ORIGINAL ARTICLE
Treatment of Bone Loss With the Induced Membrane
Technique: Techniques and Outcomes
Benjamin C. Taylor, MD, Jonathan Hancock, DO, Ryan Zitzke, MD, and Joaquin Castaneda, MD
Objectives: To critically review the outcomes and issues associated
with the induced membrane technique in a trauma population.
Design: Retrospective case series, Level IV therapeutic study.
Setting: Urban Level I trauma center.
Patients: Sixty-nine patients aged 18 years or older who underwent
treatment of bone loss with the induced membrane technique.
Intervention: All patients underwent open treatment of their
traumatic bone loss with a 2-stage induced membrane technique.
Main Outcome Measurement: Bony union rate, as evaluated
with radiographic and clinical signs of healing.
Results: Patients in this series averaged 4.4 surgeries, which
included initial debridement to denitive xation. The tibia was
the most common site of bone loss, encompassing 50.7% of the
series, whereas femoral bone loss was next at 24.6%. Polymethyl-
methacrylate spacers were in place for a mean of 11.2 weeks (mode
of 8 weeks) before bone grafting for an average bony defect volume
of 76.6 cm3. Union was obtained in 82.6% of patients at a mean of
26.6 weeks after grafting. Mean follow-up for these patients was
23.8 months.
Conclusions: The induced membrane technique is an effective
method to obtain bony union when used in the trauma population.
However, it is not foolproof, and attention must be paid to the
critical subtleties of the procedure. Further investigation is
needed to help determine the optimal spacer composition and
other technical aspects of the procedure such as timing of the
exchange.
Key Words: Masquelet technique, induced membrane, bone loss,
Masquelet, cement spacer
Accepted for publication March 17, 2015.
From the Department of Orthopaedic Surgery, Grant Medical Center,
Columbus, OH.
B. C. Taylor is on the speakers bureau for Depuy Synthes and AO
North America, is a consultant for Biomet, and is on the editorial
board of Orthobullets.com. The remaining authors report no conict
of interest.
Supplemental digital content is available for this article. Direct URL
citations appear in the printed text and are provided in the HTML and
PDF versions of this article on the journals Web site (www.
jorthotrauma.com).
Reprints: Benjamin C. Taylor, MD, 285 East State St, Suite 500, Columbus,
OH 43215 (e-mail: drbentaylor@gmail.com).
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Level of Evidence: Therapeutic Level IV. See Instructions for
Authors for a complete description of levels of evidence.
(J Orthop Trauma 2015;29:554557)
INTRODUCTION
Large bone defects present a complex issue for the
treating surgeon. Reported treatment options vary signicantly
and are associated with varied outcomes, prolonged healing
times, the need for multiple surgical interventions, or ampu-
tation.1 The induced membrane technique, as rst described by
Masquelet, is a relatively new approach designed to overcome
the limitations of previous limb salvage methods.24 In this
method, bone loss is treated with initial placement of a poly-
methylmethacrylate (PMMA) spacer into the defect, which
leads to a bilaminar bioactive membrane forming around the
spacer because of an inammatory response.58 The PMMA
spacer is then removed and replaced with autograft bone in
a staged fashion, where the bone graft is both protected against
resorption and incorporated by the membrane.912
Recent literature has provided evidence that the induced
membrane technique can provide excellent results with restor-
ing bone length and allowing functionality.3,4,1118 The purpose
of this study was to retrospectively investigate the outcomes of
our patients treated with this method and assess the factors
associated with success and failure of the technique. We
hypothesized that treatment of large bone defects with the
induced membrane technique would be successful in the major-
ity of cases, and that the etiology of failure for the technique
would be traced back to technical or host-related variables.
PATIENTS AND METHODS
Institutional review board approval at our institution
was obtained before initiation of the study. We initially
identied a total of 119 adult patients who had undergone the
induced membrane technique for bone loss by one of the 5
fellowship-trained orthopaedic trauma surgeons at an urban
Level I trauma facility between 2006 and 2013. Exclusion
criteria consisted of less than 12 months of postoperative
follow-up, age younger than 18 years, pregnancy at the time
of injury or follow-up, and patients who did not undergo the
second stage of the procedure.
All patients were treated with the induced membrane
technique as previously described for treatment of their
traumatic bone loss.1 This technique was used in this inves-
tigation when the amount of bone loss was signicant enough
to preclude bony union; defect sizes that successfully undergo
J Orthop Trauma  Volume 29, Number 12, December 2015
 J Orthop Trauma  Volume 29, Number 12, December 2015 Treatment of Bone Loss

this technique generally range from 2 to 20 cm. Each patient
underwent formal debridement(s) and provisional stabiliza-
tion, followed by denitive xation and PMMA spacer place-
ment when soft-tissue conditions allowed (stage 1). In all
instances, either Simplex (Stryker, Kalamazoo, MI) or Pala-
cos (Zimmer, Warsaw, IN) bone cement was used to make the
cement spacer. The PMMA spacers were impregnated with
antibiotics in 98.5% of the cases, with vancomycin being used
in all but one of those instances; addition of another heat-
stable antibiotic was performed in 29.0% of these and was
done according to surgeon preference. The PMMA spacers
were placed and shaped to match the defect in situ and allowed
to cure while in position. Retraction of the surrounding tissue
and use of sterile saline irrigation uid in the surgical eld were
used to minimize risks of thermal injury. The spacer was then
exchanged for autogenous bone graft as a second stage. The
second stage of the procedure was generally scheduled at 8
weeks after spacer placement to allow for membrane maturation
(Fig. 1 and see Figures, Supplemental Digital Content 14,
http://links.lww.com/BOT/A375, http://links.lww.com/BOT/A376,
http://links.lww.com/BOT/A377, http://links.lww.com/BOT/A378).
General demographic data for the study population
were collected from hospital and clinic charts, and the results
are shown in Supplemental Digital Content 5 (see Table,
http://links.lww.com/BOT/A371). All radiographs, including
from the time of injury, after initial/repeat debridement and
stabilization, after nal xation and spacer placement, after
spacer removal and bone grafting, and at each follow-up
appointment, were reviewed by a senior orthopaedic resident
and fellowship-trained orthopaedic traumatologist. Follow-up
data and radiographs were also collected, reviewed, and pre-
sented in the tables and the results section to follow.
After data collection, stats were analyzed with mean
values, ranges, and condence intervals (CIs) calculated for
continuous variables and compared using Student t tests. Fre-
quencies were calculated for continuous variables and com-
pared using Fisher exact test for increased accuracy in small
proportion analysis. A signicance level of P . 0.05 was set as
signicant, with a trend being dened as a P value between
0.05 and 0.10.
RESULTS
A total of 69 patients met inclusion criteria and were
included in this study (see Table 1, Supplemental Digital
Content 5, http://links.lww.com/BOT/A371). There were 35
tibias, 16 femurs, 6 radii, 6 humeri, 2 calcanei, two rst
metatarsals, one fth metacarpal, and 1 ulna treated with
the induced membrane technique. The patient population
was predominantly male (73.9%), with the mean age being
42.3 6 16.9 years. Relatively few comorbidities were discov-
ered, although the rate of tobacco use was fairly high (43.5%).
Injury characteristics are shown in Supplemental Dig-
ital Content 6 (see Table, http://links.lww.com/BOT/A372).
The majority of the open injuries were classied as a Gustilo
Anderson Type III (69.6%), indicating a high level of energy

FIGURE 1. A, The view shows the injury radiograph of a grade 3B open distal tibia fracture. B, The view shows the anteroposterior
radiograph of the injury after PMMA placement. The image (C) shows the thick membrane that formed at 8 weeks after PMMA
insertion, whereas images (D, E) show the injured limb 2 years after PMMA removal and autologous bone graft placement.
Editors note: A color image accompanies the online version of this article.

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 Taylor et al
imparted to the affected area. Compartment syndrome was
diagnosed in 7.2% of the series, and 46.4% had other ortho-
paedic injuries requiring surgical intervention.
Patients underwent a mean of 1.6 6 1.4 debridements
before nal cement spacer placement (see Table 3, Supple-
mental Digital Content 7, http://links.lww.com/BOT/A373).
Mean bone loss after debridement was 5.0 6 2.9 cm, with the
maximum length of bone loss being 14 cm in this series (see
Tables, Supplemental Digital Content 7 and 8, http://links.
lww.com/BOT/A373, http://links.lww.com/BOT/A374). Crit-
ical review of the radiographs found that 84.1% of the
PMMA spacers were overlapping the ends of the intact bone,
with the remainder truly overlapping only 1 end of the intact
bone at the end of the gap. The spacer was maintained in
position for the rst stage of the procedure for a mean of
11.2 6 13.0 weeks, with the mode being 8 weeks after inser-
tion. At the second stage of the procedure, autologous bone
graft was obtained from the femur using the reamerirrigator
aspirator system (Synthes, West Chester, PA) in 66.7% of
cases, with iliac crest bone graft harvest making up the
remainder of the cases. Adjunct allograft was used in
43.5% of the cases as a bone graft expander, with osteoin-
ductive agents (rhBMP-2 or OP-1) used in 23.2% of cases.
Use of the osteoinductive agents was done solely at the begin-
ning of the data collection period in an off-label effort by
several of the surgeons to maximize bony healing potential.
An average of 0.86 mL of cancellous allograft was used per
milliliter of cancellous autograft in this cohort.
Follow-up length for this series was 23.8 6 14.2 months
(range 1264 months), and successful union was obtained in
82.6% of patients at a mean of 26.6 6 29.3 weeks after graft
insertion. Infection was a risk inherent to these injury patterns,
and this series was no different. We found 7 patients with deep
infection requiring operative debridement after PMMA spacer
placement (13.0%). Interestingly, despite repeat operative
debridement and a benign appearing surgical eld at the time
of bone graft placement, only 1 patient had negative intraoper-
ative deep cultures during this second stage. The 6 patients
who had positive intraoperative deep cultures were treated with
6 weeks of intravenous antibiotics and maintenance of the im-
plants and bone graft; 4 of these patients went on to successful
union, whereas the other 2 went on to amputation. Four pa-
tients (5.8%) developed a deep infection after bone grafting
who previously did not have an infection, and all went on to
clinical and radiographic union after debridement, intravenous
antibiotics, and maintenance of the graft and implant(s).
Nonunions of one or both ends of the bone gap were
found in 12 patients (17.4%), but the only signicant risk
factors for nonunion were as follows: postgrafting infection
(relative risk = 11.8, 95% CI: 4.431.9), postoperative wound
dehiscence (relative risk = 9.7, 95% CI: 4.322.1), and infec-
tion before grafting (relative risk = 2.9, 95% CI: 1.17.9). We
were unable to discover any differences in union for several
pertinent variables, including patient age, tobacco use, diabetes,
head injury, type of open injury, number of debridements,
length or volume of bone loss, type of cement or antibiotic
used, timing of spacer removal and grafting, type or amount
of graft used, type of xation used, or need for soft-tissue
coverage. Of the 12 nonunions, 5 of these patients underwent
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J Orthop Trauma  Volume 29, Number 12, December 2015
revision xation and additional bone grafting, and all of these
went on to successful radiographic and clinical union. Two of
the patients with nonunions were asymptomatic and refused
surgery, 2 were lost to follow-up, 2 underwent delayed ampu-
tation, and 1 patient died 3 years later due to an unrelated cause.
DISCUSSION
Union rates for the induced membrane technique have
been reported as high as 100%, and the union rate for our
series was 82.6%.2 The only signicant risk factors discov-
ered for nonunion in our series were related to bone infection
and wound complications; no differences in outcomes with
infected patients were seen with development of infection at
any particular stage. Addition of bone morphogenic proteins
to the nal bone graft was performed in 16 cases early in the
study collection period, but this did not show any signicant
change in union or complication rates despite the increased
cost of using such materials. In addition, we were unable to
nd any difference in union rate with use of allograft; simi-
larly, we did not nd any differences in the union or compli-
cation rate according to the proportion of allograft and
autograft bone. Outcomes did not differ regarding location
of bony decit, which segment of bone was involved (diaph-
ysis or metaphysis), or type of implant chosen (external
xation, intramedullary nails, or plate and screw constructs).
We were unable to determine an optimal range for
timing of PMMA spacer removal and grafting from our series.
Current recommendations for spacer exchange range from 4 to
8 weeks, but these suggestions are largely based on anecdotal
or limited evidence.2,3,8 We did notice an improvement in qual-
ity of the membrane spacer as the spacer was left in situ for at
least 6 weeks; the membrane seemed to reach peak thickness
and subjective quality as reported by the operating surgeons at
this time point. We did notice a relative decrease in the thick-
ness and subjective quality of the patients who had the second
stage of the procedure delayed by more than 20 weeks; the 5
patients who underwent grafting at this time point or later were
for delayed soft-tissue healing (2), patient incarceration (2), or
patient social reasons (1). Although some evidence already
exists, further translational research in this area would help
greatly in determining the optimal timing for spacer
exchange.5,6,8 Similarly, little to no evidence exists on the opti-
mal composition of the spacer; the optimal type of cement, use
of noncement alternatives, and utilization of antibiotics all
remain under question at this point in time.
We did hypothesize that lack of overlap of the PMMA
spacer over the ends of the intact bone surrounding the gap
would lead to an increased rate of nonunion, but we were
unable to support this hypothesis. Intraoperatively, these
cases did have membranes that did not overlap the ends of
the bone, but this aspect of the membrane was removed by the
surgeon to reopen the medullary canals of the adjacent bone
end to improve vascularity. However, to minimize this issue,
we still recommend overlap of the cement spacer over the
ends of the bone, because this allows the maximum amount of
the membrane to be maintained in position, which should
allow the bone graft to be placed around the end of the bone
and to be protected by the bioactive membrane.
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 J Orthop Trauma  Volume 29, Number 12, December 2015
As with any retrospective analysis, we do note several
inherent weaknesses of this analysis. We were only able to
include a total of 58% of the patients treated with this
technique because of the inclusion and exclusion criteria, with
the majority of the exclusions being due to inadequate follow-
up. An improved follow-up rate would potentially allow
discovery of other important ndings, and the increased
power from a larger series would also allow improved data
analysis. We also note a wide variety of anatomic regions and
xation constructs in this series, although we were unable to
determine any statistically signicant ndings between any of
these variables. We do not have any patient-reported scoring
systems in this investigation, but with the heterogenous
collection of patients, injuries, and treatment methods, we
did not believe that this was warranted.
Large segmental defects in bone with a trauma patient
continue to present signicant challenge to treating surgeons.
We believe that the induced membrane technique provides
another treatment method to provide bone stability to patients
with this type of injury. This study provides additional
supporting data validating its usefulness and is the second
largest collection of patients with this technique in the literature
at this juncture.4 Further investigation into this technique will
continue to provide additional data on the subtleties of the pro-
cedure, which should optimize healing and clinical outcomes.
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