typically vancomycin and
tobramycin, are inconclusive. In one
study, elution of vancomycin was
minimally affected by tobramycin,
while elution of tobramycin was
reduced by vancomycin.10 In anoth-
er study, the elution rate of tobramy-
cin increased by 68% and that of van-
comycin by 103% when these antibi-
otics were combined.15 In the first
study,10 vacuum-mixed Simplex was
used, and in the second,15 nonvacu-
um-mixed Palacos. In both, the most
advanced means of measuring an-
tibiotic were used. An in vivo study
using the prosthesis of antibiotic-
loaded acrylic cement (PROSTA-
LAC; Smith & Nephew, Memphis,
TN) demonstrated a statistically sig-
nificant (P = 0.011) increase in the
elution of vancomycin when the
dose of tobramycin was increased
from 2.4 to 3.6 g per dose of cement;
Simplex was used in 12 patients and
Palacos in 37.16 The investigators
changed the cement early in their
study after finding evidence in the
literature suggesting better antibiotic
elution from Palacos.
Klekamp et al10 demonstrated that
compressive and fatigue strength
decreased with the addition of van-
comycin or tobramycin to cement.
Cement impregnated with 1, 2, or 3
g of vancomycin failed at 90%, 70%,
and 50%, respectively, of the num-
ber of cycles to failure for antibiotic-
free cement. Likewise, cement with
1.2 and 2.4 g of tobramycin failed at
80% and 60%, respectively, of the
number of cycles to failure for con-
trols. Although fatigue strength
data were statistically significant (P
< 0.05), the results of compressive
strength tests demonstrated a de-
creasing trend yet were not statisti-
cally significant. Routinely used
lyophilized vancomycin was found
to greatly reduce cement fatigue
40
strength. The authors suggested
using vancomycin P (an ultrafine
powder) in bone cement intended
for prosthesis fixation because it has
less detrimental effect on cement
strength. Askew et al17 found that
the addition of 1 g of either tobra-
mycin or vancomycin resulted in
nominal bending strength reduc-
tions (6% and 1%, respectively,
compared with controls). Another
study confirmed that the addition of
1.2 g of tobramycin to 40 g of Sim-
plex powder did not significantly de-
crease fatigue strength.18 Vancomy-
cin L (lyophilized) should be finely
ground when used for prosthesis
fixation to prevent mechanical
weakening; however, large crystals
should not be completely pulver-
ized when preparing beads or spac-
ers because the crystals facilitate
antibiotic elution.
Morita and Aritomi19 showed no
reduction in tension and bending
strengths of cefuzonam-impregnated
cement when <3 g was used. Earlier
studies showed similar results with
respect to compressive and tension
strengths of cement impregnated
with gentamicin, oxacillin, and cefa-
zolin.20 Addition of more than 4.5 g
of gentamicin has been shown to
Table 1
Reported Doses* of Antibiotics Used in Antibiotic-Impregnated
Cement13,26,44,53-55
Antibiotic Dose for Prosthesis Fixation
Amikacin 1g
Cefazolin NR
Cefotaxime 3g
Cefuroxime 1.5 to 3 g
Clindamycin NR
Erythromycin 0.5 to 1 g
Gentamicin 1g
Ticarcillin Not appropriate
Tobramycin 1.2 g
Vancomycin 1 g (vancomycin P)
*Per 40-g batch of cement
P = ultrafine powder, L = lyophilized, NR = not reported in the literature
Journal of the American Academy of Orthopaedic Surgeons
substantially weaken cement to a
level below that appropriate for
implant fixation.21 Reduction of no
more than 10% in bone cement
strength is considered acceptable for
use in total joint arthroplasty fixa-
tion; however, weaker antibiotic-
impregnated cement may be used in
beads and spacers. Table 1 lists ap-
propriate doses of antibiotic im-
pregnation in cement for prosthesis
fixation and for spacers and beads.
Vacuum mixing, which reduces
the number of voids in bone ce-
ment, improves the mechanical
properties of antibiotic-impregnated
cement. When cylindrical cement-
vancomycin specimens were sub-
jected to fatigue testing (uniaxial
mode), cycles to failure were 15% to
58% greater in vacuum-mixed speci-
mens than in those mixed at atmos-
pheric pressure. Fracture of antibi-
otic-impregnated cement specimens
during cyclic testing was reduced
up to tenfold with vacuum mixing
or with vigorous pulverizing of the
antibiotic before mixing.10 Another
study showed vacuum mixing also
reduced fivefold the radiograph-
ically apparent porosity of antibiotic-
impregnated cement specimens but
may inhibit antibiotic release.17 In
Dose for Spacers and Beads
2g
4 to 8 g
NR
NR
4 to 8 g
NR
2 to 5 g
5 to 13 g
2.4 to 9.6 g
3 to 9 g (vancomycin P or L)
 Thomas N. Joseph, MD, et al

one study, vancomycin vacuum-
mixed with Simplex (1:40 ratio)
released slightly less than half the
antibiotic that air-mixed cement did;
no antibiotic release was detectable
after 48 hours. 13 Another study,
however, found adequate antibacte-
rial activity lasting for 21 days.17
Dextran has been used to en-
hance porosity and thus improve the
elution of antibiotic. One prepara-
tion with dextran released approxi-
mately 4 times as much antibiotic as
did a dextran-free preparation, and
elution remained detectable for 10
days versus 7 days, respectively.13
However, dextran degrades the
mechanical properties of cement;
therefore, its use for prosthetic fixa-
tion should be extremely limited.
Centrifugation, another preparation
technique, markedly increased the
fatigue life of Simplex both with and
without tobramycin by a factor of
eight.
Increase in the surface area of
antibiotic-impregnated cement spac-
ers has been shown to increase elu-
tion of antibiotic in vitro. Holtom et
al22 demonstrated that fenestrated
spacers with a 40% greater surface
area resulted in a 20% higher elution
rate of vancomycin from Palacos ce-
ment than from standard or donut-
shaped spacers. Masri et al23 demon-
strated a significant (P = 0.05) in-
crease in the elution of tobramycin
over 1 week with the use of Simplex-
impregnated blocks that had a 9%
increased surface area-to-volume
ratio.
Antibiotics in liquid form mixed
with cement dilute the catalyst that
is needed for the cement curing
process, thereby adversely affecting
both the curing time and final
mechanical properties of cement;
accordingly, they are not recom-
mended. Table 2 lists antibiotics
that can be mixed with cement.
In Vivo Studies
The penetration of antibiotics re-
leased from antibiotic-impregnated
cement into surrounding tissues has
been evaluated in both animal and
human studies. Concentrations of
antibiotic in hematoma, granulation
tissue, and bone vary according to
antibiotic. Local concentrations,
however, have been found to be
consistently higher than serum con-
centrations and usually exceed the
minimum inhibitory concentrations
for target pathogens.
The elution of several antibiotics
from Simplex cement was measured
in samples from dogs over a 28-day
period.24 Clindamycin, vancomy-
cin, and tobramycin exhibited elu-
tion characteristics that reached con-
sistently high levels in bone and
granulation tissue. Cefazolin and
ciprofloxacin were maintained at
high concentrations in granulation
tissue but at low levels in seroma
and bone. Ticarcillin showed unfa-
vorable elution characteristics in
granulation tissue, seroma, and
bone.
Experimentally produced para-
spinal wounds (fractured, infected
spinous processes) in rabbits were
treated with either a chain of to-
bramycin antibiotic-impregnated
cement beads, beads without antibi-
otics, systemic antibiotics only, or
nothing.25 At 5 days, no recoverable
organisms were found in six of eight
animals treated with antibiotic-
impregnated cement beads. Six of
eight rabbits receiving systemic
tobramycin had wound infections.
All five animals in which nonantibi-
otic-impregnated cement beads were
implanted had significant infections;
one died from sepsis. All four ani-
mals that received no treatment were
infected.
Antibiotic concentrations were
measured in wound drainage fluid,
urine, and serum from 50 patients
who underwent primary total hip
arthroplasty (THA) and received
tobramycin or vancomycin deliv-
ered either in antibiotic-impregnated
cement or by intravenous adminis-
tration (not both).26 No significant
differences were found between

Table 2
Antibiotics Used in Antibiotic-Impregnated Cement

Decreased
Activity Because Adversely Affected
Can Be Mixed With Cement of Cement Heat by Cement Curing

Amikacin Cefuzonam Erythromycin Penicillin Chloramphenicol Liquid gentamicin,

Amoxicillin Cephalothin Gentamicin Polymyxin B Colistimethate clindamycin, etc (because
Ampicillin Ciprofloxacin (powder) Streptomycin Tetracycline of aqueous content)
Bacitracin Clindamycin Lincomycin Ticarcillin Rifampin
Cefamandole (powder) Methicillin Tobramycin
Cefazolin Colistin Novobiocin Vancomycin
Cefuroxime Daptomycin Oxacillin

Vol 11, No 1, January/February 2003 41

Antibiotic-Impregnated Cement in Total Joint Arthroplasty
Simplex and Palacos surgeon-
prepared antibiotic-impregnated
cement. Serum and urine antibiotic
levels were significantly (P ≤ 0.05)
higher in the intravenous group
than in the impregnated-cement
group. Wound drainage fluid levels
of tobramycin were significantly (P
≤ 0.05) higher in the antibiotic-
impregnated cement group than in
the intravenous group, whereas the
vancomycin intravenous group had
higher antibiotic levels in wound
drainage fluid than did the van-
comycin cement group. In the
cement group, tobramycin exhibited
a consistently high level of bioactivity
against S epidermidis in wound
drainage fluid, while vancomycin
lost all bioactivity by 24 hours. In
30% of cases, no vancomycin was
detected in the wound drainage
fluid of the cement group. Overall,
tobramycin exhibited adequate local
tissue levels and released antibiotic
effectively, whereas vancomycin
exhibited inadequate elution prop-
erties.
Clinical Studies
Primary Total Joint
Arthroplasty
Because of the low rates of infec-
tion experienced with total joint
arthroplasty procedures, researchers
seeking to demonstrate statistically
significant differences with the pro-
phylactic use of antibiotic-impreg-
nated cement require a very large
sample size with multicenter partici-
pation. A prospective, randomized
study in Sweden combined results
from nine orthopaedics departments
(1,688 consecutive THAs) to com-
pare the prophylactic effect of
systemic antibiotics to that of genta-
micin-impregnated cement alone.
At a mean follow-up of 10 years, the
infection rate was 1.6% in the sys-
temic antibiotic group and 1.1% in
the gentamicin-impregnated cement
group, a difference that was not sta-
42
tistically significant.11 No cases of
nephrotoxicity, ototoxicity, or aller-
gic reaction were reported.
More than 10,000 primary ce-
mented total hip replacements done
for osteoarthritis and reported to the
Norwegian arthroplasty registry
were studied retrospectively.27 Four
groups were compared: patients
receiving antibiotic prophylaxis both
systemically and locally in antibiotic-
impregnated cement, those receiv-
ing antibiotics only systemically,
those receiving only antibiotic-
impregnated cement, and those
receiving no antibiotic prophylaxis.
The antibiotic-impregnated cement
was either Palacos with gentamicin
or AKZ (erythromycin and colistin
with Simplex). The rate of revision
done for any reason was 2.0%
(94/4,586) in patients receiving only
systemic antibiotics, 4.2% (10/239)
for antibiotic-impregnated cement
only, 1.2% (70/5,804) for the com-
bined regimen, and 2.5% (7/276) for
no antibiotics. Among cases that sub-
sequently required revision for in-
fection, the lowest revision rate,
0.14% (8/5,804), was in patients who
received both antibiotic-impregnated
cement and systemic antibiotics.
A prospective, randomized clini-
cal trial of 401 patients in two
British centers compared the effect
of cefuroxime-impregnated cement
and cefuroxime administered sys-
temically on infection after total
joint arthroplasty.28 No statistically
significant difference was found
between the two groups with
respect to incidence of superficial
wound infection or early deep infec-
tion (1% in both groups). There
were no late deep infections after 2-
year follow-up.
Hope et al29 found at least one
strain of gentamicin-resistant coag-
ulase-negative staphylococcus in 30
of 34 cases of deep infection (88%) in
which cement containing gentamicin
had been used. In contrast, only 9
of 57 patients (16%) in whom antibi-
otic-free cement was used exhibited
Journal of the American Academy of Orthopaedic Surgeons
gentamicin-resistant coagulase-neg-
ative staphylococcus.
Revision Arthroplasty
Revision arthroplasty usually is
accompanied by rates of infection
significantly higher than rates for
primary arthroplasty. Revision
arthroplasties done for infection are
either one- or two-stage procedures.
Two-stage revisions are more com-
mon, but they can be technically
demanding because of scar forma-
tion, limb shortening, disuse osteo-
porosis, and altered anatomy.
Although advocates of two-stage
reimplantation cite infection rates
lower than those of one-stage revi-
sions, carefully selected patients can
be treated with comparable success
with one-stage revisions using
antibiotic-impregnated cement. In
one review of the literature, success
rates of one-stage exchange with and
without the use of antibiotic-impreg-
nated cement were 81% and 71%,
respectively; the success rates of
two-stage reimplantation with and
without antibiotic-impregnated
cement were 93% and 82%.30
One-Stage Revision for Infection
One-stage exchange arthroplasty
using antibiotic-impregnated ce-
ment has been advocated in defined
instances for the treatment of an
infected total joint arthroplasty. In a
multicenter comparison of one- and
two-stage exchange arthroplasties
for infection conducted in the 1970s,
a success rate of approximately 80%
was found for both methods. 31
Gentamicin-loaded Palacos and 6
months of systemic antibiotics were
used in all procedures. The results
were slightly better for one-stage
exchanges; however, follow-up was
relatively short (0.5 to 3.5 years). In
a study of 235 one-stage exchanges
for THA infection using antibiotic-
impregnated cement, 11% with per-
sistent infection failed; another 3% of
cases with suspected infection
failed. 32 Of the 61 two-stage ex-
changes, which used antibiotic-

impregnated cement beads for peri-
ods of from 6 weeks to 9 months, 5%
failed from reinfection. Hope et al29
reviewed a series of 91 patients with
deep infection of a cemented
THA caused by coagulase-negative
staphylococcus. In this series, 72 pa-
tients were treated with one-stage
exchange arthroplasty; 9 (13%)
failed because of recurrence of infec-
tion. Gentamicin was used in com-
bination with other antibiotics based
on organism sensitivities. The other
19 patients underwent a two-stage
exchange without any failures.
Although it has been suggested
that a contraindication to one-stage
reimplantation is infection with a
gram-negative organism, a study of
15 patients with gram-negative
infection treated with one-stage
THA revision found only 1 recur-
rence (6.7%) at a mean follow-up of
8 years. Palacos cement with gen-
tamicin was used in 13 of 15 pa-
tients, with other antibiotics added
to cement as appropriate. 33 In a
larger study of 183 patients with
similar follow-up (mean, 7.75 years),
one-stage revision with both antibi-
otic-impregnated cement and sys-
temic antibiotics was used for deep
infection of a THA.34 Twenty-nine
of these patients (16%) had evidence
of persistent infection and 154 (84%)
were free of infection on follow-up.
None of the 29 patients who experi-
enced failure was infected with
gram-negative organisms.
For patients undergoing revision
arthroplasty, Garvin et al35 devel-
oped a classification system of
high-risk, suspicious, and definite
infection categories. These were
based on Gram stains, cultures,
intraoperative findings, clinical diag-
noses, radiographic findings, and
laboratory results.35 In a prospec-
tive clinical study, gentamicin-
impregnated Palacos was used for
prosthesis fixation in 67 high-risk,
32 suspicious, and 31 definite infec-
tions. All but one of the high-risk
patients underwent one-stage pro-
Vol 11, No 1, January/February 2003
cedures; those with suspicious or
definite infections underwent either
one- or two-stage procedures plus 6
weeks of intravenous antibiotics.
Postoperative infection occurred in
5 of the 92 one-stage patients (5.4%)
and in none of the 38 two-stage
patients. Of the 67 high-risk
patients, 3 (4.5%) developed post-
operative infections; one was then
revised with a successful two-stage
procedure. Of the 32 patients suspi-
cious for infection, 19 underwent
one-stage implantation; one of them
developed a postoperative infection.
The other 13 patients with suspi-
cious infection underwent success-
ful two-stage implantation. Of
patients with definite infection, 7 of
31 underwent one-stage implanta-
tion, with one of them developing a
postoperative infection; 24 patients
had a successful two-stage implan-
tation.
To test that one-stage revisions
can be successful if rigid criteria are
met, Ure et al36 prospectively fol-
lowed 20 consecutive patients under-
going one-stage THA for infection
between 1979 and 1990. Surgical
management included meticulous
débridement, use of antibiotic-
impregnated cement, and systemic
antibiotic therapy. Patients were
excluded from this treatment when
they were immunocompromised,
had an infection with a known resis-
tant gram-negative or methicillin-
resistant organism, or had a major
skin, soft-tissue, or osseous defect.
At a mean follow-up of 9.9 years, no
patient had experienced recurrence
of infection. Two patients required
revision for aseptic loosening.
Parenteral antibiotics were adminis-
tered postoperatively for a mean of
4.7 months.
Two-Stage Revision for Infection
By reducing dead space, cement
spacers help stabilize the limb
awaiting reimplantation (Fig. 1).
Complications include bone loss,
dislocation, continued pain, de-
creased mobility, and (rarely) frac-
Thomas N. Joseph, MD, et al
ture. Local antibiotic delivery with
cement spacers, cement beads, or a
PROSTALAC has been used after
component removal in a two-stage
procedure. Additionally, antibiotic-
impregnated cement can be used for
prosthesis fixation during reimplan-
tation in the second stage.
Antibiotic-impregnated cement
spacers used in the first stage of
two-stage reimplantation can deliv-
er a high concentration of antibiotics
to the infected area. In a retrospec-
tive study, Calton et al37 treated 25
infected total knee prostheses in 24
patients with débridement, compo-
nent removal, and insertion of an
antibiotic-impregnated cement block.
Intravenous antibiotics were admin-
istered for 6 weeks; patients’ knees
were kept immobilized with no
weight bearing. The success rate
was 92% (2 failures) at a mean fol-
low-up of 36 months; 15 of 25 knees
exhibited either tibial or femoral
bone loss caused by invagination of
the cement spacer block into the
cancellous bone. Leunig et al38 re-
ported on 12 patients with deep
infections of hip implants who un-
derwent two-stage revision and
were treated using gentamicin-
loaded cement. Spacers were used
for a mean of 4 months; during that
period, six spacers failed, five by
dislocation and one by fracture. At
a mean follow-up of 27 months after
reimplantation arthroplasty, all
patients were mobile and infection
free.
An articulating spacer used in
two-stage revision for infected total
knee arthroplasty may improve
patient mobility and allow partial
weight bearing. This would pro-
mote healthier soft tissues, improve
wound healing, allow easier reim-
plantation, improve bone quality
and range of motion, and reduce
complications. Hofmann et al 39
treated 26 patients who had late-
infected total knee arthroplasties
with two-stage revision using an
articulating spacer with tobramycin-
43
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
A B
Figure 1 Anteroposterior (A) and lateral (B) radiographs of an antibiotic-impregnated
cement spacer in a two-stage revision total knee arthroplasty.
impregnated cement. The spacer
was prepared by cleaning, autoclav-
ing, and reinserting the femoral
component. A new tibial polyethyl-
ene insert and in some cases a new
all-polyethylene patellar component
were used to place a large amount
of antibiotic-impregnated cement
between each insert and bone.
Patients were treated with 6 weeks
of intravenous antibiotic therapy.
Reimplantation was performed 6 to
12 weeks after placement of the
spacer. All but one patient (who
died of systemic complications)
underwent successful reimplanta-
tion (96%). At a mean follow-up
of 31 months, knee scores had
improved and no recurrence of in-
fection was found.
Complications of early articulat-
ing spacers included tibiofemoral
instability and patellar instability;
results subsequently have improved
with design modifications. A recent
study by Fehring et al 40 failed to
44
show any difference in range of
motion or knee scores between
articulating and static antibiotic-
impregnated cement spacers used
in two-stage revisions. The ar-
ticulating spacers were custom-pre-
pared using a stainless steel femoral
component mold and stemmed tibial
baseplate of antibiotic-impregnated
cement. Nevertheless, reimplanta-
tion was facilitated, and less bone
loss occurred with articulating spac-
ers than with static antibiotic-
impregnated spacers.
Lai et al41 reported on 40 infect-
ed hip prostheses treated with
component removal, intravenous
and oral antibiotics for 8 weeks,
and delayed reimplantation (mean,
48 weeks) with cementless compo-
nents. At mean of 4 years’ follow-
up, 5 patients (13%) had experi-
enced recurrent infection: 2 of 33
from the group treated with Sep-
topal (gentamicin) beads, and 3 of 6
of those treated without antibiotic-
Journal of the American Academy of Orthopaedic Surgeons
impregnated cement beads. A pro-
spective, randomized, multicenter
study of 6 infected total knee and 22
infected hip arthroplasties in 28
patients compared two-stage re-
implantation using gentamicin-
impregnated cement beads with
that using conventional parenteral
systemic antibiotic therapy for 6
weeks postoperatively.42 At a mean
follow-up of 3 years, infection
recurred in 2 of 15 patients treated
with gentamicin-impregnated
cement beads (13%) and in 4 of 13
patients treated with conventional
systemic antibiotic therapy (31%);
however, this was not statistically
significant. Whiteside43 used allo-
graft technique with cementless
revision arthroplasty for massive
tibial and femoral defects in 33
chronically infected total knee
arthroplasties. Treatment included
implant removal, débridement, and
rigidly fixed antibiotic-soaked bone
graft followed by 6 weeks of antibi-
otic-impregnated cement beads and
intravenous antibiotics. The success
rate of the two-stage procedure was
85%. Infection recurred in five knees;
however, repeated procedures al-
lowed successful revision in all but
one, which required an above-the-
knee amputation. Although use of
antibiotic-impregnated cement beads
or spacers is common in two-stage
revisions, one study showed that
their use in two-stage revisions was
not correlated with cure rate for
infection.44
The PROSTALAC, introduced in
1989, is a temporary hip prosthesis
composed of a thin polyethylene
acetabular cup and a stainless steel
femoral component, both of which
are loosely cemented with antibiotic-
impregnated cement (Fig. 2). Bene-
fits include early mobilization, accel-
erated rehabilitation, and early hos-
pital discharge. The device maintains
soft-tissue planes and leg lengths
and has made second-stage proce-
dures easier to perform. Younger et
al45 reviewed 48 patients who had

Figure 2 Anteroposterior radiograph of
the PROSTALAC in a two-stage revision
THA.
undergone two-stage arthroplasty of
an infected hip replacement using
the PROSTALAC. All but three pa-
tients were free from persistent
infection, for an eradication rate of
94%. More recently, Younger et al46
evaluated PROSTALACs with a
cement-on-cement articulation and
with a custom metal-on-polyethyl-
ene articulation. Of 28 infected total
hips followed for a minimum of 2
years, 96% exhibited no evidence of
infection.
In a retrospective study of 89 re-
vision procedures for infected total
knee arthroplasties, persistent infec-
tion occurred in 10 knees (11.2%).44
No standardized protocol was used
for treatment. In 64 knees, antibiotic-
impregnated cement was used for
implant fixation; in 25, no antibiotic-
impregnated cement was used.
Antibiotic-impregnated beads were
used in 20 patients, antibiotic-
impregnated spacers in 23, both
used in 4, and neither used in 42
patients. When use of antibiotic-
impregnated cement for implant fix-
ation was factored in, the results
were statistically significant. Of the
Vol 11, No 1, January/February 2003
25 knees without antibiotic-impreg-
nated cement, 7 (28%) developed
recurrent infection, compared with
only 3 (5%) of the 64 knees treated
with antibiotic-impregnated cement
(P < 0.01). Although antibiotic-
impregnated cement beads or spac-
ers appeared to be beneficial, their
use was not statistically significant.
We are not aware of any prospec-
tive randomized study comparing
antibiotic-impregnated cement
beads or spacers to antibiotic-
impregnated cement in prosthetic
fixation.
Antibiotics in Revision Arthroplasty
Without Infection
Although the use of antibiotic-
impregnated cement in revision
arthroplasty without evidence of
infection has been advocated, the
literature on the subject is scant and
equivocal. Lynch et al47 reported
notably better results with genta-
micin-containing cement for aseptic
revisions than with cement alone
(systemic antibiotics not used), a
reduction from 3.5% to 0.8%. A ret-
rospective analysis with minimum
2-year follow-up reported that in
aseptic revision THAs or conversion
from upper femoral prosthesis (pro-
phylactic systemic antibiotics not
used), infection rates were 0.5% for
gentamicin-impregnated cement
and 2.8% for cement alone.47 The
authors concluded that low-viru-
lence organisms that are difficult to
culture may be present in some
cases thought to be aseptic loosen-
ing and that the local antibacterial
effect is responsible for the effective
prevention and treatment of infec-
tion in these patients.
Experimental Cement-Antibiotic
Combinations
Ceramic composites have been
considered for use as a vehicle for
antibiotic delivery. In one laboratory
study of a novel bioactive bone ce-
ment (15% bisphenol-α-glycidyl
methacrylate, 15% triethylene-glycol
Thomas N. Joseph, MD, et al
dimethacrylate resin, and 70%
apatite- and wollastonite-containing
glass-ceramic powder) containing
cephalexin in the form of pellets,
antibiotic release was initially rapid,
slowed markedly after 24 hours, and
was released continuously thereafter
for 2 weeks.48 The strength of the
cement with cephalexin was approxi-
mately twice that of acrylic antibiotic-
impregnated cement. The authors
suggested that this material may be
suitable for prosthetic fixation as
well as in beads or spacers. Another
study tested the efficacy of a calcium
hydroxyapatite ceramic with gen-
tamicin in the form of blocks im-
planted adjacent to stainless steel
tibial inserts in rats that had been in-
jected with S aureus.49 Suppression
of infection in the ceramic-genta-
micin–treated animals was superior
to that in controls, including those in
which acrylic antibiotic-impregnat-
ed cement was used.
Biodegradable antibiotic-impreg-
nated material offers a potential
means of local antibiotic delivery for
infection control or treatment with-
out obligation for later removal. A
biodegradable cement (composed of
tricalcium phosphate and calcium
carbonate with a matrix phase of
polypropylene fumarate cross-
linked with methylmethacrylate
monomer) containing gentamicin
and vancomycin was evaluated for
treatment and prophylaxis of S
aureus osteomyelitis in rat proximal
tibias.50 The treatment group exhib-
ited significantly (P < 0.01) fewer
colony-forming units than did con-
trols. Sites treated prophylactically
developed no infections. No signifi-
cant difference was found between
biodegradable cement and PMMA
used as a carrier for antibiotics.
Another study showed that the ten-
sile strength of the material and the
biologic activity of the antibiotic
were maintained when gentamicin
was added to a resorbable calcium
phosphate cement composed of
β-tricalcium phosphate, monocal-
45
Antibiotic-Impregnated Cement in Total Joint Arthroplasty
cium phosphate monohydrate, and
water.51
More recently, calcium hydrox-
ide has been added to PMMA beads
containing tobramycin.52 The beads
released hydroxyl and calcium ions
into the culture medium as well as a
greater amount of antibiotic than
did beads containing only tobramy-
cin. Bacterial growth was more
effectively inhibited when S aureus
was incubated with tobramycin-
and calcium hydroxide–impregnat-
ed PMMA disks than with disks
containing only tobramycin. The
study did not, however, address the
effects of the tobramycin and calci-
um hydroxide combination on the
strength of the cement. Future uses
may include fracture healing and
bone grafting in addition to osteo-
myelitis treatment and implant
attachment.
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Summary
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47
 Advances in the Management of Humeral Nonunion

David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC

Abstract

Approximately 10% of all long-bone fractures occur in the humerus. Although union rates compared with earlier
primary treatment usually is successful, humeral nonunion can lead to marked techniques such as Kirschner wire
morbidity and functional limitation. Complications include joint contractures fixation.4
of the shoulder and elbow, especially with periarticular pseudarthrosis. Marked Humeral nonunions can be
osteopenia or bone loss, or both, often occur after fracture and after failure to grouped by the location of the
achieve union. Retained implants often break, impeding fixation and requiring injury (proximal, shaft, or distal)
removal. Soft-tissue deficits and incisions from the original injury or prior because each type has characteris-
surgeries also may complicate reconstruction, as can intra-articular fractures tics that dictate a specific treatment
and associated nerve palsies. Successful surgical management of humeral for a likely successful outcome.
nonunion requires stable internal fixation that allows early joint motion and Proximal humeral nonunions often
uses autogenous bone graft to promote healing. Contracture release and early are associated with shoulder joint
joint motion are necessary to optimize function. Shoulder hemiarthroplasty and contracture and rotator cuff dys-
semiconstrained total elbow arthroplasty are viable options for irreversible joint function, as well as osteopenia and
damage. Advances in preoperative evaluation and surgical reconstruction have a tendency for varus deformity.
improved functional outcomes. Diaphyseal nonunions that require
J Am Acad Orthop Surg 2003;11:48-59 surgery are often complicated by
existing hardware and bone loss.5
Nonunion of the distal humerus is
associated with significant elbow
Approximately 10% of all long- rates of 98% for closed and 94% joint contracture, synovial pseud-
bone fractures occur in the hu- for open fractures of the humeral arthrosis, poor bone condition,
merus.1 An increasing number of shaft after functional bracing. retained hardware, and ulnar neu-
these injuries are insufficiency or Locked humeral nails used for di- ropathy.6 Each of these complicat-
fragility fractures secondary to aphyseal fracture fixation were ing factors should be considered
osteoporosis, a result of the rise in designed in an attempt to improve during preoperative evaluation
age of the general population. union rates for injuries that re- and when assessing surgical op-
Despite advances in the initial man- quired surgery. They could poten- tions.
agement of these fractures, some tially minimize morbidity and
result in nonunion, requiring fur- allow earlier patient mobility
ther intervention. The factors that compared with open plating tech-
contribute to the incidence of non- niques. A recent review of com- Dr. Pugh is Clinical Fellow, Upper Extremity
Reconstructive Service, St. Michael’s Hospital
union include patient age, mecha- plications associated with intra-
and the University of Toronto, Toronto, ON,
nism of injury, initial treatment, medullary nailing of humeral Canada. Dr. McKee is Associate Professor,
presence of concomitant injuries, shaft fractures suggests that the Upper Extremity Reconstructive Service, St.
nutritional status, and a history of theoretic benefits of locking hum- Michael’s Hospital and the University of
smoking.1 eral nails have not been supported Toronto.
Because treatment is time con- by prospective trials.3 Distal hum-
Reprint requests: Dr. McKee, Suite 800,
suming and difficult, successful eral fractures routinely require
55 Queen Street E, Toronto, ON, Canada
initial fracture management is surgical intervention; double-plat- M5C 1R6.
important. Most humeral shaft ing these fractures using implants
fractures can be treated nonsurgi- perpendicular to each other has Copyright 2003 by the American Academy of
cally with a high rate of union. markedly increased the rigidity of Orthopaedic Surgeons.
Sarmiento et al 2 described union the fixation and decreased non-

48 Journal of the American Academy of Orthopaedic Surgeons

 David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC

Proximal Humeral is important to do an extensive ously thought.9 Traction at the frac-

Nonunion release of the rotator cuff, which ture site, inadequate immobilization
will be contracted and shortened or fixation, and premature motion
Approximately 40% of all humeral because of the malposition of the all contribute to the development of
fractures occur in the proximal tuberosity. The defect in the proxi- nonunion. The most important
humerus. They occur most fre- mal humerus should be débrided determination is whether the hu-
quently in the elderly (≥65 years) and the tuberosity reattached to its meral head is salvageable (Fig. 1,
and generally unite within 6 weeks. native location using cancellous A). Complicating factors include
Malunion is more common than screws with washers. Augmenta- varus deformity from the unop-
nonunion; the small number of pa- tion of the fixation is often possible posed pull of the rotator cuff, severe
tients whose fractures do not heal using a nonabsorbable suture osteopenia, avascularity of the head
are typically symptomatic and have through the rotator cuff tied as a or neck fragment, and severe joint
poor shoulder function. The use of tension band to the proximal hu- stiffness. The joint surface of the
hanging casts, skeletal traction, and meral shaft. If the tuberosity is humeral head usually is well pre-
the occurrence of severely displaced fragmented or is too small to allow served. In younger (<65 years),
or “four-part” fractures are the most fixation, the fragments should be active patients, the nonunion should
important risk factors for develop- excised and the rotator cuff mobi- be repaired whenever possible;
ing nonunion.7-10 lized and repaired to a bony trough fixed-angle devices for the proximal
at the articular margin. Rehabilita- humerus have improved the ability
Greater Tuberosity tion is similar to that required for to do so. In older patients, hemi-
Closed treatment of greater tu- rotator cuff repair. arthroplasty is indicated for severe
berosity fractures may result in pos- degenerative changes of the articu-
terior and superior migration of the Neck lar surface, osteonecrosis of the
fracture fragment.11 Although dis- Nonunion after surgical neck frac- humeral head, or osteopenia severe
placement of <1 cm is well tolerated, tures is more common than previ- enough to jeopardize fixation.10
greater displacement may result in
subacromial impingement and rota-
tor cuff dysfunction (because of
shortening of the musculotendinous
units of the rotator cuff) and greater
prominence of the tuberosity. Even
though malunion is more common
than nonunion, surgical reconstruc-
tion is indicated in patients present-
ing with pain or functional limitation
attributable to proximal migration of
the greater tuberosity fragment.
Standard anteroposterior, lateral,
and axillary radiographic views of
the shoulder usually do not show
the bony structure adequately; a
computed tomography scan is nec-
essary to determine the exact loca-
tion of the fragment.
Surgical reconstruction should be
done with the patient in a beach
chair position using a deltoid-split-
A B
ting approach to expose the proxi-
mal-lateral humerus. Acromioplasty Figure 1 A, Anteroposterior radiograph showing nonunion of the humeral neck in a
can be performed concurrently if 48-year-old diabetic woman. The proximal fragment is osteoporotic and tipped into
impingement is exacerbating symp- varus; this indicates reasonable vascularity from the attachment of the rotator cuff.
B, Postoperative anteroposterior radiograph after correction of the deformity, release of
toms. Internal rotation of the arm the subacromial adhesion, application of the proximal humeral blade plate, and addition
helps to expose the tuberosity; once of an iliac crest bone graft. Healing was uneventful.
the fracture fragment is identified, it

Vol 11, No 1, January/February 2003 49

Management of Humeral Nonunion
For primary salvage of a humeral
neck nonunion, a blade plate tech-
nique can provide optimal stability.
It allows sufficient purchase in the
humeral head, and the fixed-angle
implant minimizes the risk of varus
collapse of the proximal humerus
that occurs with the use of standard
plates, in which the screw-plate
angle is not fixed. The patient is
placed in a semiseated position with
the arm draped free in the surgical
field. Through a deltopectoral ap-
proach, the nonunion site is identi-
fied and débrided. A release is
done at the nonunion site to allow
proper realignment. The intramed-
ullary canal is recreated, and autog-
enous bone graft is added. Release
of subacromial and periarticular
adhesions improves motion and
helps decrease stress on the implant.
To reduce the risk of impingement
from hardware, the insertion site
should be just distal to the level
of the greater tuberosity. To aug-
ment stability of the implant proxi-
mally, a screw can be placed into
the head fragment adjacent to the
blade, creating a triangular con-
struct (Fig. 1, B). If anatomic condi-
tions are favorable, the screw may
be inserted in a lag fashion. To neu-
tralize the deforming force of the
rotator cuff, a nonabsorbable suture
can be placed through it and tied as
a tension band around one of the
screw heads distal to the nonunion.
Postoperatively, patients should
be managed with early pendular
and active-assisted exercises, begin-
ning on day 1. A sling may be used
for comfort. Full active abduction
and flexion should be started at 6
weeks postoperatively, and resistive
or strengthening activities initiated
with evidence of bony bridging
(typically, 8 to 12 weeks). A high
rate of union can be achieved when
this technique is combined with the
liberal use of autogenous bone graft
and rotator cuff repair (if necessary).
In one series,12 union was achieved
in 23 of 25 proximal humeral non-
50
unions, with an accompanying im-
provement in function. The Dis-
abilities of the Shoulder, Arm and
Hand (DASH) score was used to
evaluate the patients (0 = normal
function, 100 = complete disability).
The mean DASH score improved
from 77 to 21 points. Patients expe-
rienced a notable improvement of
pain levels and were able to per-
form light activities of daily living
and personal hygiene at or slightly
above the head level.
An alternative method of obtain-
ing fixation in the osteoporotic
humeral head is to contour a plate
into a blade configuration, using the
last hole in the blade portion of the
plate to insert a locking screw from
the shaft of the plate. This creates a
truss construct that is biomechani-
cally superior to a standard plate
and helps reduce the toggle of
screws.13
For patients not undergoing pri-
mary repair, a hemiarthroplasty typ-
ically is done with a deltopectoral
approach. Any implanted hardware
is removed and existing tuberosities
are identified. An arthrotomy can
be done or, alternatively, the joint
entered between the tuberosities if
they are malunited or nonunited.
The humeral head is then resected,
although the distortion of proximal
anatomy can make it difficult to use
standard cutting jigs. The humeral
head osteotomy may need to be
done freehand. Reaming the canal
and inserting the humeral stem can
be difficult if translational malunion
has resulted between the shaft and
tuberosity, making them noncolin-
ear. Also, the tuberosities may be
malunited in a varus fashion, im-
peding a direct approach down the
humeral canal. Preoperative assess-
ment is critical because, rather than
undergoing a standard arthrotomy,
the tuberosities must be osteoto-
mized so that they may be reposi-
tioned. If the humeral stem is to be
cemented, care must be taken to
avoid leakage through any screw
Journal of the American Academy of Orthopaedic Surgeons
holes from previous fixation in the
shaft.
The technical challenges and
higher infection rates are two rea-
sons that hemiarthroplasty after
failed primary treatment of proxi-
mal humeral fractures is a compli-
cated procedure. Hemiarthroplasty
routinely yields poor results com-
pared with those of primary arthro-
plasty done for fracture or arthritis.
In a series of 23 patients who under-
went arthroplasty for salvage of dis-
placed proximal humeral fractures,
Norris et al10 reported pain relief in
95%, but only 53% could perform
activities at or above shoulder level.
While pain relief is obtainable, re-
storing motion (especially over the
head) is far from assured and de-
pends on the proper positioning of
the tuberosities and the integrity
of the rotator cuff. Therefore, fixa-
tion of the nonunion is the preferred
treatment, especially in young
patients.
Shaft
Humeral diaphyseal fractures
account for approximately 30% of
all humeral fractures.1 Nonunion
of the humeral shaft occurs in 2% to
10% of nonsurgically treated frac-
tures and in up to 15% of fractures
treated by primary open reduction
and internal fixation (ORIF).1,2,14,15
Union should occur within 12 to 16
weeks; nonunion is defined as a
lack of union within 24 weeks. 15
Although troublesome in young
patients, humeral shaft nonunion
can have a severely deleterious ef-
fect on the independence of older
patients.
Increased incidence of nonunion
is associated with open fractures,
high-impact injuries, bone loss or
fracture gapping, soft-tissue inter-
position, unstable fracture patterns,
segmental fractures, impaired blood
supply, infection, and initial treat-
ment with traction or a hanging

cast.1 Preexisting shoulder or elbow
stiffness can result in increased
motion at the fracture site and thus
predispose patients to nonunion.
Patient factors such as obesity,
osteoporosis, alcoholism, malnutri-
tion, and noncompliance also are
influential.1,14,15 Nutritional status
and smoking habits should be
improved before initiating surgical
treatment.
The preoperative assessment
should include a complete history,
especially evaluating for any symp-
toms of current or previous infec-
tions. A physical examination of the
involved limb is required to detect a
prior or active draining sinus; un-
usual erythema or induration of the
skin; or tender, swollen axillary
lymph nodes. Low-grade infections
can be difficult to diagnose from the
history and physical examination
alone; therefore, laboratory tests
should be done preoperatively.
Basic blood tests should include a
complete blood count, white blood
cell (WBC) count, C-reactive protein
(CRP) level, and erythrocyte sedi-
mentation rate (ESR). These tests
are sensitive, and a normal CRP
level and ESR indicate a low likeli-
hood of clinically relevant infec-
tion.16 Patients with elevated values
should be assessed further with gal-
lium 67 bone scintigraphy and, ide-
ally, an aspirate of the nonunion site
for culture.16 A positive culture can
help direct antibiotic treatment
(both locally and systemically).
Unexplained anemia or a cachectic
appearance may indicate a nutri-
tional deficiency that should be cor-
rected before surgery. Testing for
serum protein or albumin levels
also may be indicated in such pa-
tients.
In an established humeral shaft
nonunion, the salient symptom is
functional loss. Although nonunion
typically is not as painful as in the
lower extremity, the lack of mechan-
ical stability precludes repetitive
motion, resistive work, or heavy lift-
Vol 11, No 1, January/February 2003
David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC
ing with the involved upper extrem-
ity. In patients with poor intrinsic
stability, a flail arm may interfere
with personal hygiene, dressing,
and simple activities of daily living.
In older patients, the functional dis-
ability from a humeral nonunion
can be severe enough to interfere
with living independently.
Nonsurgical treatment of hu-
meral shaft nonunion may be ap-
propriate in certain situations. In
older patients, the presence of sig-
nificant osteoporosis or medical
comorbidity can make anesthesia
and surgical reconstruction particu-
larly difficult. If only minimal dis-
comfort is present, application of a
lightweight orthosis may provide
enough stability to achieve an ac-
ceptable level of function. In certain
settings (eg, no infection, no bone
loss), noninvasive treatment, includ-
ing electrical stimulation, ultra-
sound, and extracorporeal shock
wave therapy, has been used with
varying rates of success.17 Given
the high success rate of current
treatment methods, however, sur-
gery is indicated for most patients.
The goal of surgery is to achieve
stable internal fixation and institute
early motion. Although a variety of
techniques has been described,
including locking intramedullary
nails, unilateral external fixators,
and circular external fixation, the
preferred treatment is compression
plating with the addition of autoge-
nous iliac crest bone graft, as the
success rate has been high. 5 The
mechanical and biologic features of
the nonunion have a direct bearing
on the optimal surgical treatment.
For hypertrophic nonunions, estab-
lishing mechanical stability alone is
usually sufficient to allow healing
without the need for additional
bone grafting. Atrophic nonunion,
on the other hand, indicates a sub-
optimal healing response that re-
quires the addition of a biologic
stimulus, such as an autogenous
bone graft, and stable internal fixa-
tion. The presence of infection or
marked bone loss (>4 cm) indicates
a need for change in the reconstruc-
tive technique.
Surgical Technique
An anterolateral approach that
allows extension both proximally
and distally usually can be used. A
posterior approach is reserved for
nonunion of the distal humerus in
which insufficient length is avail-
able for three or four screws distally
above the olecranon fossa. In such
cases, a posterior approach is pre-
ferred in order to apply two (small
fragment) plates distally along the
medial and lateral columns to
enhance fixation.
With an anterolateral approach
for a nonunion in the proximal
shaft, the deltoid insertion can be
protected by twisting the plate so
that distally it lies anterior to the
deltoid insertion and proximally lies
lateral to the biceps tendon. This
may be preferable when preserva-
tion of deltoid strength and function
is critical, such as when there is con-
comitant inferior pseudosubluxa-
tion of the humeral head (which is
exacerbated by deltoid dysfunc-
tion).18 In general, the anterior por-
tion of the deltoid insertion can be
reflected, if necessary, with minimal
functional consequence. For mid-
shaft or distal shaft nonunions, the
radial nerve is identified between
the brachialis and brachioradialis
muscles, and an external neurolysis
is done to isolate and protect the
nerve throughout. In atrophic non-
unions or those with an established
synovial pseudarthrosis, the non-
union site is exposed and débrided
to healthy, bleeding, viable bone.
Any synovial tissue at the nonunion
site must be resected. The intra-
medullary canal also should be
reestablished because it is an excel-
lent source of osteoprogenitor cells.
Sufficient dissection and release is
done to allow correction of any
deformity and to obtain apposition
51
Management of Humeral Nonunion

of the bone ends. It may be neces-
sary to shorten the humerus to pro-
vide end-to-end bony contact; loss
of up to 3 or 4 cm in length does not
appear to have any notable detri-
mental functional effects. Short-
ening >4 cm is not desirable from
either a functional or cosmetic
standpoint; other methods to treat
the defect are necessary.
The pathologic features of the
nonunion fracture fragments can be
used in the surgical technique. If
possible, two oblique surfaces can
be fashioned and a lag screw placed
across the nonunion to facilitate
compression. Otherwise, compres-
sion is achieved by inserting the
plate in compression mode. A 4.5-
mm compression plate placed later-
ally or anterolaterally with stag-
gered holes allows the surgeon to
avoid inserting screws in a single
longitudinal plane, which can lead
to fissuring or splitting of the bone.
At least four screws (eight cortices)
should be used above and below
the nonunion, or three screws (six
cortices) if a solid lag screw has
been applied. When bony débride-
ment has been extensive and the
defect at the nonunion site is greater
than that which can be accommo-
dated by compression with the
plate, the external device can be
used to close the gap and apply
compression. Liberal use of autoge-
nous bone graft or another osteoin-
ductive agent is imperative in atro-
phic, biologically inactive situations.
anterolaterally, as in a humerus
with varus deformity). Compression
is achieved by sequential insertion
of the screws proximally to distally
relative to the nonunion site; pulling
the shaft up to the straight, uncon-
toured plate; and correcting the
deformity. The broad surfaces of the
nonunion usually allow placement
of lag screws for additional compres-
sion and stability. Newer plate
designs that have undercut holes
allow insertion of screws at steeper
angles, which facilitates lag screw
insertion through the plate. Bone
graft in this situation is not necessari-
ly required (Fig. 2).
Infection
Infected nonunion of the humerus
is a difficult challenge. The nature
of the surgical intervention depends
on the condition of the patient, the
infecting organism or organisms,
and local conditions at the non-
union site. Initial studies should
include a history, physical examina-
tion, and basic blood tests, includ-
ing WBC, CRP level, and ESR. If the
diagnosis is not established, a gal-
lium 67 bone scan can confirm the
presence of infection. 16 Previous
cultures or an aspirate can identify
the infecting organism or organisms
and direct treatment. Antibiotics
are withheld preoperatively to
avoid compromising definitive deep
intraoperative cultures. This is fol-
lowed by a thorough débridement
and irrigation. Immediate fixation
can be done in a healthy patient (eg,
with no cancer or immunodeficien-
cy, nondiabetic, nonsmoking) with a
single, nonvirulent organism (eg,
Staphylococcus epidermidis) and good
soft-tissue coverage. Fixation can be
optimized at the nonunion site with
antibiotic-impregnated calcium sul-

Hypertrophic Nonunion
Hypertrophic nonunion usually
occurs when nonsurgical care fails
in the setting of a vigorous healing
response and poor mechanical envi-
ronment, or after surgery with inad-
A B C
equate fixation. Generally, this type
of nonunion requires mechanical Figure 2 A, Anteroposterior radiograph of humeral shaft nonunion in a 37-year-old
stability and compression to obtain woman 14 months after treatment with bracing. Anteroposterior (B) and lateral (C) radio-
union. It does not need to be dé- graphs 4 months after ORIF with a broad 4.5-mm compression plate and a lag screw
(through the plate), showing solid union. The nonunion was not “taken down” or bone
brided but instead should be treated grafted. Given the biologic response and callus at the fracture site, it was anticipated that
with a broad 4.5-mm plate on the stable fixation and compression would be adequate to achieve union.
convex side of the bone (typically

52 Journal of the American Academy of Orthopaedic Surgeons

 David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC

fate, which elutes a tremendously cular injury, even in experienced tissue, reestablishment of the intra-
high local concentration of antibi- hands (5% to 19%), and refracture medullary canal, graft interposition
otics and is osteoconductive, or with after frame removal (13%).20 with stable fixation, and cancellous
antibiotic-impregnated methyl- autografting at both ends of the
methacrylate cement beads.16 Bone Loss interpositional graft.
In the absence of these condi- When extensive segmental bone Another method that can be used
tions, the nonunion should be stabi- loss has occurred, either as a result to treat atrophic nonunions with
lized with an external fixator fol- of the initial injury or because of bone loss is the waveplate technique
lowed by serial débridements, dur- extensive débridement, advanced recently described by Ring et al.24
ing which repeat cultures should be treatment techniques are needed. A The plate is an integral part of a
taken. To assist in creating an opti- defect of 3 to 4 cm can undergo technique designed to limit dissec-
mal environment for infection con- acute shortening and plate fixation. tion, preserve local blood supply,
trol, placement of an antibiotic bead For greater bone loss, other recon- bridge the nonunion gap, and pro-
pouch with antibiotic-impregnated structive options should be consid- vide abundant local cancellous bone
bone substitute or bone cement is ered. These include vascularized graft to stimulate healing. The
beneficial. 16 When the wound is fibular transfer (Fig. 3), corticocan- wave in the plate at the level of the
clean and dry and laboratory test cellous autografts, humeral allo- nonunion may provide some me-
(ESR and the CRP level) results have grafts, or bone transport using a chanical advantage to the nonunion,
returned to normal (typically circular fixator.19-23 Each method re- although results are inconclusive.
between 6 and 12 weeks postopera- quires débridement of all nonviable Ring et al24 reported healing in 14 of
tively), definitive fixation with com-
pression plating and bone grafting
can be done. If a bony defect is pres-
ent, any grafting procedure should
be delayed until the infection is
eradicated. Ambiguous cases are
evaluated with repeat aspiration of
the nonunion site for culture.
Another treatment option for
infected nonunion of the humeral
shaft is the application of a circular
fixator. Indications include osteo-
penic bone, failed conventional sur-
gery, and anticipated difficulty in
eradicating infection (ie, a compro-
mised patient, presence of a virulent
organism, or both). This technique
can provide stable fixation even in
the presence of osteopenia or bony
defects, and it has the advantage of
not requiring any implanted metal-
lic devices at the nonunion site.
Compression is applied through the
frame, and bone grafting usually is
not necessary, although some short-
ening may occur at the nonunion
site. Patel et al19 reported healing in A B
15 of 16 patients treated in this man-
Figure 3 A, Anteroposterior radiograph of a humeral shaft nonunion with extensive di-
ner (all had failed previous sur- aphyseal bone loss after a high-velocity gunshot wound complicated by infection in a 53-
gery). Lammens et al 20 reported year-old woman. The size of the defect is too great for shortening or nonstructural bone
success in 28 of 30 patients. Disad- graft. B, Postoperative anteroposterior radiograph showing reconstruction with vascular-
ized fibular graft, autogenous iliac crest bone grafting of the junction sites, and plate fixa-
vantages include the length of time tion. After 6 months of healing, arm function improved dramatically. This specialized
in the frame (a mean of 6 to 8 technique is appropriate for patients with defects ≥5 cm.
months), the potential for neurovas-

Vol 11, No 1, January/February 2003 53

Management of Humeral Nonunion

15 patients (mean preoperative requiring removal; and numerous Union rates after surgical repair
bony defect, 3 cm). pin tract infections. Although this using compression plating and bone
method seems to be an attractive grafting are excellent, ranging from
Nonunion After Locked option, the specialized technique 83% to 100%, with a high rate of
Humeral Nailing and high complication rate may patient satisfaction.5,13,15,24,25 Otsuka
The first generation of intramed- limit its general use. et al5 reported success in 25 of 25
ullary devices for fixation of humeral shaft nonunions treated
humeral fractures involved consid- Results with compression plating. They
erable problems with rotational and Union rates of 0% to 60% have also noted that the prognosis after
axial instability, nail migration, and been reported with noninvasive surgical repair of a humeral shaft
insertion site discomfort. Locked methods such as ultrasound or elec- nonunion depends on a number of
nails were designed to ameliorate trical stimulation. 15,17 The ideal factors, some of which are beyond
some of these problems but, unfor- patient for these therapies has a sta- the control of the surgeon. Otsuka
tunately, nonunions still occur ble, straight, noninfected delayed et al5 suggested that the presence of
despite these implants. Surgeons union or nonunion, with no bone loss, comorbid factors (ie, medical,
often are faced with a considerable that requires biologic intervention to medicolegal) had a notably negative
reconstructive dilemma when heal.15,17 Such patients are rare. effect on scores on the Medical
nonunion is associated with a failed
locked humeral nail (broken nails or
screws). Nail removal through the
rotator cuff can compromise post-
operative function. Bone loss, often
sufficient to compromise cortical
integrity, commonly occurs at the
nonunion site and in the distal
humerus around a loose nail. Ex-
change nailing of these injuries gen-
erally does not provide a reliable
means of obtaining union. In a ret-
rospective multicenter review, 25
only 4 of 10 patients achieved union
with exchange nailings, whereas 9
of 9 did so with conversion to plate
fixation with autogenous bone
grafting (Fig. 4). Robinson et al26
reported success in only two of five
cases of exchange nailing after
unsuccessful Seidel nailing.
Patel et al 19 recently described
the use of the Ilizarov technique to
treat humeral shaft nonunion. In 10
patients with nonunion after in-
sertion of large-diameter humeral
nails, the authors left the nail in situ,
removed locking screws (if present),
applied a circular fixator, and com- A B
pressed the nonunion site with the
frame. They reported healing in all Figure 4 A, Anteroposterior radiograph showing diaphyseal nonunion after failure of a
Seidel nail. Note the bone loss around the distal end of the nail (arrow). With a loose nail,
10 patients (mean time to union, 4 this can be severe enough to jeopardize cortical continuity and screw purchase. B, Recon-
months), but the complication rate struction consisted of removing the nail and locking screw, performing blade plate fixa-
was high. There were three patients tion, and applying autogenous iliac crest bone graft. A blade plate was used because of
the poor proximal bone quality after nail removal. (Reprinted with permission from
with temporary nerve palsies; three McKee MD, Miranda MA, Riemer BL, et al: Management of humeral nonunion after the
cases of excessive shortening (4 cm, failure of locking intramedullary nails. J Orthop Trauma 1996;10:492-499.)
7 cm, and 8 cm); nail protrusion

54 Journal of the American Academy of Orthopaedic Surgeons


Outcomes Study 36-Item Short
Form, which measures general
health status, but had no effect on
the joint-specific Constant (shoul-
der) 27 or Mayo (elbow) 28 scores.
Although patients typically im-
prove with successful surgery, it
may be impossible to provide a
“normal” state if significant comor-
bidity is present. Otsuka et al5 also
showed that the duration of the
nonunion has no effect on ultimate
functional or joint-specific scores
after successful treatment.
It is difficult to accurately deter-
mine the prognosis for humeral
nonunion complicated by infection,
segmental bone loss, or poor pa-
tient nutrition. Information must
be determined from larger studies
of general humeral nonunion.
Excellent union rates (88% to 95%)
can be anticipated when principles
of infection eradication are fol-
lowed or when specialized tech-
niques such as fibular grafting or
circular fixation are used. 19,20,22
Inappropriate application of hard-
ware or bone graft, or both, to an
infected nonunion site should be
avoided. In most studies, patients
who abuse alcohol are overrepre-
sented in the group of patients with
complications because of factors
common in this population. These
include prevalence of falls, postop-
erative withdrawal symptoms with
delirium or seizures, severe osteo-
penia, malnutrition, and heavy cig-
arette smoking.15,22
Distal Humeral Nonunion
Only 20% to 30% of humeral frac-
tures involve the distal aspect of the
bone. 21 During the past two de-
cades, advances in implants and
surgical techniques, and recognition
of the importance of early motion
postoperatively, have resulted in
immediate ORIF being the standard
of care for displaced fractures.
Nevertheless, the incidence of non-
Vol 11, No 1, January/February 2003
David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC
union is still as high as 10% after
ORIF, most commonly because of
inadequate fixation.4,29 Other factors
that predispose to nonunion include
open fractures, fracture comminu-
tion, high-energy injuries, and in-
fection. The incidence of nonunion
appears to be higher in elderly
women. 21,30 In fractures treated
nonsurgically, premature motion
also is responsible for nonunion.
Distal humeral nonunion is very
disabling. In addition to symptoms
of pain, decreased range of motion,
and poor function, patients often
have associated ulnar neuropathy.31
Instability and weakness also are
common. 32 In planning surgical
treatment, patient factors such as
age, medical status, previous sur-
gery and associated scars, adequacy
of the soft-tissue envelope, and the
presence of other upper limb dis-
abilities should be considered.
Quality of bone stock, presence
of articular disease, degree of joint
contracture, and severity of defor-
mity are important limb factors to
consider. A successful outcome
from osteosynthesis requires ade-
quate bone stock and minimal artic-
ular degeneration; in addition, joint
contracture (which is almost always
present) must be correctable.
Arthroplasty should be considered
for poor bone stock, severe deformi-
ty, or irreversible joint disease.
Arthrodesis is appropriate for
patients with nonreconstructable
joints who are not eligible for
arthroplasty because of infection or
concerns about compliance. Arthrod-
esis also is a reasonable option in
young, active patients whose non-
union is complicated by irreversible
joint damage, bone loss, or infection.
However, elbow arthrodesis is
extremely limiting functionally and
should be considered a salvage pro-
cedure with the limited goals of sta-
bility and pain relief.
Careful evaluation of the soft-
tissue envelope is necessary before
surgery. It is quite common for a
patient to have undergone numer-
ous surgeries of the elbow, often
through a number of incisions. In
rare cases, tissue expansion can be
done as a staged procedure to allow
for appropriate coverage; or local
rotational flaps or even free flaps
may be required, which influences
the choice of planned bony recon-
struction. The neurologic status of
the limb must be evaluated careful-
ly; preoperative electromyographic
studies can help determine if local
nerve compression should be treat-
ed surgically. Ulnar nerve palsy
resulting from scarring and fibrosis
after failed primary fracture care is
common; it is important to deter-
mine whether ulnar nerve transpo-
sition has been done. Ulnar nerve
recovery is advisable after adequate
release and neurolysis in these pa-
tients, although it may take up to 2
years for intrinsic muscle strength
and bulk to return.33
Surgical Technique
The patient is positioned in the
lateral decubitus position with the
affected arm placed over a bolster.
A sterile tourniquet is useful to
allow more proximal exposure, if
necessary. A long (15 to 25 cm),
midline posterior incision is made,
with previous incision lines incorpo-
rated, if possible. The ulnar nerve is
identified proximally, and an exter-
nal neurolysis is done to mobilize
the nerve. The nonunion usually is
between the capitellum and trochlea,
or between the metaphyseal and
diaphyseal fragments, and can be
approached by splitting the triceps
longitudinally. Alternatively, the
olecranon can be osteotomized and
the triceps reflected proximally.
The nonunion is identified and the
bone ends débrided. Injuries of the
distal humerus commonly are asso-
ciated with significant joint contrac-
ture with arthrofibrosis. An exten-
sive joint release should be done,
clearing the olecranon fossa and
removing any osteophytes. The an-
55
Management of Humeral Nonunion

terior capsule can be approached
through the nonunion site or by dis-
secting around the lateral side and
entering through a separate antero-
lateral arthrotomy site.
Provisional fixation of the non-
union is obtained with Kirschner
wires. Definitive fixation consists of
two plates oriented at 90° angles to
each other. The preference is to use
a 3.5-mm reconstruction plate pos-
teromedially and a precontoured J
plate directly laterally.4 As much
distal fixation as possible is ob-
tained. For very distal nonunions,33
it is sometimes necessary to use a
third plate posterolaterally. Autog-
enous bone graft from the iliac
crest is used liberally. The olecra-
non osteotomy is fixed using a pre-
drilled 6.5-mm cancellous screw
with a tension band, and an anterior
subcutaneous transposition of the
ulnar nerve is done (Fig. 5). Ar-
ticulated hinge fixators generally
are not necessary because both the
medial and lateral collateral liga-
ments (with their origins on the dis-
tal fragment) are intact. Joint stabil-
ity is maintained if appropriate care
is taken during the procedure.
Early motion is instituted on the
first postoperative day. Unless the
olecranon or triceps needs to be pro-
tected, full active motion is initiated
under the supervision of a physio-
therapist. Extension splinting is
often beneficial to decrease the risk
of flexion contracture. Continuous
passive motion, especially in associ-
ation with axillary block analgesia,
is used for severe or recurrent con-
tracture. Because anti-inflammatory
medications such as indomethacin
may be detrimental to fracture
healing, they should not be used
routinely for prophylaxis against
the development of heterotopic
bone.34
Open Reduction and Internal
Fixation
Osteosynthesis remains the treat-
ment of choice in young patients
with good bone stock. In 1982,
Mitsunaga et al30 reported their 10-
year experience with 25 patients,
who achieved an 88% union rate
(average time to healing, 7.7
months). Twenty-four percent of
the patients needed additional sur-
gery to achieve union. Complica-
tions of nerve palsy or infection
were noted in four patients. Al-
though the authors showed that
union could be obtained, the aver-
age increase in range of motion was
only 9°. The authors correctly con-
cluded that the goals of union and
motion are often in conflict and that
stable fixation allows shorter peri-
ods of immobility and may lead to
better motion.30
In another series of 20 patients
with distal humeral nonunion, 17
were treated surgically, with 15
undergoing ORIF and autogenous
bone grafting.21 Union was achieved
in 94%, with an average elbow flex-
ion-extension arc of 74°. Complica-
tions were limited to one radial
nerve palsy that spontaneously re-
covered within 2 months and an
infected distal humeral allograft
that required débridement and
reimplantation of a second allograft.
Overall function was rated excellent

A B C D

Figure 5 Anteroposterior (A) and lateral (B) radiographs of a distal humeral nonunion in a 68-year-old man after nonsurgical treatment
of a transcondylar fracture. There is minimal deformity, reasonable distal bone stock, and no degenerative change, which made the
nonunion appropriate for reconstruction. Anteroposterior (C) and lateral (D) radiographs after reconstruction using stable fixation with
contoured plates on the medial and lateral columns, autogenous bone grafting, and joint contracture release through a posterior approach.
At 1 year postoperatively, elbow motion measured 25° to 13°, and the nonunion was united.

56 Journal of the American Academy of Orthopaedic Surgeons

 David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC

in one patient, good in six, fair in
seven, and poor in six. The authors
recognized the importance of rigid
internal fixation with the addition of
autogenous bone graft as an adjunct
to obtain bony union. They also
concluded that the presence of intra-
articular nonunion or associated
severe soft-tissue trauma was a poor
prognostic factor.21
In 1994, McKee et al6 reported on
a series of 13 patients with distal
humeral nonunion or malunion.
Surgery in all cases involved an
extensile exposure, mobilization,
and transposition of the ulnar
nerve; external neurolysis, when
necessary; anterior and posterior
capsulectomy; articular defect
reconstruction; rigid fixation with
plates; iliac crest bone grafting;
and a postoperative protocol that
stressed early motion. Union was
achieved in all patients, with a
mean increase in motion arc from
45° preoperatively to 97° postopera-
tively (mean follow-up, 25 months).
No notable complications occurred.
The improved results can be attrib-
uted to the application of rigid fixa-
tion and bone grafting, complete
capsular release, ulnar neurolysis or
transposition, and initiation of early
motion.
Total Elbow Arthroplasty
Treating distal humeral nonunion
with total elbow arthroplasty has
been described by many authors.28,35,36
The surgical indications are a nonre-
constructable distal fragment and
the presence of posttraumatic ar-
throsis. Generally, this technique
should be reserved for elderly or less
active patients28 (Fig 6).
The early reports have not been
encouraging. Seven patients with
distal humeral nonunion 30 were
treated with semiconstrained total
elbow arthroplasty; two required
revision of loose humeral compo-
nents within 32 months of the initial
surgery. Another patient sustained
a radial nerve injury from extruded
cement and required tendon trans-
fers. Improvements in pain and
motion (average arc, 103°) in all pa-
tients were reported at final follow-
up.30 In 1989, Figgie et al36 reported
on 14 patients treated with semicon-
strained total elbow arthroplasty for
established distal humeral nonunion.
Seven postoperative complications
occurred in five patients; three had
surgical revision. Three patients
had wound-healing problems and
one had nerve palsy requiring revi-
sion surgery. Despite these compli-
cations, subjective improvement in
both pain and function was noted at
a mean follow-up of 5 years. A 100°
arc of motion was described for the
elbows that did not require revision
surgery. The authors emphasized
the need to maintain the epi-
condyles with their associated mus-
cle attachments to improve the sta-
bility of the elbow.
In 1995, Morrey and Adams 28
described their 8-year experience
using the Coonrad-Morrey semi-
constrained elbow replacement for
treatment of distal humeral non-
union. They reported results in 36
surviving patients (mean follow-
up, 50.4 months). Good or excel-
lent results were noted in 86% of
patients, with an average arc of
motion of 111°. Seven patients suf-
fered serious complications (requir-

A B C D

Figure 6 Anteroposterior (A) and lateral (B) radiographs of a distal humeral nonunion in a 72-year-old woman. Her deformities included
varus and severe malrotation (panel B), poor distal bone stock, and severe joint contracture—poor prognostic indicators for nonunion
repair. Postoperative anteroposterior (C) and lateral (D) radiographs of semiconstrained total elbow arthroplasty used for reconstruction.
The condyles and distal fragment are simply resected, creating a working space distally that facilitates elbow release and component
insertion without violating the triceps insertion. Rehabilitation was rapid, and the patient had a pain-free, stable, 120º arc of flexion-exten-
sion 6 months postoperatively.

Vol 11, No 1, January/February 2003 57

Management of Humeral Nonunion
ing revision surgery in five). There
were two deep infections, two
cases of particulate synovitis, one
case of worn bushings, and two
partial ulnar nerve palsies. The
authors recommended arthroplasty
as a treatment option in elderly
patients or those with nonrecon-
structable distal fragments. They
also recommended maintaining the
triceps insertion on the olecranon
and working through the space cre-
ated by excision of the distal humer-
al fragments. This allowed for easi-
er, quicker rehabilitation without
risk of detaching the extensor mech-
anism.
For total elbow replacement, the
patient is placed in a lateral decubi-
tus position, with bolsters or a bean
bag and an axillary roll under the
dependent arm. After inflation of
an upper arm tourniquet, a direct
posterior skin incision is made.
Skin flaps are elevated to expose the
medial and lateral extent of the tri-
ceps. The ulnar nerve is initially
identified, freed from scar tissue,
and protected (it is transposed ante-
riorly at the conclusion of the proce-
dure). The triceps is elevated off the
distal humerus, but its insertion in
References
1. Ward EF, Savoie FH III, Hughes JL Jr:
Fractures of the diaphyseal humerus,
in Browner BD, Jupiter JB, Levine AM,
Trafton PG (eds): Skeletal Trauma:
Fractures, Dislocations, Ligamentous
Injuries, ed 2. Philadelphia, PA: WB
Saunders, 1998, vol 2, pp 1523-1547.
2. Sarmiento A, Zagorski JB, Zych GA,
Latta LL, Capps CA: Functional brac-
ing for the treatment of fractures of the
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3. Farragos AF, Schemitsch EH, McKee
MD: Complications of intramedullary
nailing for fractures of the humeral
shaft: A review. J Orthop Trauma
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4. Schemitsch EH, Tencer AF, Henley MB:
Biomechanical evaluation of methods
of internal fixation of the distal
58
the olecranon is maintained. Any
retained hardware is removed. The
common flexor and extensor origins
are released from the epicondyles,
along with the collateral ligaments.
These tissues are reattached to the
fascia after component insertion.
The distal humeral fragments are
removed. The anterior capsule can
be elevated off the anterior humerus
to allow increased extension range.
By externally rotating the ulna, the
intramedullary canals of the hu-
merus or ulna can be accessed in
preparation for prosthesis implanta-
tion. After a trial reduction, the
semiconstrained humeral and ulnar
implants are cemented into position
and linked with a coupling bolt. If
hardware has been removed, it is
important to ensure that no methyl-
methacrylate extrudes through the
screw holes in the humerus or ulna
during implantation. After secure
wound closure, the patient is placed
in a padded Jones dressing in exten-
sion. On postoperative day 1, a
light dressing is placed on the arm
and early motion is begun. Night-
time extension splinting is used to
reduce the risk of developing a flex-
ion contracture.
humerus. J Orthop Trauma 1994;8:
468-475.
5. Otsuka NY, McKee MD, Liew A, et al:
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6. McKee M, Jupiter J, Toh CL, Wilson L,
Colton C, Karras KK: Reconstruction
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articular fractures of the distal humerus:
Methods and results in 13 adults. J Bone
Joint Surg Br 1994;76:614-621.
7. Neer CS II: Displaced proximal hu-
meral fractures. Part I: Classification
and evaluation. J Bone Joint Surg Am
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8. Neer CS II: Displaced proximal hu-
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Journal of the American Academy of Orthopaedic Surgeons
Summary
Successful treatment of humeral
nonunion can be achieved by apply-
ing strict principles of stable inter-
nal fixation with the liberal use of
autogenous bone graft. Fixed-angle
devices improve fixation and main-
tain correction of deformity in diffi-
cult proximal nonunions. Open re-
duction and plating is more reliable
than nailing for all diaphyseal non-
unions, including nonunion after
intramedullary nailing. In distal
humeral nonunion, careful attention
to the release of joint contractures,
combined with nerve releases
(when appropriate) and stable inter-
nal fixation with dual or triple plat-
ing, provides good functional
results in most cases. After surgical
treatment, surgeon-based, joint-spe-
cific outcome measures improve
markedly, although the patient’s
general health status may depend
more on comorbidity or compensa-
tion status. Arthroplasty of the
shoulder (for proximal nonunion)
or elbow (for distal nonunion) are
reasonable options in older, low-
demand patients if bony reconstruc-
tion is not feasible.
three-part and four-part displacement.
J Bone Joint Surg Am 1970;52:1090-1103.
9. Norris TR, Green A: Proximal hu-
merus fractures and fracture-disloca-
tions, in Browner BD, Jupiter JB, Levine
AM, Trafton PG (eds): Skeletal Trauma:
Fractures, Dislocations, Ligamentous
Injuries, ed 2. Philadelphia, PA: WB
Saunders, 1998, vol 2, pp 1570-1639.
10. Norris TR, Green A, McGuigan FX:
Late prosthetic shoulder arthroplasty
for displaced proximal humerus frac-
tures. J Shoulder Elbow Surg 1995;4:
271-280.
11. Craig EV: Open reduction and internal
fixation of greater tuberosity fractures,
malunions, and nonunions, in Craig EV
(ed): The Shoulder. Master Techniques
in Orthopaedic Surgery. New York,
NY: Raven, 1995, pp 289-307.

12. Ring D, McKee MD, Perey BH, Jupiter
JB: The use of a blade plate and autog-
enous cancellous bone graft in the
treatment of ununited fractures of the
proximal humerus. J Shoulder Elbow
Surg 2001;10:501-507.
13. Palmer SH, Handley R, Willett K: The
use of interlocked “customised” blade
plates in the treatment of metaphyseal
fractures in patients with poor bone
stock. Injury 2000;31:187-191.
14. Rosen H: The treatment of nonunions
and pseudarthroses of the humeral
shaft. Orthop Clin North Am 1990;21:
725-742.
15. Jupiter JB, von Deck M: Ununited hu-
meral diaphyses. J Shoulder Elbow Surg
1998;7:644-653.
16. Fears RL, Gleis GE, Seligson D: Diag-
nosis and treatment of complications,
in Browner BD, Jupiter JB, Levine AM,
Trafton PG (eds): Skeletal Trauma:
Fractures, Dislocations, Ligamentous
Injuries, ed 2. Philadelphia, PA: WB
Saunders, 1998, vol 1, pp 567-578.
17. Valchanou VD, Michailov P: High
energy shock waves in the treatment
of delayed and nonunion of fractures.
Int Orthop 1991;15:181-184.
18. Gill DR, Torchia ME: The spiral com-
pression plate for proximal humeral
shaft nonunion: A case report and
description of a new technique. J Orthop
Trauma 1999;13:141-144.
19. Patel VR, Menon DK, Pool RD, Simonis
RB: Nonunion of the humerus after
failure of surgical treatment: Manage-
ment using the Ilizarov circular fixator.
J Bone Joint Surg Br 2000;82:977-983.
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David M.W. Pugh, MD, FRCSC, and Michael D. McKee, MD, FRCSC
20. Lammens J, Bauduin G, Dreisen R, et
al: Treatment of nonunion of the
humerus using the Ilizarov external
fixator. Clin Orthop 1998;353:223-230.
21. Ackerman G, Jupiter JB: Non-union of
fractures of the distal end of the humerus.
J Bone Joint Surg Am 1988;70:75-83.
22. Jupiter JB: Complex non-union of the
humeral diaphysis: Treatment with a
medial approach, an anterior plate,
and a vascularized fibular graft. J Bone
Joint Surg Am 1990;72:701-707.
23. Wright TW, Miller GJ, Vander Griend
RA, Wheeler D, Dell PC: Reconstruc-
tion of the humerus with an intra-
medullary fibular graft: A clinical and
biomechanical study. J Bone Joint Surg
Br 1993;75:804-807.
24. Ring D, Jupiter JB, Quintero J, Sanders
RA, Marti RK: Atrophic ununited di-
aphyseal fractures of the humerus
with a bony defect: Treatment by
waveplate osteosynthesis. J Bone Joint
Surg Br 2000;82:867-871.
25. McKee MD, Miranda MA, Riemer BL,
et al: Management of humeral non-
union after the failure of locking intra-
medullary nails. J Orthop Trauma 1996;
10:492-499.
26. Robinson CM, Bell KM, Court-Brown
CM, McQueen MM: Locked nailing of
humeral shaft fractures: Experience in
Edinburgh over a two-year period.
J Bone Joint Surg Br 1992;74:558-562.
27. Constant CR, Murley AH: A clinical
method of functional assessment of
the shoulder. Clin Orthop 1987;214:
160-164.
28. Morrey BF, Adams RA: Semicon-
strained elbow replacement for distal
humeral nonunion. J Bone Joint Surg Br
1995;77:67-72.
29. Helfet DL, Schmeling GJ: Bicondylar
intraarticular fractures of the distal hu-
merus in adults. Clin Orthop 1993;292:
26-36.
30. Mitsunaga MM, Bryan RS, Linscheid
RL: Condylar nonunions of the elbow.
J Trauma 1982;22:787-791.
31. McKee MD, Jupiter JB, Bosse G,
Goodman L: Outcome of ulnar neu-
rolysis during post-traumatic recon-
struction of the elbow. J Bone Joint
Surg Br 1998;80:100-105.
32. Gallay SH, McKee MD: Operative
treatment of nonunions about the
elbow. Clin Orthop 2000;370:87-101.
33. Jupiter JB, Goodman LJ: The manage-
ment of complex distal humerus
nonunion in the elderly by elbow cap-
sulectomy, triple plating, and ulnar
nerve neurolysis. J Shoulder Elbow
Surg 1992;1:37-46.
34. Giannoudis PV, MacDonald DA,
Matthews SJ, Smith RM, Furlong AJ, De
Boer P: Nonunion of the femoral diaph-
ysis: The influence of reaming and non-
steroidal anti-inflammatory drugs.
J Bone Joint Surg Br 2000;82:655-658.
35. O’Driscoll SW: Prosthetic elbow
replacement for distal humeral frac-
tures and nonunions. Op Tech Orthop
1994;4:54-57.
36. Figgie MP, Inglis AE, Mow CS, Figgie
HE III: Salvage of non-union of supra-
condylar fracture of the humerus by
total elbow arthroplasty. J Bone Joint
Surg Am 1989;71:1058-1065.
59
Ordering and Interpreting Rheumatologic Laboratory Tests

Gregory C. Gardner, MD, and Nancy J. Kadel, MD

Abstract

Many mechanical and systemic conditions can cause joint pain and synovitis. increases with age, and to avoid
When rheumatologic illness is suspected, the initial evaluation begins with an unnecessary concern, it has been
accurate history, physical examination, and selective use of confirmatory test- suggested that age divided by 2 for
ing, which can help avoid common pitfalls inherent in serologic evaluation. men and age plus 10 divided by 2
Tests for erythrocyte sedimentation rate, C-reactive protein level, rheumatoid for women be used as the upper
factor, antinuclear antibodies, anticardiolipin antibodies and lupus anticoagu- limits of normal.3 Besides age, the
lant, HLA-B27, uric acid level, and Lyme disease, either alone or in combina- other important factor that elevates
tion, may support certain diagnoses. Using these tests nonselectively may yield the ESR is obesity.4 Adipose tissue
false-positive results, causing unnecessary concern and expense. However, is a source of interleukin-6 (IL-6),
using these tests effectively may reduce the number of unneeded invasive which increases liver production of
procedures. acute phase reactants, including fi-
J Am Acad Orthop Surg 2003;11:60-67 brinogen and C-reactive protein
(CRP).5
Although widely used, the ESR
has limited application as a diag-
Ordering and interpreting rheuma- method, the current accepted method nostic test, and it must always be
tologic laboratory tests for patients for performing the ESR, uses a 200- interpreted in a clinical context.
with inflammatory symptoms can mm vertically aligned column with a Sox and Liang2 have pointed out
be challenging. Having conceptual 2.5-mm diameter. The column is that, for patients with vague symp-
guidelines and indications to effec- filled with blood anticoagulated with toms who appear to be normal on
tively order serologic tests can help K3 EDTA.1 The distance that the col- examination, fewer than 6 in 10,000
to avoid unnecessary testing and umn of red blood cells settles within benefit from an ESR test. In addi-
potentially confusing results. The the plasma in 1 hour is reported in tion, a sample of patients from
tests should help confirm a clinical mm/h. Scandinavia with unexplained ele-
impression or sort out a differential The factors affecting the sedi- vation in the ESR followed over
diagnosis. Indiscriminate ordering mentation of red blood cells include
or asking for the “arthritis panel” the size of the cells, the viscosity of
should be avoided. Many rheuma- the plasma, and the repellent forces
tologic illnesses are relatively rare, between the negatively charged Dr. Gardner is Associate Professor, Division of
and because all tests have false- sialic acid molecules on the surface Rheumatology, and Adjunct Associate
positive rates, a positive result in a of each red blood cell (Fig. 1). The Professor, Department of Orthopaedic Surgery
patient with a low pretest probabil- presence of large or positively and Rehabilitation Medicine, University of
Washington School of Medicine, Seattle, WA.
ity of having the illness is likely a charged asymmetric proteins, espe-
Dr. Kadel is Assistant Professor, Department
false-positive. cially fibrinogen but also immuno- of Orthopaedic Surgery, University of
globulins, counteracts the repellent Washington School of Medicine.
force and allows the formation of
Acute Phase Reactants rouleaux, or coin-like rolls of cells, Reprint requests: Dr. Gardner, Division of
causing the cells to settle more Rheumatology, Box 356428, University of
Erythrocyte Sedimentation Rate rapidly than usual.2 Many factors Washington, Seattle, WA 98195.
The erythrocyte sedimentation influence the ESR (Table 1). The
rate (ESR) is a widely used, nonspe- range of normal in many laborato- Copyright 2003 by the American Academy of
cific, indirect measure of systemic ries is 0 to 15 mm/h for men and 0 Orthopaedic Surgeons.
inflammation. The Westergren to 20 mm/h for women. The ESR

60 Journal of the American Academy of Orthopaedic Surgeons


Normal level of fibrinogen Rouleau formation
with elevated level
of fibrinogen
Figure 1 Fibrinogen reduces red blood cell
repellent forces and increases the ESR.
- = sialic acid; + = fibrinogen.
time rarely developed any serious
illness.6 The following are general
guidelines:
(1) The ESR may take a few days
to a week to elevate and a similar
amount of time to regress once the
inflammatory stimulus is gone.
(2) An ESR is helpful to confirm
a clinical impression regarding the
presence or absence of inflammatory
disease, although occasionally pa-
tients with inflammatory diseases
present with a normal ESR. Age
and obesity elevate the ESR.
(3) Resolution of the ESR is a
useful marker of treatment success
in illnesses such as rheumatoid
arthritis, septic arthritis, and osteo-
myelitis.
(4) A very high ESR (>100
mm/h) almost always is associated
with underlying pathology.
C-Reactive Protein
First discovered in 1930 by Tillet
and Frances, CRP owes its name to
the ability of this liver-derived pro-
tein to precipitate pneumococcal C-
polysaccharide in the presence of
calcium.7 The liver produces CRP
under the influence of the inflam-
matory cytokines IL-1 and IL-6.
CRP levels begin to rise within 6
hours of an inflammatory stimulus,
peak in approximately 50 hours,8
and fall rapidly once the stimulus is
removed. CRP thus provides a
more immediate picture of the level
of inflammation than does the ESR,
Vol 11, No 1, January/February 2003
Gregory C. Gardner, MD, and Nancy J. Kadel, MD
in which the fibrinogen level rises
and falls more slowly9 (Fig. 2). Its
function in vivo is thought to be to
assist in the activation of the com-
plement system, influence phago-
cytic cell function, and augment
cell-mediated cytotoxicity to amplify
the immune response.8
The normal range of the CRP
level is 0 to 1 mg/dL. A level be-
tween 1 and 10 mg/dL is consid-
ered a moderate elevation and a
level above 10 mg/dL, a marked
elevation. Elevations are seen not
only in expected situations, such as
with infectious, inflammatory, and
malignant diseases, but also with
pregnancy and trauma. Factors
such as age, sex, anemia, and red
blood cell shape have little effect on
the CRP level, so there may be a
lower false-positive rate than occurs
with the ESR. The CRP level is a
direct measure of inflammation and
is as useful as the ESR in most situa-
tions. Since CRP is becoming easier
and cheaper to assess, it may some-
day supersede the ESR because it
more accurately reflects the current
level of inflammation.
Rheumatoid Factor
Rheumatoid factor (RF) as mea-
sured clinically is an IgM antibody
directed against the Fc portion of
Table 1
Factors That Influence the ESR
Elevate the ESR
Inflammatory diseases
(eg, rheumatoid arthritis, systemic
lupus erythematosus, osteomyelitis)
Increased globulin proteins
(eg, multiple myeloma)
Extensive tissue necrosis
(eg, myocardial infarction,
trauma, tumors)
Others: pregnancy, age, obesity,
heparinized blood
plasma concentration
Relative change in
C-reactive protein
Fibrinogen (ESR)
7 14 21
Inflammatory event Days
Figure 2 Comparison of time course of the
ESR and CRP level after a single inflamma-
tory stimulus. (Adapted with permission
from Barland P, Lipstein E: Selection and
use of laboratory tests in the rheumatic dis-
eases. Am J Med 1996;100[suppl 2A]:16S-23S.)
the patient’s own IgG (Fig. 3). Why
the body makes RF is uncertain,
although it may be to help clear
immune complexes by stabilizing
low-affinity IgG-antigen interac-
tions and improving opsonization
by fixing complement more effi-
ciently than would occur without
RF. 10 RF is commonly secreted
during acute infections and proba-
bly is part of the normal immune
response. Other isotypes of RF can
be produced (IgG, IgA) but cur-
rently are not measured clinically.
However, IgA RF may prove to be
useful clinically because it has been
Lower the ESR
Increased plasma viscosity
(eg, cold agglutinin disease)
Abnormal red cell shape
(eg, sickle cell disease)
Decreased plasma proteins
(eg, hepatic necrosis, cachexia)
Other: trichinosis
61
Ordering and Interpreting Rheumatologic Laboratory Tests
IgM rheumatoid factor
IgG
Figure 3 Rheumatoid factor is an IgM anti-
body directed against the Fc region of IgG.
shown to help predict a more severe
disease course.11
Latex agglutination testing, usu-
ally done by hand, is widely used to
measure RF, although it is being
supplanted by other methods.
Enzyme-linked immunosorbent
assay (ELISA) and nephelometry
are capable of being automated and
are more sensitive than the latex
method.11 The latex test is reported
in a titer, that is, serial dilution of
serum, which is a discontinuous
measurement and has an accuracy
of ±1 dilution. Most clinical labora-
tories consider a dilution >1:40 to be
positive. Nephelometry is able to
quantitate antigen-antibody interac-
tion by measuring laser light scatter
caused by the formation of immune
complexes. The nephelometry test
is usually reported in international
units (IU); the normal range de-
pends on the specific laboratory but
usually is <20 IU.
When RF testing is ordered indis-
criminately, the false-positive rate
can be quite high. In one study,
only 86 of 563 RF tests ordered dur-
ing a 6-month period were positive,
and only 21 of the 86 patients actu-
ally had rheumatoid arthritis. 12
Thus, three quarters of positive re-
sults were false-positive for the
diagnosis of rheumatoid arthritis. A
number of critical points should be
kept in mind when ordering RF
tests:
(1) RF is present in 70% to 90% of
patients with rheumatoid arthritis;
62
therefore, a negative RF result does
not rule out rheumatoid arthritis.11
(2) RF may take several months
to appear in the serum after arthritis
develops.
(3) The level of RF is prognostic,
that is, the higher the level, the
worse the prognosis.
(4) An elevated RF level is not
specific for rheumatoid arthritis and
can be found in a variety of other
illnesses, including other rheuma-
tologic diseases (eg, lupus eryth-
ematosus, Sjögren’s syndrome,
myositis, and cryoglobulinemia) as
well as infectious diseases (eg,
endocarditis, tuberculosis, syphilis,
and hepatitis C). An elevated RF
level also is associated with aging,
idiopathic pulmonary fibrosis, cir-
rhosis, and sarcoidosis. This fact is
particularly important because dis-
eases like hepatitis C can present
with rheumatoid-like synovitis and
a positive RF test result.
Antinuclear Antibodies
Diagnostic testing for systemic
lupus erythematosus (SLE) began
in 1948 with the description of the
lupus erythematosus cell, a poly-
morphonuclear neutrophil that had
engulfed a cell nucleus. The lupus
erythematosus cell test is now of
historical significance and is no
longer available at most immunolo-
gy laboratories. In 1957, Friou
described the fluorescent antinu-
clear antibody (FANA) test, which
marked a new era in the diagnostic
testing of SLE.13 Over time, subsets
of antinuclear antibodies (ANAs)
have been used to classify various
autoimmune syndromes.
ANA testing is done in two se-
quential steps. The first is testing
for the presence of a FANA; the sec-
ond, if the FANA test is positive, is
testing for specific autoantibodies
that help to classify the potential
underlying connective tissue dis-
ease.13,14 The FANA test is done by
placing patient sera over a thin layer
of cells from a HEp-2 cell line (a line
Journal of the American Academy of Orthopaedic Surgeons
Antinuclear
antibody
Nucleus
HEp-2 cells
Slide
Antihuman IgG
Fluorescein-labeled
antihuman antibody
Figure 4 FANA test technique. Step 1
(top): Patient serum containing ANAs is
placed on a slide containing HEp-2 cells.
The ANAs attach to the cell nucleus. Step
2 (bottom): The preparation is washed, and
fluorescein-labeled antihuman IgG is
added. If RF is present, the preparation
glows under the fluorescence microscope.
of human epithelioma cells) (Fig. 4).
ANAs attach to the specific nuclear
antigen in the cell nucleus and will
not wash away. An antihuman IgG
conjugated to a fluorochrome tag is
then added to the cells, and the cells
are viewed under a microscope
with ultraviolet light excitation.
Common patterns include speckled,
rim, homogeneous, centromere, and
nucleolar, reflecting the types of
antigens present, which have a
loose association with specific syn-
dromes (Table 2).13 If the FANA
test is positive, a more specific test,
such as an ELISA, can be done to
detect specific antinuclear antigens.
The ELISA results help to classify
the autoimmune disorder. Most
laboratories report a FANA titer of
1:40 to 1:80 as positive, although
patients with an active autoimmune
disorder rarely have such low titers.
Most rheumatologists view titers
≥1:160 as significant. The most
helpful result on the FANA test is a
negative one. A positive test does
not mean the patient has an autoim-
mune condition but indicates that
clinical correlation is needed. The
following points may be useful
 Gregory C. Gardner, MD, and Nancy J. Kadel, MD

Table 2
Autoantibody Profiles in Rheumatic Diseases

Drug-Induced
Condition Systemic Lupus Systemic Lupus Sjögren’s Mixed Connective
Autoantibody Erythematosus Erythematosus Syndrome Tissue Disease Scleroderma

ANA pattern Homogeneous, Speckled Speckled Speckled Nucleolar (diffuse),

rim, speckled centromere (crest)
Anti-dsDNA 60% Rare Absent Absent Absent
Anti-Sm 20% Absent Absent Absent Absent
Anti-SSA 30% Absent 70% Rare Rare
Anti-SSB 15% Absent 35% Rare Rare
Anti-RNP 30% Absent Absent 95% Rare
Antihistone 30% - 50% 95% Absent Absent 10% - 25% (diffuse)
Anti–Scl-70 Absent Absent Absent Absent 25% - 30% (diffuse)
Rheumatoid factor 15% - 35% Rare 50% - 75% 25% - 50% Rare

ANA = antinuclear antibody; dsDNA = double-stranded DNA; Sm = Smith; SSA/SSB = Sjögren’s syndrome A/B; RNP = ribonucleo-
protein; Scl = scleroderma

when interpreting ANA test re-
sults:
(1) Ninety-five percent of pa-
tients with SLE have a positive
FANA test result; the remaining 5%
have a negative FANA test result
but a positive result for antibodies
to SS-A (Sjögren’s syndrome A, also
known as antibodies to Ro). Thus,
negative FANA and negative SS-A
test results rule out SLE.
(2) A positive FANA test result
does not mean a disease is present.
Low titers (eg, 1:40, 1:80) in patients
without objective abnormalities
(aches and pains, fatigue) are likely
false positive.15
(3) A diagnosis of SLE is made
on the basis of a positive FANA test
result at a reasonable titer and the
presence of three other objective cri-
teria for SLE, such as swollen joints,
nephritis, or pericarditis (not aches
and pains or reports of a rash in the
distant past).
(4) Other diseases can cause a
positive FANA test result, notably
diseases of the thyroid, such as
Graves’ disease or Hashimoto’s thy-
roiditis. The false-positive rate in-
creases with age, as do false-positive
rates for many other autoantibodies.
Several specific patterns of auto-
antibodies are useful to remember:
(1) A centromere pattern on the
FANA test indicates CREST syn-
drome (calcinosis, Raynaud’s phe-
nomenon, esophageal problems,
sclerodactyly, telangiectasias).
(2) Antibodies to dsDNA (double-
stranded DNA) or Sm (Smith) are
seen in SLE.
(3) Antibodies to Scl-70 are seen
in a minority of persons with
scleroderma but predict severe dis-
ease.
(4) Antibodies to histone are seen
primarily in persons with drug-
induced SLE.
(5) High levels of antibodies to
ribonucleoprotein are seen in mixed
connective tissue disease, a condi-
tion that has features of scleroderma
and SLE.
Anticardiolipin Antibodies and
Lupus Anticoagulant
These tests are used to evaluate
patients with hypercoagulable
states. Anticardiolipin (or antiphos-
pholipid) antibodies are a heteroge-
neous family of antibodies that are
directed against components of the
coagulation pathway. Their pres-
ence may put patients at risk of
thrombosis. The same is true of the
lupus anticoagulant antibodies,
which prolong the partial thrombo-
plastin time and also may lead to
thrombosis.
These two kinds of antibodies
can be present in up to 40% of
patients with SLE or can occur in
isolation, leading to primary anti-
phospholipid syndrome. Clinical
manifestations of these antibodies
include recurrent fetal loss in the
second trimester, venous and arte-
rial thrombosis, and thrombocyto-
penia.16 Other possible manifesta-
tions include transverse myelopathy,
cardiac valvular disease, and osteo-
necrosis. Three points should be
kept in mind when considering
whether testing will be useful:
(1) Anticardiolipin antibodies
and lupus anticoagulant are not
diagnostic tests for SLE or other con-
nective tissue diseases.
(2) If hypercoagulability is a con-
cern, testing should be done for both
lupus anticoagulant and anticardio-
lipin antibodies because a patient
may have one or both. These tests
are only part of an evaluation for a
hypercoagulable state.

Vol 11, No 1, January/February 2003 63

Ordering and Interpreting Rheumatologic Laboratory Tests
(3) These tests should be ordered
only when hypercoagulability is
strongly suspected. Like all other
such tests, they have a relatively
constant false-positive rate and
could lead to unwarranted concern
and expensive follow-up tests.
Human Leukocyte Antigen–B27
The human leukocyte antigen
(HLA) molecules are part of the
major histocompatibility complex
encoded by genes on the short arm
of chromosome 6. These molecules
are important in self-recognition and
immune response. HLA-B27 is one
of the class I antigens that are found
on all cells except red blood cells
and are important for cell-mediated
immunity. Certain HLA molecules
have been found to indicate risk of
various diseases. The HLA-B27
antigen indicates a risk of spondy-
loarthropathies.17 This antigen is
found in approximately 8% of
European-Americans and 4% of
African-Americans. The test has a
92% sensitivity and specificity for
ankylosing spondylitis in European-
Americans and is present in >90% of
affected individuals. The test also is
useful for diagnosing Reiter’s syn-
drome because 80% of these patients
carry the antigen.
The diagnosis of ankylosing
spondylitis depends on the history,
examination, and typical radio-
graphic findings of sacroiliitis.
When the history and examination
are highly suggestive but there is no
radiographic evidence of the disease
(either on plain radiographs or com-
puted tomography [CT]), HLA-B27
may be helpful in decision-making.
In these borderline situations, a posi-
tive test makes the likelihood of the
disease approximately equal to the
specificity (ie, about a 92% chance of
having ankylosing spondylitis),
whereas a negative test makes the
likelihood of not having the disease
approximately equal to the sensi-
tivity (ie, about a 92% chance of not
having ankylosing spondylitis).16
64
Generally, an HLA-B27 test
should be ordered only when the
patient’s history is compatible with
ankylosing spondylitis or Reiter’s
syndrome and definitive radio-
graphic changes are lacking, or, in
the case of Reiter’s syndrome, when
clinical features are insufficient to
make a definitive diagnosis. The
test should not be ordered when the
history clearly is that of mechanical
low back pain because <20% of
HLA-B27–positive patients have
associated clinical manifestations.
Uric Acid
Prolonged hyperuricemia fre-
quently leads to the clinical symp-
toms of gout. In patients with ar-
thritis consistent with gout, demon-
strating the presence of intracellular
crystals is key to the diagnosis.
Serum uric acid levels may be ele-
vated during an acute attack of gout,
but in some patients, the levels may
decrease 1 to 2 mg/dL or more
while inflammation is present.
Thus, in a patient with gout with a
preattack serum uric acid level of 7
to 9 mg/dL, that elevated level may
fall into the normal range during an
acute attack.18 This is particularly
true in alcoholics.19 Uric acid levels
are best checked once the attack has
subsided. Demonstrating uric acid
crystals from a joint aspiration is not
necessary with each attack but
should be done at least once to aid
decision-making.
The diagnosis of gout sometimes
is assigned incorrectly, especially to
patients with joint pain and asymp-
tomatic hyperuricemia but without a
convincing history of gout.20 There-
fore, the diagnosis rests on visualiz-
ing urate crystals in white blood
cells taken from the inflamed joint,
not simply on the presence of hyper-
uricemia. Only a small amount of
fluid (a drop or less) is necessary to
make the diagnosis. Because gout
can mimic septic arthritis, aggressive
therapy for infection should be avoid-
ed before gout has been ruled out.
Journal of the American Academy of Orthopaedic Surgeons
Lyme Disease
Lyme arthritis is a late manifes-
tation of infection with the tick-
borne organism Borrelia burgdorferi.
The disease most commonly occurs
in the spring and summer in the
northeast and upper midwest of
the United States. 21 Arthritis
occurs either as an intermittent,
migratory polyarthritis in half of
the patients who develop late-stage
disease or as a chronic monoarthri-
tis, usually affecting the knee with
large, inflammatory effusions.
The diagnosis should be made on
clinical grounds (the season, regional
location, and pattern of the rash—
erythema chronicum migrans).
Positive serologic testing increases
the posttest probability of Lyme dis-
ease and helps in deciding on anti-
biotic therapy. Testing detects the
presence of antibodies to the causa-
tive organism, not the organism
itself, so those who may have been
infected but have cleared the organ-
ism still would test positive but may
not have active disease. In addition,
the test has a 5% false-positive rate,
and false-positive results are com-
mon among persons with other
forms of arthritis, such as rheuma-
toid arthritis and SLE. The initial
test is an ELISA; if it is positive, it is
followed by a confirmatory Western
blot analysis. In addition, poly-
merase chain reaction (PCR) testing
can detect B burgdorferi DNA within
the joint fluid of patients suspected to
have Lyme arthritis.21 This test has
a high specificity and sensitivity for
the organism and may be useful in
distinguishing patients with active
B burgdorferi infections from those
who are simply seropositive and
have other causes of arthritis. Pa-
tients with late Lyme disease (ie,
those with arthritis) almost always
are seropositive, so a negative test
virtually rules out Lyme arthritis.
Lyme serology should be ordered
only when the clinical diagnosis is
highly suggestive. Using this test
for evaluating patients with a low

probability of infection can lead to
incorrect diagnosis and overtreat-
ment. In high-risk areas, a certain
percentage of the population will be
antibody-positive but disease-nega-
tive, so clinical correlation is partic-
ularly important. In this situation,
PCR for B burgdorferi in the joint
fluid may be useful.
Clinical Scenarios
Carpal Tunnel Syndrome and
Stiff Joints
A 26-year-old woman was re-
ferred for evaluation and treatment
of carpal tunnel syndrome. She
reported paresthesias in both hands,
especially the right, that awakened
her from sleep and also were pres-
ent while driving. She also reported
stiffness of 2 months’ duration in
the hands and wrists that was
worse in the morning than during
the day.
The physical examination dis-
closed swelling and tenderness of
the metacarpophalangeal, proximal
interphalangeal, metatarsopha-
langeal, and wrist joints. She had
positive Tinel’s and Phalen’s signs,
greater on the right than left. Other-
wise, the examination was normal.
Laboratory testing included a nor-
mal complete blood count, an ESR
of 42 mm/h, a FANA titer of 1:40,
and negative results for SS-A and
hepatitis C antibodies. RF was ele-
vated at 215 IU.
She was given neutral wrist
splints and referred with the diagno-
sis of RA to a rheumatologist. She
was given methotrexate and low-
dose prednisone. In spite of this
therapy, she required endoscopic
carpal tunnel release on the right to
relieve symptoms. Her rheumatoid
arthritis currently is well controlled
by methotrexate 15 mg/week and
prednisone 2.5 mg/day.
This patient presented with an
inflammatory polyarthritis affecting
small joints of the hands and feet,
Vol 11, No 1, January/February 2003
Gregory C. Gardner, MD, and Nancy J. Kadel, MD
with carpal tunnel syndrome as a
result of underlying synovitis. The
initial differential diagnosis included
RA, lupus, and hepatitis C infection.
A diagnosis of RA was made on the
basis of clinical and laboratory data.
Typically, a FANA titer of 1:40 is
not clinically meaningful.
Low Back Pain With a Sore Heel
A 25-year-old man was referred
for persistent right Achilles tendini-
tis. The tendinitis had appeared 2
months earlier and possibly began
after a game of soccer. He had tried
nonsteroidal anti-inflammatory
drugs (NSAIDs), rest, and a heel lift,
all without benefit.
On physical examination, he had
trouble removing his socks because
of back stiffness. There was tender-
ness to palpation of the sacroiliac
joints bilaterally and also low back
pain on both sides with Patrick’s
test. Lumbar range of motion was
normal. There was also tenderness
and swelling of the right Achilles
tendon at the insertion into the cal-
caneus. A plain radiograph, pelvic
outlet view, demonstrated sacroili-
itis consistent with ankylosing
spondylitis. His ESR was elevated
at 45 mm/h. He was referred to a
rheumatologist and given high-dose
NSAIDs and sulfasalazine; the symp-
toms resolved.
Insertional Achilles tendinitis
is often caused by a spondylo-
arthropathy. This, together with
back stiffness, suggests ankylosing
spondylitis. If the radiograph of the
sacroiliac joints had been negative or
equivocal, CT of the sacroiliac joints
could have been done. If this were
negative, an HLA-B27 test could
have been considered. Testing for
RA and SLE was not needed
because Achilles tendinitis is unusu-
al in these diseases.
Arthralgias and Fatigue
A 36-year-old woman reported
bilateral hand pain and numbness.
She was referred for possible carpal
tunnel syndrome. She had devel-
oped the pain in the hands several
years earlier and had recently quit
her job as a secretary because of her
symptoms. She also reported fa-
tigue and diffuse muscle aches.
The physical examination was
remarkable for tenderness without
swelling of multiple metacar-
pophalangeal, proximal interpha-
langeal, and distal interphalangeal
joints of both hands, with grimac-
ing. She had tenderness around
various joints and muscles to the
pressure of the examination, with-
out evidence of swelling. Neuro-
logic examination was unremark-
able except for Tinel’s sign at the
right wrist, which produced pain
into all of the fingers. Review of
previous laboratory tests for her
complaints demonstrated a normal
complete blood count, chemistry
panel, ESR, and thyroid-stimulat-
ing hormone, calcium, and creatine
kinase levels. Electrodiagnostic
study results were normal. She
was referred to a rheumatologist.
A diagnosis of fibromyalgia was
made, and she was prescribed low-
dose nortriptyline and an exercise
program.
Her presentation is not unusual
for fibromyalgia. RF, FANA, and SS-
A tests should be avoided in such sit-
uations because they confuse the
issue. Many patients with fibromy-
algia have been told that they have
SLE, based on a false-positive FANA
test result.
Bilateral Shoulder Pain
A 66-year-old woman was
referred to an orthopaedic clinic for
persistent rotator cuff tendinitis.
The symptoms had begun 4 months
earlier. She had stiffness and aching
in both shoulders with overhead
activities. Morning stiffness in the
shoulders and hips required her to
roll out of bed. She had completed
two courses of physical therapy for
the shoulder, without much benefit.
After her latest physical therapy
65
Ordering and Interpreting Rheumatologic Laboratory Tests
course, her primary care physician
had given her a corticosteroid injec-
tion in the right shoulder, which
improved her general stiffness and
pain for 4 days, although both then
returned.
The physical examination
revealed signs of rotator cuff ten-
dinitis bilaterally. The rest of the
examination was normal; in partic-
ular, there was no evidence of sy-
novitis of the small joints of the
hands or feet. Laboratory tests
demonstrated a hematocrit level
of 33%, normal chemistry panel,
and ESR of 80 mm/h. A suspected
diagnosis of polymyalgia rheumatica
was confirmed by a rheumatology
consultant. Low-dose prednisone
was started, and her symptoms
resolved dramatically within 24
hours.
The distribution of symptoms and
signs suggests the diagnosis of
polymyalgia rheumatica. RF and
FANA tests are not needed unless
there is joint swelling or other objec-
tive abnormalities. The arthritis/
periarthritis typical of polymyalgia
often can cause rotator cuff signs
and symptoms. In any older person
with bilateral shoulder symptoms,
polymyalgia rheumatica should be
considered in the differential diag-
nosis.
Swollen Knee and
Inflammatory Fluid
A 55-year-old man reported
swelling of 1 month’s duration in the
left knee. His history was negative
for trauma or previous problems
with the knee. He had stiffness in
the morning, with some improve-
ment during activity.
The physical examination revealed
a moderate-sized effusion of the
knee. There was diffuse swelling of
the left second toe and a patch of
psoriasis on his scalp. Aspiration of
the joint yielded 40 mL of cloudy
fluid with a white blood cell count
of 30,000/µL, mostly neutrophils.
Laboratory tests demonstrated a
66
normal complete blood count and
an ESR of 35 mm/h.
The diagnosis of psoriatic arthri-
tis was considered; he was pre-
scribed NSAIDs and referred to a
rheumatologist, who prescribed
methotrexate. There was moderate
improvement of the joints and skin.
Etanercept was added, with notable
improvement.
This patient had an inflammatory
form of arthritis confirmed by the
fluid in the knee. Checking the syno-
vial fluid cell count at the knee may
help avoid arthroscopy. The presen-
tation in this case is typical of psori-
atic arthritis, and there is no need for
FANA or RF tests. A follow-up ESR
or CRP test is reasonable as a marker
of treatment success. Psoriatic ar-
thritis is not associated with HLA-
B27, and testing would not be use-
ful in this situation. In an endemic
area, Lyme serology is not unrea-
sonable when only the knee is
affected.
Bilateral Heel Pain
A 24-year-old soccer player
reported bilateral heel pain of 6
months’ duration that was worse in
the morning and partially improved
with activity. He had tried NSAIDs
(with some benefit), over-the-
counter orthotics, and even a poste-
rior night splint, without a notable
change in symptoms. He also re-
ported occasional low back stiffness
that he ascribed to his soccer play.
He was diagnosed with bilateral
plantar fasciitis and referred for
other therapeutic options.
Examination demonstrated evi-
dence of bilateral plantar fasciitis
and was otherwise negative. Plain
radiographs, including a pelvic
outlet view of the sacroiliac joints
and views of the feet, were unre-
markable. The CRP level was ele-
vated at 2.8 mg/dL, and results of
subsequent CT of the sacroiliac
joints were negative. HLA-B27
antigen was then checked and was
positive.
Journal of the American Academy of Orthopaedic Surgeons
He was referred to a rheumatolo-
gist and begun on indomethacin
and sulfasalazine, with excellent re-
sponse. His subsequent course was
marked by intermittent bouts of iri-
tis, and 2 years later, radiography
revealed that he had developed
sacroiliitis.
An HLA-B27 determination is
useful in this situation, that is, neg-
ative radiographic results but posi-
tive symptoms and an elevated
CRP level. HLA-B27 antigen test-
ing was helpful because of the
impression that the patient had an
inflammatory form of enthesopa-
thy. The HLA-B27 test also aided
in treatment decisions. The CRP
level was useful to confirm the
inflammatory nature of the symp-
toms, but it would not have ruled
out an inflammatory cause if the
level had been normal.
Knee Swelling
A 45-year-old forest ranger who
worked in Minnesota was referred
for persistent right knee swelling.
He was known to be antibody posi-
tive for B burgdorferi. One year ear-
lier, his right knee had swelled,
with the synovial fluid showing
25,000 white blood cells/µL, most-
ly neutrophils. He had been treat-
ed with 60 days of doxycycline
without change in the swelling.
Before treatment with doxycycline,
PCR results of the synovial fluid
were positive for B burgdorferi. He
was sent for arthroscopic biopsy to
rule out granulomatous disease and
to obtain synovium for B burgdorferi
culture.
The physical examination re-
vealed only the swollen right knee.
A repeat synovial PCR for B burg-
dorferi was negative, and the patient
was thought to have post-Lyme
inflammatory arthritis. A right knee
synovectomy was done, and he was
given hydroxychloroquine, which
controlled his synovitis.
This is a case in which persistent
synovitis developed after Lyme

arthritis. Many such patients carry
the HLA-DR4 gene and require
treatment with disease-modifying
antirheumatic drugs, such as hy-
droxychloroquine, as well as re-
duction of the synovial mass by
arthroscopic synovectomy. With-
out such treatment, some patients
develop erosive arthritis.
References
1. International Committee for Standard-
ization in Haematology. Recommen-
dation of measurement of erythrocyte
sedimentation rate of human blood.
Am J Clin Pathol 1977;68:505-507.
2. Sox HC Jr, Liang MH: The erythrocyte
sedimentation rate: Guidelines for rational
use. Ann Intern Med 1986;104:515-523.
3. Miller A, Green M, Robinson D:
Simple rule for calculating normal
erythrocyte sedimentation rate. Br
Med J (Clin Res Ed) 1983;286:266.
4. Leff RD, Akre SP: Letter: Obesity and
the erythrocyte sedimentation rate.
Ann Intern Med 1986;105:143.
5. Yudkin JS, Stehouwer CD, Emeis JJ,
Coppack SW: C-reactive protein in
healthy subjects: Associations with obe-
sity, insulin resistance, and endothelial
dysfunction: A potential role for
cytokines originating from adipose tis-
sue? Arterioscler Thromb Vasc Biol
1999;19:972-978.
6. Rafnsson V, Bengtsson C, Lennartsson
J, Lindquist O, Noppa H, Tibblin E:
Erythrocyte sedimentation rate in a
population sample of women with spe-
cial reference to its clinical and prog-
nostic significance. Acta Med Scand
1979;206:207-214.
7. Foglar C, Lindsey RW: C-reactive
protein in orthopedics. Orthopedics
1998;21:687-691.
Vol 11, No 1, January/February 2003
Gregory C. Gardner, MD, and Nancy J. Kadel, MD
Summary
Understanding the basic principles
of tests for inflammatory joint disor-
ders can help the clinician distin-
guish various forms of synovitis.
Testing should be ordered only after
a thorough history and physical
examination. The selection of tests
8. Young B, Gleeson M, Cripps AW: C-
reactive protein: A critical review.
Pathology 1991;23:118-124.
9. Barland P, Lipstein E: Selection and
use of laboratory tests in the rheumatic
diseases. Am J Med 1996;100(suppl
2A):16S-23S.
10. Tighe H, Carson DA: Rheumatoid fac-
tor, in Ruddy S, Harris ED Jr, Sledge
CB, Budd RC, Sergent JS (eds): Kelley’s
Textbook of Rheumatology, ed 6. Phila-
delphia, PA: WB Saunders, 2001, pp
151-160.
11. Jonsson T, Steinsson K, Jonsson H,
Geirsson AJ, Thorsteinsson J, Valdi-
marsson H: Combined elevation of
IgM and IgA rheumatoid factor has
high diagnostic specificity for rheuma-
toid arthritis. Rheumatol Int 1998;18:
119-122.
12. Shmerling RH, Delbanco TL: How
useful is the rheumatoid factor? An
analysis of sensitivity, specificity, and
predictive value. Arch Intern Med
1992;152:2417-2420.
13. Peng SL, Craft J: Antinuclear antibod-
ies, in Ruddy S, Harris ED Jr, Sledge
CB, Budd RC, Sergent JS (eds): Kelley’s
Textbook of Rheumatology, ed 6. Phila-
delphia, PA: WB Saunders, 2001, pp
161-174.
14. Shmerling RH, Liang MH: Laboratory
assessment, in Klippel JH, Weyand
should be specific to help clarify a
borderline clinical scenario.
Nonselective use of testing may
lead to false-positive results, which
can cause unnecessary concern and
increased expense.
Acknowledgment: We wish to thank Mart
Mannik, MD, for his thoughtful review and
useful suggestions.
CM, Wortmann RL (eds): Primer on
the Rheumatic Diseases, ed 11. Atlanta,
GA: Arthritis Foundation, 1997, pp
94-97.
15. Slater CA, Davis RB, Shmerling RH:
Antinuclear antibody testing: A study
of clinical utility. Arch Intern Med
1996;156:1421-1425.
16. Harris EN: Antiphospholipid syn-
drome, in Klippel JH, Weyand CM,
Wortmann RL (eds): Primer on the
Rheumatic Diseases, ed 11. Atlanta, GA:
Arthritis Foundation, 1997, pp 313-315.
17. Khan MA: Clinical features of anky-
losing spondylitis, in Klippel JH,
Dieppe PA (eds): Practical Rheuma-
tology. London, UK: Times Mirror
International Publishers Limited, 1995,
pp 211-220.
18. Hadler NM, Franck WA, Bress NM,
Robinson DR: Acute polyarticular
gout. Am J Med 1974;56:715-719.
19. Vandenberg MK, Moxley G, Breitbach
SA, Roberts WN: Gout attacks in
chronic alcoholics occur at lower serum
urate levels than in non-alcoholics.
J Rheumatol 1994;21:700-704.
20. Wolfe F, Cathey MA: The misdiagnosis
of gout and hyperuricemia. J Rheumatol
1991;18:1232-1234.
21. Steere AC: Diagnosis and treatment of
Lyme arthritis. Med Clin North Am
1997;81:179-194.
67
 Longitudinal Radioulnar Dissociation

Tamara D. Rozental, MD, Pedro K. Beredjiklian, MD, and David J. Bozentka, MD

Abstract

Proximal translation of the radius is a complication of radial head fractures that the most force was transmitted from
occurs in association with disruption of the longitudinal soft-tissue stabilizers the wrist to the radial head with the
of the forearm. The sequelae of this process include debilitating wrist and elbow elbow in extension and the forearm
pain secondary to ulnocarpal and radiocapitellar abutment as well as loss of in pronation.
grip strength. When radioulnar dissociation is recognized early, treatment The primary restraint to proxi-
involves prevention of proximal radial migration by preservation of the radial mal migration of the radius is the
head and stabilization of the distal radioulnar joint. When primary bony repair intact radial head abutting the
of the radial head is not feasible, prosthetic replacement of the radial head is nec- capitellum.6-8 Soft-tissue structures
essary to prevent proximal radial migration. Management is complex in chron- that provide additional forearm lon-
ic cases in which longitudinal radioulnar dissociation is diagnosed after radial gitudinal stability include the inter-
migration has occurred. Treatment goals include normalization of the radioul- osseous membrane of the forearm,
nar relationship and prevention of further migration. Although several recon- the triangular fibrocartilage, and the
structive treatment options are available, no clear solutions exist, and long-term ligaments of the distal radioulnar
prognosis is guarded. Therefore, early recognition of longitudinal forearm joint (volar and dorsal radioulnar
instability is critically important. ligaments). With injury or excision
J Am Acad Orthop Surg 2003;11:68-73 of the radial head, normal load shar-
ing at the radiocapitellar joint no
longer can occur and all compres-
sive load is transferred from the dis-
Forceful loading of the forearm and the biomechanics of radioulnar dis- tal radius to the ulna through the
elbow during a fall on an out- sociation has led to the develop- interosseous membrane and distal
stretched hand can lead to fracture ment of a schema for diagnosis and radioulnar joint.9 The surrounding
of the radial head with concomitant treatment. soft tissues thus act as secondary
injury to stabilizing ligamentous restraints to proximal radial migra-
structures. Proximal translation of tion. Longitudinal radioulnar disso-
the radius occurs when a radial Pathoanatomy and
head fracture happens in associa- Biomechanics
tion with disruption of the longitu-
dinal stabilizers of the forearm. The Load is transmitted from the wrist Dr. Rozental is Resident, Department of Or-
clinical presentation ranges from to the humerus during grip and lift- thopaedic Surgery, Hospital of the University
acute disruption of the distal radio- ing activities. Studies of load shar- of Pennsylvania, Philadelphia, PA. Dr.
Beredjiklian is Assistant Professor, Department
ulnar joint to insidious ulnocarpal ing in the forearm show that the
of Orthopaedic Surgery, University of Pennsyl-
impingement with worsening pain radius bears most (about 80%)3 of vania School of Medicine. Dr. Bozentka is As-
and loss of motion. the load at the wrist but that the sociate Professor, Department of Orthopaedic
Curr and Coe 1 first reported a load-sharing ratio equalizes toward Surgery, University of Pennsylvania School of
fracture-dislocation of the radial the elbow. Halls and Travill4 re- Medicine, Philadelphia.
head with dorsal dislocation of the ported that the radiocapitellar joint
Reprint requests: Dr. Beredjiklian, One Cupp
distal ulna. Essex-Lopresti2 later bears 57% of the load in the proximal
Pavilion, 39th and Market Streets, Philadelphia,
described two cases of acute radial forearm and the ulnohumeral ar- PA 19104.
head fractures with disruption of the ticulation bears 43%. Subsequently,
distal radioulnar joint, and his name Morrey et al 5 studied changes in Copyright 2003 by the American Academy of
has been given to these uncommon force transmission with variations Orthopaedic Surgeons.
injuries. Subsequent knowledge of in forearm rotation and found that

68 Journal of the American Academy of Orthopaedic Surgeons


ciation can ensue if a radial head
fracture occurs in association with
damage to any of these stabilizing
soft-tissue structures (Fig. 1).
The interosseous membrane of the
forearm, which consists of fibrous
tissue running obliquely from the
radius to the ulna, transfers load
from the radius to the ulna. The in-
terosseous membrane plays an im-
portant role in load sharing; section-
ing of the interosseous membrane
prevents force transmission from the
distal radius to the ulnohumeral
articulation. 10 The existence of a
central band of collagenous tissue
approximately twice the thickness of
the remaining membrane is a con-
stant finding in cadaveric studies.7
Radial migration
Interosseous
membrane rupture
Displaced radial
head fracture
Figure 1 Longitudinal radioulnar dissoci-
ation with proximal radial migration
caused by a comminuted radial head frac-
ture and damage to the interosseous mem-
brane. (Adapted with permission from
Edwards GS Jr, Jupiter JB: Radial head
fractures with acute distal radioulnar dis-
sociation: Essex-Lopresti revisited. Clin
Orthop 1988;234:61-69.)
Vol 11, No 1, January/February 2003
This central band, also called the
interosseous ligament of the fore-
arm, is consistently located at a dis-
tance from the radial styloid of
about 62% of the length of the radial
shaft.11 The central band functions
as an extra-articular ligament and
accounts for 71% of interosseous
membrane stiffness. It is also the
principal longitudinal stabilizer of
the radius after radial head fracture
or resection.7,12
The triangular fibrocartilage com-
plex stabilizes the radius and ulna at
the distal radioulnar joint, thus pre-
venting longitudinal displacement.3
The complex has several individual
components, of which the volar and
dorsal radioulnar ligaments are the
most important for maintaining
longitudinal stability. The dorsal
radioulnar ligament provides stabili-
ty to the distal radioulnar joint in
pronation, while the volar radioulnar
ligament does so in supination. 13
Hotchkiss et al7 demonstrated that
the triangular fibrocartilage complex
provides 8% of the forearm’s me-
chanical stiffness. Subsequent stud-
ies confirmed that the triangular
fibrocartilage complex resists proxi-
mal radial migration and participates
in load transfer.12 Moreover, Rabino-
witz et al14 suggested that clinical
migration of the radius >7 mm under
axial load implies disruption of both
the triangular fibrocartilage complex
and the interosseous ligament.
Clinical Presentation
Subtle proximal migration of the
radius usually occurs after fracture
or excision of the radial head, but it
is rarely symptomatic.5,8,9 However,
patients with greater proximal
translation may present with loss of
wrist extension and forearm rota-
tion. Positive ulnar variance from
proximal radial translation of 2 mm
increases the load maintained by the
ulna at the wrist from 20% to 40%,
potentially leading to ulnocarpal
Tamara D. Rozental, MD, et al
impaction symptoms and wrist
pain.15 Patients with proximal radial
translation >1 cm usually experience
pain and loss of motion, whereas
patients with translation <1 cm
report pain but retain motion. 16
With proximal translation of the
radius, the distal ulna loses its posi-
tion in the sigmoid notch of the
radius. The dorsal position of the
distal ulna limits supination as
the carpus abuts the ulnar head.
Loss of wrist extension occurs when
the ulnar head comes into contact
with the dorsal carpus. In addition,
proximal migration of the radius
may cause radiocapitellar abutment,
leading to elbow pain and limitation
of elbow motion.
Diagnosis
Longitudinal instability of the fore-
arm often is missed during assess-
ment at the time of injury. Although
a fracture of the radial head usually
is apparent, involvement of the in-
terosseous ligament and distal
radioulnar joint is not always appre-
ciated. A high index of suspicion
during clinical evaluation of the
wrist is essential to recognize the
injury. During the physical exami-
nation, particular attention should
be paid to whether there is tender-
ness or dorsal prominence of the
ulna at the distal radioulnar joint
and any wrist pain when gentle
rotation is applied to the forearm.
Tenderness along the forearm also
should be assessed because it may
indicate injury to the interosseous
membrane. The presence or absence
of symptoms at the forearm and
wrist should be documented clearly
in the patient’s chart.
Anteroposterior and lateral radio-
graphs of the elbow as well as pos-
teroanterior and lateral radiographs
of the wrist should be obtained
when patients present with wrist
pain or loss of motion. The optimal
view of the distal radioulnar joint is
69
Longitudinal Radioulnar Dissociation
obtained using a posteroanterior
radiograph with the shoulder at 90°
of abduction, the elbow flexed at
90°, and the forearm in neutral rota-
tion.17 However, Yeh et al18 have
shown that ulnar variance can be
assessed adequately with a routine
posteroanterior radiograph of the
wrist. Comparison radiographs of
the contralateral wrist may be useful
in select cases, and true lateral radio-
graphs may help detect dorsal sub-
luxation of the distal ulna.
In using magnetic resonance
imaging to diagnose injury to the in-
terosseous ligament, Starch and
Dabezies19 found that the ligament is
best visualized on axial T2-weighted
images. The addition of fat-suppres-
sion techniques allowed better evalu-
ation of the extent of edema in the
soft tissues. Although the authors
concluded that magnetic resonance
imaging is useful for evaluating the
interosseous ligament, clinical corre-
lations in the setting of an acute dis-
ruption have yet to be established.
Treatment
Acute Injuries
The goals of treatment of acute
injuries are restoration of load shar-
ing and prevention of proximal
migration of the radius.
Radial Head Fractures
Radial head fractures usually are
described with the Mason classifica-
tion scheme. Type I fractures are
minimally displaced and do not re-
quire surgical treatment, type II
fractures are displaced sufficiently
to require internal fixation, and type
III fractures require excision because
of excessive comminution.20
Because of its essential role in
maintaining forearm stability, the
radial head should be preserved to
prevent proximal radial migration,
especially when the secondary re-
straints to forearm stability, such as
the interosseous ligament and distal
70
radioulnar joint, have been disrupted.
Internal fixation of type II fractures
can be done with screw fixation
alone or with screws and plates when
the fracture extends to the radial
neck. Impingement at the proximal
radioulnar joint may be avoided by
placing hardware in the nonarticu-
lating safe zone of the radius. Bone
graft may be required after exten-
sive bone loss.20
In type III fractures, the radial
head cannot be repaired with inter-
nal fixation, so excision is necessary.
In patients with isolated fractures of
the radial head, excision of the frac-
tured head is a reliable form of
treatment, and excellent results are
achieved. Morrey et al9 reported an
average proximal radial migration of
1.9 mm in 13 patients and excellent
outcome in those who had radial
head excision for isolated injuries.
In patients with injury to the
interosseous ligament and distal
radioulnar joint, however, excision
of the radial head will lead to fore-
arm instability and potentially di-
sastrous consequences. Prosthetic
replacement has been advocated to
minimize the likelihood of radial
migration in such cases (Fig. 2).
Since prosthetic replacement with
ferrule caps was first described in
1941, 21 a variety of materials has
been used. Flexible Silastic radial
head prostheses implanted in the
1970s initially produced good clini-
cal results.22,23 Subsequent biome-
chanical studies, however, showed
no improvement in longitudinal
forearm stability compared with
radial head excision.7,24 In addition,
implant fracture, capitellar wear, sili-
cone synovitis, and continued radial
proximal translation were found in
long-term follow-up series.22,25-27
Metallic prostheses have become
the preferred implants. In a cadav-
eric study, Sellman et al24 noted an
increase of 145% of normal in fore-
arm stiffness after titanium radial
head replacement. Knight et al28 re-
ported good clinical success with
Journal of the American Academy of Orthopaedic Surgeons
Vitallium prostheses. Although ade-
quate elbow stability and forearm
rigidity were documented, follow-
up was short (mean, 4.5 years), and
most patients had isolated radial
head fractures without associated
ligamentous damage. A morpho-
metric study of metallic radial head
prostheses found that inadequate
sizing often leads to difficulty in fit-
ting the components,29 but recently
introduced modular implants may
eradicate this problem.
No long-term studies exist docu-
menting implant wear behavior or
clinical outcome. Additionally, there
are no published reports describing
the treatment of acute Essex-Lopresti
injuries with prosthetic radial heads.
Nonetheless, titanium and titanium
alloy implants currently are the
mainstay of treatment in prosthetic
replacement of the radial head in
cases of comminuted fractures with
associated ligamentous disruption.
Soft-Tissue Repair
Although the anatomy and func-
tional mechanics of the interosseous
ligament have been investigated
extensively, its healing potential has
not been studied. Flexor carpi radi-
alis tendon grafts have been used to
reconstruct the central band in cadav-
ers.30 On biomechanical testing, the
repair was successful in preventing
complete migration of the radius to
the capitellum but not in restoring
full longitudinal stability of the fore-
arm. Few reports of central band
repair in a clinical setting have been
published. Bone-tendon-bone graft
has been suggested, but no follow-
up data are available. Hotchkiss31
attempted one case with a palmaris
longus tendon weave, but the patient
manifested continued proximal
migration and required a salvage
procedure. Interosseous ligament
repair is not an accepted treatment
option for the management of acute
longitudinal radioulnar dissociation.
Pinning of the radius and ulna at
the distal radioulnar joint is the rec-

A B
C D
Figure 2 A 25-year-old man presented with elbow
pain and swelling after a fall from a roof. Antero-
posterior (A) and lateral (B) radiographs of the
elbow show a comminuted Mason type III fracture.
The patient was tender over the distal radioulnar
joint. C, Posteroanterior radiograph of the wrist
shows a small bone fragment (arrow) at the distal
radioulnar joint and positive ulnar variance. D,
Posteroanterior radiograph of the contralateral
wrist shows neutral ulnar variance. E, The patient
was treated with radial head excision and immedi-
ate prosthetic replacement.
E
ommended treatment for acute bilization position for dorsal ulnar
radioulnar dissociation. Patients subluxation or dislocation is in
then are immobilized in anticipation supination, maintaining the reduced
of healing of the interosseous liga- distal radioulnar joint. 32 Direct
ment and the ligaments of the distal repair of the triangular fibrocartilage
radioulnar joint. The optimal immo- and/or dorsal and volar radioulnar
Vol 11, No 1, January/February 2003
Tamara D. Rozental, MD, et al
ligaments has not been advocated
because reduction of the distal
radioulnar joint is enough to stabi-
lize the distal forearm.16
Chronic Injuries
Management is complex in
chronic cases in which longitudinal
radioulnar dissociation is diagnosed
after radial migration has occurred.
Edwards and Jupiter33 reported on
seven adults with radioulnar dislo-
cation, three of whom achieved ex-
cellent functional results when radial
length was immediately restored.
Suboptimal results were evident in
the four patients whose diagnosis
and treatment were delayed 4 to 10
weeks. Similarly, Trousdale et al34
reviewed 20 patients with radioul-
nar dissociation and found poor
clinical results in 15 patients whose
injuries were diagnosed after a mean
delay of 7 years 11 months (range, 1
month to 26 years). Treatment goals
in those cases included normaliza-
tion of the radioulnar relationship at
the distal radioulnar joint and pre-
vention of further migration of the
radius.
Restoration of the Radial Head
Szabo et al35 treated five patients
with disabling proximal migration of
the radius after radial head excision
with implantation of a frozen-allo-
graft radial head. At a mean follow-
up of 3 years (range, 1 year to 7
years), forearm rotation and wrist
motion improved and patients were
satisfied with the outcome. Al-
though these results were encourag-
ing, the number of patients and
length of follow-up were limited,
and indications for allograft radial
head replacement remain uncertain.
No published studies explore the use
of a metallic radial head prosthesis to
treat chronic radioulnar dissociation.
Length-Equalizing Procedures
Length-equalizing procedures
have been attempted in patients
with significant proximal transla-
71
Longitudinal Radioulnar Dissociation
tion. Although procedures such as
distal ulnar resection, the Sauvé-
Kapandji procedure, and segmental
shortening of the ulna reestablish
normal ulnar variance in the early
postoperative setting, they do not
restore the soft-tissue stabilizers of
the forearm, and patients experience
continued proximal radial migra-
tion.10,34,36 Ulnar shortening leads to
readjustment of the radius with con-
tinued proximal translation, pro-
ducing radiocapitellar abutment,
persistent elbow pain, and loss of
forearm rotation.
Radioulnar Arthrodesis
There are no reliable reconstruc-
tive surgical techniques to restore
forearm stability in patients with
chronic radioulnar dissociation. The
creation of a one-bone forearm, or
References
1. Curr JF, Coe WA: Dislocation of the
inferior radio-ulnar joint. Br J Surg
1946;34:74-77.
2. Essex-Lopresti P: Fractures of the
radial head with distal radio-ulnar dis-
location: Report of two cases. J Bone
Joint Surg Br 1951;33:244-247.
3. Palmer AK, Werner FW: Biomechanics
of the distal radioulnar joint. Clin
Orthop 1984;187:26-35.
4. Halls AA, Travill A: Transmission of
pressures across the elbow joint. Anat
Rec 1964;150:243-248.
5. Morrey BF, Askew L, Chao EY: Silastic
prosthetic replacement for the radial
head. J Bone Joint Surg Am 1981;63:
454-458.
6. Goldberg I, Peylan J, Yosipovitch Z:
Late results of excision of the radial
head for an isolated closed fracture.
J Bone Joint Surg Am 1986;68:675-679.
7. Hotchkiss RN, An KN, Sowa DT, Basta
S, Weiland AJ: An anatomic and
mechanical study of the interosseous
membrane of the forearm: Pathome-
chanics of proximal migration of the
radius. J Hand Surg [Am] 1989;14(2 pt
1):256-261.
8. Morrey BF, An KN, Stormont TJ: Force
transmission through the radial head.
J Bone Joint Surg Am 1988;70:250-256.
9. Morrey BF, Chao EY, Hui FC: Bio-
72
radioulnar synostosis, has been ad-
vocated as the salvage procedure
that is the most reliable solution to
this problem. A review of one-bone
forearm reconstructions done for
radioulnar instability secondary to
trauma, tumor resection, and con-
genital deformities showed good
union rates and reasonable functional
results in patients who underwent
the procedure after radial head exci-
sion.37 The optimal rotational posi-
tion of forearm synostosis is in neutral
or slight pronation,38,39 but preopera-
tive trial bracing may be useful in op-
timizing individual forearm position.
Summary
Proximal translation of the radius is
an uncommon complication after
mechanical study of the elbow follow-
ing excision of the radial head. J Bone
Joint Surg Am 1979;61:63-68.
10. Birkbeck DP, Failla JM, Hoshaw SJ,
Fyhrie DP, Schaffler M: The interos-
seous membrane affects load distribu-
tion in the forearm. J Hand Surg [Am]
1997;22:975-980.
11. McGinley JC, Kozin SH: Interosseous
membrane anatomy and functional me-
chanics. Clin Orthop 2001;383:108-122.
12. Shepard MF, Markolf KL, Dunbar AM:
Effects of radial head excision and dis-
tal radial shortening on load-sharing
in cadaver forearms. J Bone Joint Surg
Am 2001;83:92-100.
13. Adams BD, Holley KA: Strains in the
articular disk of the triangular fibrocar-
tilage complex: A biomechanical study.
J Hand Surg [Am] 1993;18:919-925.
14. Rabinowitz RS, Light TR, Havey RM, et
al: The role of the interosseous mem-
brane and triangular fibrocartilage
complex in forearm stability. J Hand
Surg [Am] 1994;19:385-393.
15. Drobner WS, Hausman MR: The distal
radioulnar joint. Hand Clin 1992;8:631-644.
16. Hotchkiss RN: Fractures of the radial
head and related instability and con-
tracture of the forearm. Instr Course
Lect 1998;47:173-177.
17. Epner RA, Bowers WH, Guilford WB:
Journal of the American Academy of Orthopaedic Surgeons
fractures of the radial head. When
recognized early, treatment involves
prevention of radial migration with
preservation of the radial head,
reduction of the distal radioulnar
joint, and, when appropriate, soft-
tissue reconstruction. When frac-
ture comminution makes primary
bony repair impossible, prosthetic
replacement of the radial head is
necessary to prevent proximal radial
migration. Although there are sev-
eral reconstructive options for treat-
ing chronic radioulnar dissociation,
such as allograft radial head replace-
ment, length equalizing, and sal-
vage procedures, no clear treatment
solutions exist. Early recognition of
longitudinal forearm instability is
critically important in the treatment
of longitudinal radioulnar dissocia-
tion.
Ulnar variance: The effect of wrist posi-
tioning and roentgen filming technique.
J Hand Surg [Am] 1982;7:298-305.
18. Yeh GL, Beredjiklian PK, Katz MA,
Steinberg DR, Bozentka DJ: Effects of
forearm rotation on the clinical evalua-
tion of ulnar variance. J Hand Surg
[Am] 2001;26:1042-1046.
19. Starch DW, Dabezies EJ: Magnetic res-
onance imaging of the interosseous
membrane of the forearm. J Bone Joint
Surg Am 2001;83:235-238.
20. Hotchkiss RN: Fractures and disloca-
tions of the elbow, in Rockwood CA Jr,
Green DP, Bucholz RW, Heckman JD
(eds): Fractures in Adults, ed 4. Phila-
delphia, PA: Lippincott-Raven, 1996, pp
929-1024.
21. Speed K: Ferrule caps for the head of
the radius. Surg Gynecol Obstet 1941;
73:845-850.
22. Carn RM, Medige J, Curtain D, Koenig
A: Silicone rubber replacement of the
severely fractured radial head. Clin
Orthop 1986;209:259-269.
23. Mackay I, Fitzgerald B, Miller JH:
Silastic replacement of the head of the
radius in trauma. J Bone Joint Surg Br
1979;61:494-497.
24. Sellman DC, Seitz WH Jr, Postak PD,
Greenwald AS: Reconstructive strate-
gies for radioulnar dissociation: A bio-

mechanical study. J Orthop Trauma
1995;9:516-522.
25. Bohl WR, Brightman E: Fracture of a
silastic radial-head prosthesis: Diagno-
sis and localization of fragments by
xerography. A case report. J Bone Joint
Surg Am 1981;63:1482-1483.
26. Mayhall WST, Tiley FT, Paluska DJ:
Fracture of a silastic radial-head pros-
thesis: Case report. J Bone Joint Surg
Am 1981;63:459-460.
27. Gordon M, Bullough PG: Synovial
and osseous inflammation in failed
silicone-rubber prostheses. J Bone Joint
Surg Am 1982;64:574-580.
28. Knight DJ, Rymaszewski LA, Amis
AA, Miller JH: Primary replacement
of the fractured radial head with a
metal prosthesis. J Bone Joint Surg Br
1993;75:572-576.
29. Beredjiklian PK, Nalbantoglu U, Potter
HG, Hotchkiss RN: Prosthetic radial
head components and proximal radial
Vol 11, No 1, January/February 2003
morphology: A mismatch. J Shoulder
Elbow Surg 1999;8:471-475.
30. Skahen JR III, Palmer AK, Werner FW,
Fortino MD: Reconstruction of the
interosseous membrane in the forearm
in cadavers. J Hand Surg [Am] 1997;22:
986-994.
31. Hotchkiss RN: Injuries to the interos-
seous ligament of the forearm. Hand
Clin 1994;10:391-398.
32. Bruckner JD, Alexander AH, Lichtman
DM: Acute dislocations of the distal
radioulnar joint. Instr Course Lect 1996;
45:27-36.
33. Edwards GS Jr, Jupiter JB: Radial
head fractures with acute distal radio-
ulnar dissociation: Essex-Lopresti
revisited. Clin Orthop 1988;234:61-69.
34. Trousdale RT, Amadio PC, Cooney
WP, Morrey BF: Radio-ulnar dissocia-
tion: A review of twenty cases. J Bone
Joint Surg Am 1992;74:1486-1497.
35. Szabo RM, Hotchkiss RN, Slater RR Jr:
Tamara D. Rozental, MD, et al
The use of frozen-allograft radial head
replacement for treatment of estab-
lished symptomatic proximal transla-
tion of the radius: Preliminary experi-
ence in five cases. J Hand Surg [Am]
1997;22:269-278.
36. Sowa DT, Hotchkiss RN, Weiland AJ:
Symptomatic proximal translation of
the radius following radial head resec-
tion. Clin Orthop 1995;317:106-113.
37. Peterson CA II, Maki S, Wood MB:
Clinical results of the one-bone fore-
arm. J Hand Surg [Am] 1995;20:609-618.
38. Wang AA, Jacobson-Petrov J, Stubin-
Amelio L, Athanasian EA: Selection of
fusion position during forearm arthrod-
esis. J Hand Surg [Am] 2000;25:842-848.
39. Chan PSH, Blazer PE, Bozentka DJ,
Gonzalez JB, Naranja RJ, Roros B:
Optimal position for the one-bone
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[Br] 1999;24:724-726.
73
 Perspectives on Modern Orthopaedics
Treatment of Chronic Discogenic Low Back Pain
With Intradiskal Electrothermal Therapy

F. Todd Wetzel, MD, and Thomas A. McNally, MD

Abstract

The treatment of chronic, nonradicular, discogenic low back pain remains con- using annular trauma in a sheep
troversial. The posterior anulus fibrosus appears to be a potential site of origin model support this theory.9 Vas-
of the pain, which is mediated by nociceptors in the inner layers of the anulus. cular ingrowth also has been ob-
Diagnosis requires a thorough history, physical examination, and imaging pro- served in peripheral tears of the
tocol; provocative diskography is key. Nonsurgical treatment options have been anulus.10 Nociceptors may accom-
limited to physical therapy and pharmacotherapy. Success rates of spinal fusion pany this vascular growth and
range from 39% to 96%. Reported therapeutic success rates of intradiskal elec- account for the presence of sensory
trothermal therapy, a possible intermediate treatment, range from 60% to 80%. nerve supply in the inner anulus.
Despite this apparent therapeutic effect, however, a more precise quantification In the normal intervertebral
of clinical benefits remains to be proved in randomized prospective trials. disk, sensory nerves do not pene-
J Am Acad Orthop Surg 2003;11:6-11 trate beyond the outer one third of
the anulus fibrosus.11-13 In degen-
erative disk disease, however, an
association has been demonstrated
Thermal energy has been shown to potential use in patients with back between ingrowth of nerves ex-
induce tissue shrinkage in cadav- pain and degenerative disk disease. pressing substance P and disk
eric1 and animal models2,3 and has To appreciate its role, it is impor- degeneration. The extent of neo-
been applied to treat peripheral tant to understand the pathophysi- neuralization has been shown to be
joint instability. Saal and Saal 4 ology and diagnosis of, and the
hypothesized that thermal energy treatment options for, degenerative
might have a role in the treatment disk disease.
Dr. Wetzel is Associate Professor of Surgery,
of so-called internal disk disrup-
Section of Orthopaedic Surgery and
tion5,6 and, thus, in chronic low back Rehabilitation Medicine and Anesthesia and
pain. This proposition led to the Pathophysiology of Disk Critical Care, University of Chicago Spine
development of a catheter to deliver Degeneration Center, Chicago, IL. Dr. McNally is Fellow in
intradiskal electrothermal therapy Spine Surgery, Section of Orthopaedic Surgery
and Rehabilitation Medicine, University of
(IDET).4 Chronic low back pain is the most
Chicago Spine Center.
Patients with chronic low back common cause of morbidity and
pain secondary to degenerative chronic pain in the United States.7
One or more of the authors or the departments
disk disease are difficult to treat Degenerative disk disease is a fre-
with which they are affiliated has received
effectively. The source or sources quent etiology of this pain;5 how- something of value from a commercial or other
of the pain may be unclear or mul- ever, the pathophysiology and party related directly or indirectly to the sub-
tiple in origin. Meticulous evalua- actual origins of the pain are in- ject of this article.
tion is key to determining optimal completely understood. One theory
therapy; however, careful evalua- hypothesizes that small, posttrau- Reprint requests: Dr. Wetzel, 4646 North
tion is complicated by the fact that matic peripheral tears of the anulus Marine Drive, 8 NW, Chicago, IL 60640.
some tests, such as diskography, fibrosus lead to an acceleration in
are controversial in relation to their the dehydration of the interverte- Copyright 2003 by the American Academy of
efficacy. IDET delivered via catheter bral disk, with resultant fraying of Orthopaedic Surgeons.
is a new technology with reported the nucleus pulposus. 8 Studies

6 Journal of the American Academy of Orthopaedic Surgeons


greatest at the painful levels. 12
Coppes et al13 noted that disk de-
generation and perhaps disk injury
are associated with centripetal
growth of nerve fibers in the disk,
which would provide a morpho-
logic basis for true discogenic pain.
The findings of these histologic
studies agree with those of clinical
studies identifying the anulus
fibrosus as a common source of the
back pain.14,15
Diagnosis and Imaging
The clinical features of internal
disk disruption, as described by
the Task Force on Taxonomy of the
International Association for the
Study of Pain, include lumbar
spinal pain, with or without re-
ferred pain, that is aggravated by
movements that stress the sympto-
matic disk. 16 The diagnosis of
internal disk disruption begins
with a thorough patient history,
physical examination, and review
of systems. Clinical characteristics
remain somewhat controversial,
but some authors have identified
extension preference (ie, patient
preference for postures that em-
phasize maintenance or exaggera-
tion of physiologic lumbar lordo-
sis) as suggestive of symptomatic
degenerative disk disease.17 Plain
radiographs, magnetic resonance
imaging (MRI), and computed
tomography (CT) are sensitive to
degenerative changes but clinically
are nonspecific. 18,19 Because it is
not possible to diagnose internal
disk disruption on clinical grounds
alone, the key to diagnosis is dis-
kography.20
While the specificity of provoca-
tive diskography remains contro-
versial,21-25 it can provide two types
of information. The morphologic
information regarding the stage of
disk degeneration is of secondary
importance because of the nonspe-
cific nature of that information in a
Vol 11, No 1, January/February 2003
F. Todd Wetzel, MD, and Thomas A. McNally, MD
clinically relevant sense. 18,19 The
more important component, precise
reproduction of the patient’s pre-
senting pain symptoms (concor-
dance), makes the test clinically use-
ful. Some studies have identified a
high level of sensitivity and speci-
ficity, whereas others have disputed
this claim.21-25 The innately subjec-
tive nature of diskography—concor-
dance pain reproduction—can never
completely be overcome. However,
with strict attention paid to tech-
nique and scrupulous insistence on
exact reproduction of the patient’s
pain, diskography may be clinically
useful. Arguably, it is the only
study whereby a painful degenerated
disk can be identified.
Treatment Options
The literature on appropriate non-
surgical treatment is confusing.
Some evidence exists supporting the
efficacy of exercise therapy,26,27 but
few definite conclusions can be
drawn. Invasive options may be
judiciously considered in patients
who remain persistently sympto-
matic. Historically, the surgical
treatment of patients with discogenic
pain without frank herniation has
been limited to lumbar arthrodesis,
but this approach lacks consensus.28
In one retrospective series of 25
patients with positive diskography
who refused surgery, 68% nonethe-
less improved. 29 The efficacy of
arthrodesis is supported by other
studies, with a rather wide range of
success rates (39% to 96%). 30-36
However, these rates are difficult to
compare directly because of differ-
ences in the criteria used to assess
success and variations in the types of
surgical procedures performed.
Even when it is relatively certain
that the pain is discogenic in origin
(ie, is not muscular or from facet
arthropathy), determining the ap-
propriate therapy is a challenge.
There is a wide gap between non-
surgical care (short periods of bed
rest for exacerbations, medications,
and physical therapy) and surgical
care (anterior, posterior, or com-
bined procedures). IDET has been
proposed as a possible treatment
between these extremes.
Intradiskal Electrothermal
Therapy
The theoretic basis for IDET is that
targeted thermal energy is designed
to shrink collagen fibrils, cauterize
granulation tissue, and coagulate
nerve tissue in the posterior anulus
fibrosus.4,37 Several studies investi-
gating the use of thermal energy
have demonstrated tissue shrinkage
in peripheral joints. Hayashi et al1
applied various temperatures to
cadaveric shoulder capsules. Above
65°C, the authors discovered shrink-
age of the specimen and, histologi-
cally, hyalinization of the collagen.1
These results were corroborated by
Obrzut et al2 in glenohumeral cap-
sular tissue from sheep. Shortening
of 14% from pretreatment resting
length was shown after thermal
lesions of 80°C; in concordance with
the results of Hayashi et al,1 tissue
shrinkage was not present at tem-
peratures below 65°C.
Further studies regarding the
mechanism and action of IDET, in-
cluding biomechanical and histo-
logic evaluation, still are required.
One recent study by Kleinstueck et
al 38 on temperature distribution
and biomechanical effects of IDET
on 13 fresh-frozen human lumbar
cadaveric specimens did not dem-
onstrate temperature production
high enough to cause nociceptive
cell death. On the surface, this
appears to discredit the theory of
deafferentation as a factor in pain
reduction. This is consistent with
the clinical finding of delayed (1 to
3 months) improvement in pain.
Kleinstueck et al38 also investi-
gated the biomechanical effects of
7
Treatment of Chronic Discogenic Low Back Pain With IDET

IDET on vertebral motion. It is

plausible that the heated catheter
denatures and shrinks the collagen
fibrils, thus stabilizing the motion
segment. In this cadaveric study,
there was an increase in motion at
the IDET-treated levels. This inves-
tigation, however, did not take into
account the effects of healing (scar-
ring) that would occur in vivo.
Healing may result in stiffening and A B
stabilization of the motion segment
over a period of time consistent Figure 1 A, Gross pathology cadaveric intervertebral disk specimen before electrothermal
with the clinical relief of pain (1 to 3 treatment. B, The same specimen after 15-minute intradiskal electrothermal treatment.
Note the shrinkage of the nuclear matrix.
months). Others 39 have noted a
similar triad of biologic repair in the
therapeutic effect (maintenance of
shrinkage, secondary scarring and many, the increased degree of nu- with biplanar fluoroscopic views
thickening, and destruction of sen- clear disorganization further serves (Fig. 2), and then thermal treatment
sory fibers). Gross pathology before to make intradiskal navigation dif- is delivered. The temperature of the
and after treatment demonstrates ficult. catheter is initially 65°C and is
shrinkage of nuclear matrix (Fig. 1). increased by 1° every 30 seconds
until the target temperature (80° to
Technique 90°) is reached and maintained for 4
Indications for IDET to 6 minutes (Fig. 3). Patients are
The procedure is done in an outpa- observed for a short period, usually
In most studies published to date, tient setting with biplanar fluo- 1 to 2 hours, then discharged.
good candidates for IDET meet the roscopy, using local anesthetic and Early clinical experience has
following criteria: low back pain of conscious intravenous sedation. shown that patients may have an
at least 3 months’ duration, with or Utilizing a standard posterolateral increase in back pain for the first
without nonradicular referred pain; Lyman Smith approach, the disk is week, then return to their baseline
failure of 3 months of nonsurgical cannulated and the thermal catheter pain level. Improvement in symp-
care; no prior surgery at the inter- positioned along the posterior anu- toms generally does not occur until 6
vertebral levels to be treated; and lus. Final catheter position is verified weeks after the procedure. During
degenerative lumbar disk disease
evident on MRI and concordant
diskography. Given the nature of
diskography and the inability to
completely eliminate all subjectivi-
ty inherent in this diagnostic proce-
dure, the importance of a meticu-
lous evaluation before intervention,
including appreciation of possible
confounding variables, cannot be
overestimated. Patients with marked
stenosis, spinal deformity (eg,
spondylolisthesis or scoliosis), or
neurologic deficit, or who are preg- A B
nant or have other confounding Figure 2 Lateral (A) and anteroposterior (B) intraoperative fluoroscopic views showing
medical conditions, are not consid- position of the catheter (arrows) during IDET procedure. This 36-year-old woman had
ered candidates. From a technical intractable lumbosacral back pain and could sit for no more than 5 minutes without severe
pain. She was unresponsive to 12 months of active physical therapy and medications.
point of view, patients with a Provocative diskography was positive at L5-S1 with negative rostral control levels.
notable loss of disk height are not Diskography revealed internal disk disruption but no full-thickness annular tearing.
appropriate candidates for IDET; in

8 Journal of the American Academy of Orthopaedic Surgeons

 F. Todd Wetzel, MD, and Thomas A. McNally, MD

100

90
T
80

Temperature (C)
70

60

50

40
C
30

20
75°C (A) 10

42°C (C) 0
60°C (B) 0 100 200 300 400 500 600 700 800 900 1,000

Time (seconds)
A B

Figure 3 Temperature distribution through the annular wall. A, Ideal position of the intradiskal electrothermal catheter (white arrow-
head) is along the posterior anulus fibrosus across the midline. The diagram indicates temperature distribution at various points (A, B, C)
in the posterior anulus at the target temperature. The temperature is 38° in the epidural space. The dark portion of the catheter represents
the heating element. B, Temperature tracing generated during lesioning. Tracing T corresponds to the temperature of the intranuclear
catheter abutting the posterior anulus. Tracing C reflects the outer annular temperature obtained by placing a sensor in the outer anulus
on the side opposite the catheter introduction.

this time, symptoms are treated with
nonsteroidal anti-inflammatory
drugs. Rehabilitation and recondi-
tioning are started after 8 to 12 weeks
to facilitate healing and maintain the
presumptive tissue shrinkage.
Activities that raise intradiskal pres-
sure, such as prolonged unsupport-
ed sitting, should be avoided.
Clinical Results
Clinical studies to date suggest a
therapeutic effect from the use of
IDET. In a series of 25 patients, Saal
and Saal4 reported reduction of two
points in the visual analog pain scale
(VAS) in 80% of patients and im-
provement in sitting tolerance and
decrease or discontinuation of pain
medication in 72%. They defined a
successful functional outcome as at
least a seven-point increase in the
Medical Outcomes Study 36-Item
Short Form (SF-36); this was
achieved in 77% of patients with sin-
gle-level disease and in 75% of
patients with two or more sympto-
matic degenerated disks. At the 2-
year follow-up of 55 patients treated
with IDET, the mean decrease in
VAS was 3.2, and the mean increase
in the SF-36 physical function sub-
scale was 20.37
In a cohort of 35 patients treated
with IDET, Karasek and Bogduk40
reported that 60% demonstrated
benefit at 1 year. They also com-
pared the outcomes of the 35
patients with those of 17 patients
who underwent a physical rehabili-
tation program. (The 17 patients
treated nonsurgically were consid-
ered candidates for IDET but had
been denied coverage by insurance
carriers.) Analysis of the two sub-
groups based on improvement in
VAS showed that 23% of the
patients in the IDET-treated group
reduced their pain level to zero at 1
year. However, because of the rela-
tively small sample size, the authors
noted that this absolute success rate
of 23% carries a 95% confidence
interval of 16%. Additionally, there
is inherent bias in the control group
because treatment was denied,
potentially imparting a negative
outcome bias to the group. At 3
months, only 1 of 17 in the control
group had improved symptomati-
cally, with no mean improvement in
VAS pain scores or increase in func-
tional activity for the group.
Thompson and Eckel41 reported
6-month follow-up data in an indus-
try-sponsored multicenter study of
170 patients. The mean decrease in
VAS was 2.6; the mean increase in
the SF-36 among six subscales was
19.1. The authors also noted increas-
es in sitting, standing, and walking
tolerance. A multicenter prospective
control cohort study of 78 patients
reported by Wetzel et al42 demon-
strated similar results. All patients
had failed nonsurgical care and had
low back pain with or without non-
radicular referred pain, one or two
levels of degenerative disease, and a
positive concordant diskography.
Of the 75% of patients who reached
the 2-year follow-up, 88% reported
they would undergo IDET again;
61% were working without restric-
tion (versus 23% before treatment).
Complications
Of all the IDET procedures done,
there has been only one reported

Vol 11, No 1, January/February 2003 9

Treatment of Chronic Discogenic Low Back Pain With IDET
case of cauda equina syndrome
caused by device malpositioning.43
This could have been avoided by
biplanar confirmation of the
catheter location before initiating
the heating cycle. Theoretic com-
plications include nerve root
injury, cerebrospinal fluid leak, and
diskitis. A 5% incidence of tran-
sient paresthesias, presumably
resulting from needle position, has
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Vol 11, No 1, January/February 2003
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Horton WC: The outcome of postero-
lateral fusion in highly selected pa-
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11
 Web and Wireless Review
Web Resources for the Electronic Medical Office
Most orthopaedic surgeons spend half their time in the
operating room, and many would prefer to spend more
there rather than devote time to office management.
Although many orthopaedic practices are well run,
there may be opportunities to improve efficiency by
using elements of the electronic office. Among medical
specialties, there has been a concerted effort to utilize
personal digital assistants (PDAs), electronic medical
records (EMRs), and computer-based management
tools. We can certainly profit from their experience.
www.aafp.org
The American Academy of Family Physicians (AAFP)
is one of the largest national medical organizations,
representing more than 93,500 members. Their web-
site (http://www.aafp.org) has a separate practice
management section with an excellent subsection on
computerization that covers PDAs, EMRs, and practice
management tools. The AAFP also offers a technology
guide produced in cooperation with Microsoft
Corporation that reviews nine software packages. All
of these have been proved to be effective in practice
and were developed and are maintained by companies
with considerable experience in practice management
software. It should come as no surprise that the last
requirement for inclusion into the survey was that the
packages use a Microsoft operating system and data-
base (Windows and SQL Server). A copy of the guide is
available for downloading at no charge at
http://www.aafp.org/PreBuilt/fpnet_techguide.pdf.
www.cpri-host.org
The Computer-Based Patient Record Institute (CPRI)
incorporated in 1992 following the recommendations of
the National Academy of Sciences, Institute of Medicine,
report Computer-Based Patient Record: An Essential
Technology for Health Care (National Academy Press,
1991, available for downloading at no charge at
http://www.nap.edu/books/0309044952/html). In
1994, CPRI, in partnership with Microelectronics and
Computer Technology Corporation (MCC), created
Healthcare Open Systems and Trials (HOST) to accelerate
the deployment of the electronic medical record. Note
that none of these entities appears to have any ties with
physician management software firms. MCC was creat-
ed in 1982 as a consortium of electronics companies,
including Hewlett-Packard, Motorola, and Texas
Instruments.
74 Journal of the American Academy of Orthopaedic Surgeons
The purpose of CPRI-HOST is to promote the uni-
versal and effective use of electronic health information
systems to improve health care delivery. One key area
on which they focus is information security, an essen-
tial element for compliance with the upcoming HIPAA
(Health Insurance Portability and Accountability Act of
1996) rules. These rules require the Department of
Health and Human Services to establish national stan-
dards for electronic health care transactions. They also
address the security and privacy of health data. The
federal government is relying on these standards to
“improve the efficiency and effectiveness of the
nation’s health care system by encouraging the wide-
spread use of electronic data interchange in health
care” (Centers for Medicare and Medicaid Services,
http://cms.hhs.gov/hipaa/). CPRI-HOST offers a
Toolkit identifying activities that health care
providers should initiate in managing information
security, including adjusting to the changing laws
and continuously updating data security policies.
The Toolkit is available for downloading at no charge
at http://www.cpri-host.org/toolkit/toc.html.
www.elmr.com
One of the most informative sites regarding EMR is
Electronic Medical Records, at http://www.elmr.com,
run in part by Kirk Voelker, MD. The site includes a
discussion forum for physicians that posts pro and con
comments from users of several software companies,
Dr. Voelker’s primer on records software, and links to
more than thirty vendor websites. One of the more use-
ful features is the EMR Worksheet, a spreadsheet-like
format with fill-in-the-blanks options for such variables
as the number of new patient charts per day, number of
chart pulls, time for filing, and savings in office space
for records. Dr. Voelker adds this comment with his
spreadsheet: “If a note takes more than 1.5 minutes
longer than usual on an EMR, you may lose money!”
Setting up an electronic medical office is a challenge
for even the best-informed individuals. Whether you
are setting up a simple electronic filing system for your
personal use, buying a physician practice management
software solution for your group, or sitting on the
EMR committee of your local hospital, these few
sources should help to make your job a little easier.
Jay D. Mabrey, MD

Orthopaedics in the
Developing World: Present
and Future Concerns
To the Editor: First I must congratu-
late the authors on a well-researched
and insightful article.1 I am a 41-
year-old African orthopaedic sur-
geon born and educated in Nigeria.
Three national orthopaedic hospitals
are dedicated to training in
orthopaedic and trauma care, and
our training has been primarily
tuned to our environment. So for
Nigeria, personnel is not a major
problem. Our problems are both
economic and political.
I presently work with the gov-
ernment of the kingdom of Lesotho
in South Africa. There are two
orthopaedic surgeons serving a
population of about 2 million peo-
ple. I work in the main hospital in
the capital. The rugged mountain
terrain, alcohol abuse (a volatile
mix), and general low socioeco-
nomic conditions lead to a high
musculoskeletal trauma rate. In
Africa generally the government
employs over 90% of medical
labour as medical care is still most-
ly seen as a social service. The
problems of African governments
impact directly on medical care.
Governments can never really pay
specialists adequately, hence the
migration of the few well-trained
personnel available. Countries
with acute shortages, like Lesotho,
have to offer “good packages” to
get personnel.
A few of the basic problems
include extremely poor record
keeping by poorly trained and
semiliterate staff (I myself have to
collect any data I want to use) as
well as very few competent assist-
Vol 11, No 1, January/February 2003
Correspondence
ing doctors. A very poor under-
standing of orthopaedic surgery by
medical administrators leads to
complaints about the cost of
implants. Another problem is
nonexistent maintenance of exist-
ing equipment. (We do have an
old C-arm. This is an absolute lux-
ury in Africa and is used sparing-
ly.) Heavy patient loads mean that
some fractures do not get fixed for
2 to 4 weeks! We lose patients to
follow-up because of distances and
poverty. Also, poor knowledge
and training of the first-contact
doctors means that a lot of fairly
simple orthopaedic cases are
already complicated by the time
they get to us. The main disasters
are with open fractures.
But having highlighted all these
problems, we do succeed reason-
ably considering the situation.
Ninety percent of my work is inter-
nal fixation of fractures. We select
patients for internal fixation care-
fully. Our fracture armamentari-
um includes the following: a mixed
range of A/O plates and screws;
Küntscher nails, which we use a lot
in imaginative ways; a few old
locking nails; tibial nails inserted
by open technique; Ender and
Rush nails, which we use some-
times with cerclage wires; and
Moore and Thompson hemiarthro-
plasties. We were able to do a few
total hip replacements a few years
ago. We also have some external
fixators.
Our infection rates are remark-
ably low. Preoperative antibiotics
continued for 48 hours, copious
irrigation of wounds, and use of
drains are, of course, standard.
What we have learned to do is to
improvise as we go along. A vital
requirement for safe improvisation
is a sound knowledge of the basic
principles. It is all pretty frustrat-
ing most of the time, but a lot of
our patients go home satisfied by
African standards! That all this can
be done in a country that is classi-
fied in the least-developed category
of the WHO classification is quite
remarkable.
Administrative ineptitude and
sheer nonchalance of the decision
makers is probably the greatest
stumbling block we face daily. The
musculoskeletal trauma load in
Africa is rising steadily, fueled by
increasing numbers of poorly
maintained cars on poorly main-
tained roads, assisted by alcohol.
All of these, combined with igno-
rance, poverty, and lack of person-
nel (internal and external brain
drain), paint a daunting picture for
the future of musculoskeletal care
in Africa.
How can the West help?
(1) By first understanding that
the greatest problems are govern-
ments. Working through them
does not work. By all means, get
permission and approval to oper-
ate, but it is better to work through
nongovernmental organisations
like the Red Cross, who already
have a local presence and know
how to get around the bottlenecks.
(2) Good basic training of doc-
tors to carry out primary proce-
dures will reduce complication
rates. Sponsoring the few local
orthopaedic surgeons and general
surgeons with an interest in
orthopaedics for training work-
shops, and then using them to run
basic practical training sessions for
the doctors at the grassroots level,
seems to me to be the most work-
75
able plan. A well-trained surgeon
will be a safe improviser when the
situation calls for it. Remember
that largely untrained doctors carry
out a lot of the surgery in the
developing world. They are usual-
ly the first contact for the patient.
(3) Adoption of the very sim-
plest techniques of fracture care
will put less strain on what is avail-
able and cut complication rates.
Any implants or equipment donat-
ed should be simple and basic. The
International Committee of the Red
Cross, for example, has very basic
and easy-to-learn protocols for frac-
ture care, to which can be added
basic internal fixation procedures
for training.
(4) Assist health ministries in
developing countries to develop
simple protocols for musculoskele-
tal trauma care, with emphasis on
simple, easily learnt and repro-
ducible methods, and to put up an
efficient referral system for more
complicated cases, with the exper-
tise and equipment for these put in
a few regional centers. Remember
that in the developing world, com-
munication systems taken for
granted in the West are luxuries.
Ambulance systems, efficient refer-
ral systems, and primary trauma
care personnel are mostly nonexis-
tent. These factors have to be taken
into consideration when designing
these protocols.
(5) Assist these health ministries
to recruit surgeons and maybe help
with remuneration of competent
African surgeons and support them
with sponsorship for practical
workshops, conferences, and sup-
ply of practical journals.
I am very interested in grass-
roots training in primary muscu-
76
loskeletal care of general care
physicians in third-world settings.
I am in the process of designing a
simple program for training our
district doctors in Lesotho in basic
fracture care. I would be interested
in hearing comments from sur-
geons who have had experience in
the area of training or who are
interested in getting into this.
D. O. Oloruntoba, MBBS, FWACS
Queen Elizabeth II Hospital
Maseru, Kingdom of Lesotho
The Author Replies: Thank you, Dr.
Oloruntoba, for your kind com-
ments on and interest in our article.1
I greatly appreciate your insight
into the current situation for
orthopaedic surgeons and patients
with musculoskeletal conditions in
both Nigeria and the kingdom of
Lesotho in South Africa. You have
provided a first-hand, succinct, and
insightful summary of the chal-
lenges and opportunities faced in
developing countries. You have
also provided sound and insightful
advice regarding how can the West
help.
While the challenges of local
infrastructure are not often easily
addressed or solved, cooperative
educational initiatives, interest, and
support are areas that organizations
such as the AAOS and Orthopaedics
Overseas (OO) are willing and in-
terested to support. The American
Academy of Orthopaedic Surgeons,
through its International Committee,
has a long history of involvement in
the developing world, primarily
through its international educational
programs. Dr. Bruce Browner
(Chairman, International Committee
Journal of the American Academy of Orthopaedic Surgeons
of the AAOS) and I recently trav-
eled to Bloemfontein, South Africa,
to represent the AAOS and OO and
meet with representatives from the
African nations at the South African
Orthopaedic Association in support
of the newly formed East Central
and South African Orthopaedic
Association (ECSAOA). The AAOS
and OO will be working with the
ECSAOA and the South African
Orthopaedic Association to orga-
nize and participate in an ortho-
paedic training course in Kampala,
Uganda, in 2004 as part of the next
ECSAOA meeting. The AAOS and
OO recognize the importance of the
formation of the first international
orthopaedic organization on the
continent of Africa and on the
importance of supporting the edu-
cational activities of the ECSAOA
and other similar groups through-
out the developing world. We
believe that through these efforts
and other grassroots training and
activities, and through the encour-
agement, enthusiasm, and commit-
ment of individuals such as you,
there is a bright future for those
with musculoskeletal conditions in
the developing world.
John P. Dormans, MD
The Children’s Hospital of
Philadelphia
University of Pennsylvania
School of Medicine
Philadelphia, Pennsylvania
Reference
1. Dormans JP, Fisher RC, Pill SG:
Orthopaedics in the developing world:
Present and future concerns. J Am
Acad Orthop Surg 2001;9:289-296.