M u s c u l o s k e l e t a l I m a g i n g • C l i n i c a l Pe r s p e c t i ve
Porrino et al.
Femoral Fractures and Bisphosphonate Therapy
Musculoskeletal Imaging
Clinical Perspective
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Diagnosis of Proximal Femoral
Insufficiency Fractures in Patients
Receiving Bisphosphonate Therapy
Jack A. Porrino, Jr.1 OBJECTIVE. The purpose of this article is to describe the imaging features of proximal
Chad A. Kohl femoral insufficiency fractures in patients on long-term bisphosphonate therapy.
Mihra Taljanovic CONCLUSION. The imaging findings of bisphosphonate-related femoral insufficiency
Lee F. Rogers fractures, which include a typical proximal diaphyseal location and transverse liner radiolu-
cency through localized thickening of the lateral cortex, allow a specific diagnosis.
Porrino JA Jr, Kohl CA, Taljanovic M, Rogers LF
I
nsufficiency fractures occur in
abnormal bone—that is, bone com-
monly affected by generalized
osteoporosis—as a result of nor-
mal activity such as walking. There are several
reports identifying a strong relationship be-
tween prolonged receipt of bisphosphonate
therapy and insufficiency fractures of the prox-
imal femur among postmenopausal women
[1–8]. To date, to our knowledge, there is only
one report in the radiologic literature describ-
ing these fractures [2].
The proximal femur is routinely exposed to
high-energy maximal-bending movements [2,
8]. Fractures within this region require high
energy if the bone mineralization is normal.
Insufficiency fractures in the osteoporotic
population in this region are said to be rare
[2, 7, 9]. Fractures, or fracturelike conditions,
within this area in the absence of high-ener-
gy trauma can occur in other clinical settings
but are either related to unusual causes, such
as pyknodysostosis or fluoride therapy, or pro-
Keywords: bisphosphonate, femur, fracture, insuffi- vide differentiating radiographic and clinical
ciency, subtrochanteric clues [7, 10–15]. Therefore, when a proximal
femoral diaphyseal fracture is identified in the
DOI:10.2214/AJR.09.3383
appropriate demographic after low-energy
Received July 29, 2009; accepted after revision trauma, one should consider the possibility of
October 15, 2009. long-term bisphosphonate therapy as the un-
1
derlying cause.
All authors: Department of Radiology, University of
Arizona, 1501 N Campbell Ave., Tucson, AZ 85724.
Although the exact mechanism for bisphos­
Address correspondence to phonate-related insufficiency fracture of the
L. F. Rogers (lfrogers@comcast.net). proximal femur is not yet entirely understood,
a relationship is evident [4, 5, 9]. It seems a par-
AJR 2010; 194:1061–1064 adox that a fracture would be associated with
0361–803X/10/1944–1061
bisphosphonate therapy because bisphospho-
nates are prescribed for generalized osteopo-
© American Roentgen Ray Society rosis to increase bone mineral density and de-
AJR:194, April 2010 1061
crease the chance of fracture. Bisphosphonates
function by inhibiting bone resorption by sup-
pressing osteoclasts through apoptosis [7, 8].
Although this action results in increased bone
mineral density, suppressed bone turnover pre-
vents remodeling and healing of cracks that
occur in bone as a result of normal activity, of-
ten referred to as microdamage [6–8].
The characteristic clinical and imaging
findings of bisphosphonate-related proximal
femoral insufficiency fracture are described
in detail, with comparison made to other
causes of proximal femoral shaft fractures in
the setting of a low-energy inciting event.
Materials and Methods
Ethical approval was obtained by the Univer-
sity of Arizona’s institutional review board be-
fore commencement of the study. From January
through October 2009, we searched for cases of
transverse fractures involving the proximal femur
in postmenopausal women with the previously
reported characteristic radiographic appearance
suggestive of insufficiency injury related to long-
term bisphosphonate therapy.
When an insufficient-appearing proximal fe-
mur fracture was identified, the images were inde-
pendently reviewed by three radiologists, and
characteristics were classified. Specifically, the lo-
cation of the fracture with respect to the femoral
shaft, the presence of localized lateral cortical
thickening, and the appearance of the fracture
lucency (transverse, oblique, or comminuted) were
documented. Medical records were retrospectively
reviewed to determine patient demographics, history
of oral bisphosphonate therapy, most recent docu-
mented bone mineral density, when available, and
presentation of injury.
 Porrino et al.

Results
Medical records confirmed prolonged (> 3
years) oral bisphosphonate use of various
agents in four patients with findings sugges-
tive of insufficiency fracture related to long-
term bisphosphonate therapy. The four post-
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alendronate for at least 3 years before injury.
In addition, patients 1 and 3 switched to iban-
dronate sodium and risedronate, respectively,
before fracture. Each patient was receiving an
oral bisphosphonate at the time of fracture. The
most recent lumbar spine bone mineral den-
mented bone mineral density score in their
current medical record.
All four patients reported a low-energy in-
citing event as the cause for presentation. For
several months, patient 1 had reported thigh
pain that was misdiagnosed as being statin

menopausal women ranged in age from 57 sity T score for patient 1, acquired over 1 year related. Upon stepping off a scale at her cli-
to 77 years at the time of injury, with a mean before fracture, was −2. Patients 2, 3, and 4 nician’s office, she heard a “pop” followed by
age of 66.5 years. All four patients had taken were treated for osteoporosis without a docu- weakness and eventually fell to the ground.

A B C

Fig. 1—Beak appearance of bisphosphonate-related

proximal femoral shaft fracture in precomplete
fracture stage.
a, Femoral shaft fracture (arrow) in patient 1, a
77-year-old woman, is shown.
B, Enlargement of boxed area in A is shown.
C, Femoral shaft fracture (arrow) in patient 2, a
66-year-old woman, is shown.
D, Enlargement of boxed area in C is shown.
E, Contralateral femur of patient 2 shows thickening
of lateral cortex without linear fracture lucency.
D E

1062 AJR:194, April 2010

 Femoral Fractures and Bisphosphonate Therapy
Patient 2 stated that she suffered from non-
remitting left thigh pain that was worst dur-
ing ambulation for 1 month before presenta-
tion to the emergency department. Patient 3
tripped over a small step while exiting her
home and heard a “crack” with the next step.
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No prior thigh or groin pain was document-
ed in records. Before the injury, patient 4
reported suffering from pain in the lateral
aspect of her hip and groin, which was mis-
diagnosed as sciatica. She tripped at an un-
specified event, falling from ground level,
and felt severe pain in her leg.
Patient 1 presented 5 days before complete
fracture with complaints of hip pain. The an-
teroposterior radiograph of the affected hip
acquired on initial presentation included the
proximal femoral shaft; however, the insuffi-
ciency fracture was overlooked. Characteristic
features were seen in retrospect on complete
fracture. In addition, patient 1 incurred a sim-
ilar fracture in the contralateral femur 1 year
before her current injury. Patient 2 presented
to the emergency department in the precom-
plete fracture stage, before displacement, with
less-pronounced findings evident in the con-
tralateral femur. Patients 3 and 4 presented
Fig. 2—Bisphosphonate-related proximal femur
fracture before open reduction and internal fixation
in patient 3, a 66-year-old woman. Lateral cortex of
fracture is sharp and perpendicular to long axis of
cortex. There is flare or beak of compact periosteal
callus at outer margin of lateral cortex of both
proximal and distal fragments at fracture line.
AJR:194, April 2010 1063
with a completely displaced transverse frac-
ture of the proximal femoral diaphysis.
In the precomplete fracture stage of the
disease, we found the radiographic findings
to be subtle and easy to overlook. The insuf-
ficiency fracture lies within the lateral cortex
of the proximal femur. It presents as a trans-
verse fracture line through a localized area
of thickening involving the lateral aspect of
the cortex [1, 6–8]. The appearance of the
fracture mimics that of a “tibial striation,”
or stress fracture, seen in the anterior cortex
of the tibia. Such cortical thickening along
the lateral, or tension, side of the femur is ap-
parent before eventual complete fracture, as
seen in patients 1 and 2 (Fig. 1).
The underlying nature of the fracture was
also evident on radiographs of the complete
fracture of the femur before and after open
reduction and internal fixation (Figs. 2 and
3). These fractures are treated with a tro-
chanteric-entry nail, either one or two proxi-
mal lag screws, and distal interlocking screw
fixation. The reduction is usually complete,
and the apposition is often immediate. This,
in effect, restores the appearance of the in-
sufficiency fracture in the lateral cortex.
A B
Fig. 3—Postreduction radiographs in patient 4, a 57-year-old woman, also show underlying nature of fracture.
A, Smooth, transverse nature of original fracture of lateral cortex and beaked margins (arrow) can be seen.
B, Enlargement of boxed area in A is shown.
Discussion
Most patients with bisphosphonate-relat-
ed proximal femoral insufficiency fractures
have noted nonspecific prodromal pain in
the affected thigh or groin, which has often
been misconstrued or misdiagnosed as be-
ing due to degenerative disease of the low-
er lumbar spine and sacroiliac joints [7, 8].
Many patients present with a complete and
significantly displaced fracture of the proxi-
mal femoral shaft as a result.
The imaging characteristics of bisphospho-
nate-related insufficiency fractures that we
describe are, in our experience, unique and
easily recognized by a trained observer. Sim-
ilar insufficiency fractures among patients
not receiving bisphosphonates are extreme-
ly rare. Schilcher and Aspenberg [9] report a
study of 91,956 women older than 55 years of
whom 3,087 (3.4%) were receiving continu-
ous treatment with bisphosphonate drugs. The
overall incidence of insufficiency fractures of
the femoral shaft in patients receiving con-
tinuous bisphosphonates was 1 per 1,000 an-
nually (95% CI, 0.3–2), compared with 0.02
per 1,000 (95% CI, 0.004–0.1) for untreated
women. Schilcher and Aspenberg calculat-

ed the relative risk and found a 46 times in-
creased risk of insufficiency fractures for pa-
tients taking bisphosphonates. Thus, when a
fracture of the femoral shaft is identified in an
older patient with the characteristic imaging
features we have described, it is highly likely
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that the patient has been receiving long-term
bisphosphonate therapy [9].
Fractures, or fracturelike conditions, with-
in the proximal femoral diaphysis seen in the
setting of low-energy trauma do occur in other
clinical situations. These include stress fractures
(fractures involving normal bone subject to a re-
petitive stress), pseudofractures of osteomalacia,
and pathologic fractures [10]. However, the clin-
ical presentation and imaging features of these
entities provide differentiating clues.
Stress fractures occur in young military re-
cruits and athletes and involve the medial cortex
when in the proximal femur [10–15]. This area of
the proximal femur is susceptible to stress frac-
ture because of the origin of the vastus medialis
and insertion of the adductor brevis [11]. Con-
versely, insufficiency fractures occur in the elder-
ly and involve the lateral cortex. Radiographs of
stress fractures, when positive, typically show
foci of periosteal reaction with an obliquely ori-
ented linear lucency within the medial cortex [10,
11, 13]. Alternatively, insufficiency fractures typi-
cally present as focal cortical thickening with a
transverse lucency within the lateral cortex. Many
insufficiency fractures present with completely
displaced fractures of the femoral shaft, whereas
such complete fractures in femoral stress fracture
are uncommon [15].
Pseudofractures, or Looser zones, also
show a transverse lucency through the cor-
tex of the femur, but again involve the me-
dial cortex and are often multiple and with-
out significant associated cortical thickening
[16, 17]. These findings are considered char-
acteristic of primary osteomalacia [10].
Pathologic fractures of the proximal femoral
diaphysis are nearly always transverse and typ-
ically are due to metastatic disease, Paget dis-
ease, or fractures through preexisting Looser
zones. When they are caused by metastatic
disease, these fractures show poorly defined
lucent margins, an aggressive bone marrow
1064 AJR:194, April 2010
Porrino et al.
pattern of destruction, and endosteal scalloping
[10, 17]. Fractures related to Paget disease show
one or more fracture lucencies projecting
through the cortex along the convex margin of
the femur; however, concomitant deformity of
the femoral shaft is also present [10].
Although our patients did not undergo
MRI or nuclear medicine imaging, a case re-
port by Bush and Chew [2] describes these
findings. The technetium-99m–labeled meth-
ylene diphosphonate bone scan appearance
is that of a focus of increased uptake within
the lateral cortex of the affected proximal fe-
mur. MRI of the pelvis revealed a thickened
lateral cortex with a focus of abnormally
high signal. The contralateral femur showed
similar findings [2].
Prior data suggest that a significant percent-
age of patients with evidence of cortical stress
in this region or insufficiency fracture have
similar findings in the contralateral femur,
such as that seen in patient 2 (Fig. 1E). Involve-
ment of the contralateral femur varies in the lit-
erature, ranging from 20% to 64% [3, 6–8]. It
is advisable to image the contralateral femur if
characteristic findings are apparent [3, 5–8].
When the radiologist encounters fractures
involving the proximal femur in the setting of
a low-energy inciting event, demographic and
historical information should be sought. This
information, in conjunction with the radiolog-
ic findings, can lead to a correct diagnosis. A
transverse fracture of the proximal femur with
associated localized thickening of the lateral
cortex in a postmenopausal woman receiving
long-term bisphosphonate therapy should be
considered diagnostic for a bisphosphonate-
related insufficiency fracture.
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