Injury, Int. J.
Care Injured 47 (2016) 2051–2052
Contents lists available at ScienceDirect
Injury
journal homepage: www.elsevier.com/locate/injury
Editorial
Masquelet technique for the treatment of segmental bone loss have we
made any progress?
Managing post-traumatic or post infectious segmental bone
defect poses numerous challenges to the orthopaedic trauma
surgeon. The aim of the treatment is to obtain an outcome as close
as possible to patients’ expectations. This is arduous and requires
thorough communication with the patients and their families to
understand their desires. Options such as amputation, shortening or
segmental defect reconstruction are available and well described.
When a decision has been made to proceed with segmental bone
loss reconstruction, the induced membrane technique is a good
surgical strategy with fairly predictable outcomes. The popularity of
this method of treatment has increased in recent years thanks to its
reproducibility, the fact that it remains the technique that least
depends on patients compliance (when compared to bone
transport) and that it is in ‘theory’ length independent. The use
of RIA to harvest autologous bone graft for the second stage has
made large segmental defects easier to ‘‘fill’’.
In 2016, Fischer et al. [1] published an excellent basic science
paper comparing serum levels of TGF-b1, PDGF-AB and IGF-1 for a
period of 6 months in three groups of patients. Group 1 included
patients with a successful Masquelet technique, group 2 patients with
a failed Masquelet and group 3 patients with a healed long bone
fracture. The study revealed that successful bone reconstruction using
the induced membrane technique was only partially comparable to
physiologic bone healing in terms of cytokine expression with high
levels of IGF1 corresponding to a successful Masquelet while a minor
role seemed to be played by TGF b1. This may set the ground for
clinical predictability studies of outcome to inform on future success
or failure of treatment using the induced membrane technique.
The ideal antibiotic, its dosing and the type of cement to use for
the first stage remains unanswered. The effect of different
antibiotics and cements on the membrane itself was recently
studied in an animal model [2], revealing that both the thickness
and the proportion of elastic fibers varied significantly according to
the antibiotic and cement used. Unfortunately, the authors did not
look specifically into how those differences in the membrane
structure affected bone healing.
Innovative strategies have been described using antibiotic
carbon fiber interlocked nails for the second stage of the Masquelet
technique. Our group from Denver Health has published data on
the benefits including MR compatibility to monitor the response to
treatment [3]. A detailed and innovative way to fabricate antibiotic
nails using chest tubing [4] with the addition of sterile mineral oil
within the plastic tubing system combined with a bath of cold
sterile saline during the hardening phase of the cement prevents
adhesion of the plastic to the cement and greatly facilitates
removal of the plastic around the antibiotic nail when used to
stabilize a segmental bone defect.
http://dx.doi.org/10.1016/j.injury.2016.09.018
0020–1383/ß 2016 Published by Elsevier Ltd.
Little is known about the ideal fixation means for both the first
stage and second stage. The original technique describes the use of
external fixation, however concerns for external fixator placement
for a period of 6 weeks or more remains. Proponents of IM nails
argue that the implant occupies the medullary cavity allowing for
angiogenesis and less quantity of autologous bone graft.
In a recently published case series [5] of 8 cases of segmental
bone loss reconstruction using the Masquelet technique, there was
a trend to earlier weight bearing, better mechanical alignment and
lower volume of graft needed when patients were fixed with an IM
nail versus plate fixation.
Probably one of the largest clinical series to date was reported by
Azi et al. [6] with 34 critical segmental bone defects (mean size of
6.7 cm) of the femur and tibia (70% infection), treated with the
induced membrane technique. The authors achieved bone union in
90% of cases at an average time of 8.5 months. One third of infectious
cases recurred revealing the difficulty in treating chronic osteomye-
litis and the importance of risk stratification and shared decision
making for patients with bone loss as a result of an infectious process.
Despite such advances, a number of important questions
remain unanswered leaving orthopaedic trauma and reconstruc-
tive surgeons with minimal guidance on certain key aspects of the
treatment modality.
Anatomical location of the segmental defect: Indeed, while the
Cierny and Mader classification scheme may be useful, it does not
take into account of the anatomical location of the segmental
defect/infection focus, which has drastic implications on the
treatment algorithm and strategy. While it is challenging to tackle
a diaphyseal segmental defect using the induced membrane
technique, metaphyseal segmental defects must be stabilized
using either a plate (which in the setting of an infection may be
counter productive) or a fine wire ring fixator due to the small
amount of metaphyseal bone available for fixation.
The importance of risk stratification: We are familiar with the
importance of the host on the outcome of the technique.
Unfortunately the majority of patients that present with a diagnosis
of post traumatic diffuse osteomyelitis are poor hosts. It is therefore
critical to work on risk stratification schemes at the time of the initial
traumatic injury where a window of opportunity can be utilized to
adapt the treatment and be more aggressive. The CDC’s National
Healthcare Safety Network’s (NHSN) current risk adjustment model
for surgical site infections (SSI) following open reduction internal
fixation (ORIF) of long bone fractures may not be the most accurate
predictor of risk, taking into account criteria such as the size of the
hospital rather then the fact that a fracture was open to calculate
relative risk of surgical site infection. Of the 39 different SSI risk
predictor models, 23 (59%) have a c-score of <0.70, questioning the
2052 Editorial / Injury, Int. J. Care Injured 47 (2016) 2051–2052
predictability of risk [7]. Some of our unpublished data have shown
that age (odds ratio: 1.0, p-value: 0.10, 95% confidence interval: 1.0–
1.1), ASA grade (2.9, 0.01, 1.2–6.6) and history of MRSA (7.2, <0.01,
1.8–28.9) as being important independent predictors of SSI in
Orthopaedic trauma following fixation of fractures. A c index of 0.75
(NHSN model has a C index of 0.65), indicated that our model was
superior in estimating infection risk. When our new stratification
model was used to predict the number of expected infections on a
novel dataset from 2014 to 2015, 26.7 SSI were expected compared to
8.5 calculated by the NHSN model. Such scientific strategies may
allow surgeons to anticipate an infection based on specific injury/
patient criteria and treat them prophylactically accordingly.
Intraoperative assessment of what to debride: At least in the setting
of osteomyelitis, a key ingredient if not the most important one is
the quality of the debridement. Currently, this critical intraoperative
decision process relies upon surgeons’ experience and gut feeling
using modalities such as the bleeding (or lack of) from the diseased
bone when drilling a hole (Paprika sign). This test must be done
without tourniquet and there is in our view a large intra and inter
observer variability to it. The appearance of the surrounding tissue
and consistency of the bone can also guide the debridement.
Which cement and what antibiotics at what dosage?: As
demonstrated by Nau et al. [2], the characteristics of the
membrane can be very different based on the type of antibiotic
and cement utilized. Our current experience is to use normal
viscosity Palacos cement 1 or 2 bags based on the size of the defect.
We mix 3.6 grams of tobramycin and 3 g of Vancomycin per bag of
cement and add an extra monomer (liquid). If this extra monomer
is not added the sandy cement is not moldable. It is important to
note that Alain Masquelet (ACM) does not use antibiotics in his
cement spacer and encourages this practice to avoid masking a sub
acute infection and rather focuses on the quality and extent of bony
debridement to clean and bleeding margins.
What is the ideal implant to stabilize a diaphyseal defect?: The
question of which implants to use for the first and second stages of the
Masquelet technique remains unanswered. A large variability in
practices exists based on preferences and location of the defect
making any meta-analysis or consensus difficult. Antibiotic nails are
interesting because they have in theory less affinity to biofilm, are
load-sharing devices and occupy the medullary cavity reducing the
quantity of bone graft required at the second stage. They are in theory
more patient friendly then external fixation devices. Plates are load-
bearing devices that may attract bacteria and biofilm formation. The
number of screws and their location in relation to the defect will affect
the micro motion at the defect and therefore the speed of union. The
use of external fixators as originally described is ideal in the setting of
infection especially during the first stage of the technique. One of the
concerns with this strategy is the use of external fixation for a
prolonged period of time and converted to a plate or a nail for the
second stage. This puts the patient at an increased risk of infection and
we recommend the use of hydroxy-apatite coated pins.
Negative margins before second stage: When treating osteomye-
litis, control of the infection prior to the second stage is essential.
However very few recommendations exist on how this should be
achieved. We recommend interruption of oral/parenteral antibio-
tics for one week prior to open biopsy at both ends of the segmental
defect. Samples should be sent for both microbiology and pathology
to confirm eradication/control of the infection. A week later, if those
specimens are clear, the second stage can be initiated.
What is the best bone graft and what is its ideal density?: An
increasing body of literature suggests that the use of Reamer Irrigator
Aspirator (RIA) to harvest autologous bone graft is at least equivalent
or superior to iliac crest bone graft. A recent paper from Nodzo et al.
[8] confirmed a higher non-union rate in the ICBG group compared to
patients undergoing ankle arthrodesis using RIA. In the setting of
segmental defect reconstruction, it is important to understand the
fine balance (difficult to quantify) between the quantity of autologous
bone graft harvested using RIA (to obtain osteoinduction and osteo-
genicity) and the importance of having ‘‘loose graft’’ rather then a
tight cylinder. One must resist this latter tendency to allow for
angiogenesis to occur. The idea of combining RIA autograft to
cancellous bone chips may reduce the graft density and favor angio-
genesis. It is important to close the membrane if possible to prevent
the mixture of allo/autograft from migrating away from the site.
The induced membrane technique remains an art where
surgeons’ experience, personal preference and ‘‘gut feeling’’ are
heavily relied upon more so than well powered prospective work
and evidenced based recommendations. The issue here remains
the large variability of presentations of patients, their pathology,
comorbidities and associated injuries in addition to the lack of FDA
approval of certain components of the treatment such as antibiotic
loaded cement spacers, antibiotic nails, antibiotic beads prevent-
ing IRB approval of prospective work. The solution is to create a
task force of a dozen of experts, to come up with solutions to those
highlighted problems and reach a consensus using the Delphi
method to standardize practices and inform practices.
References
[1] Fischer C, Doll J, Tanner M, Bruckner T, Zimmermann G, Helbig L, et al. Quantifi-
cation of TGF-b1, PDGF and IGF-1 cytokine expression after fracture treatment
vs. non-union therapy via masquelet. Injury 2016;47(February (2)):342–9.
[2] Nau C, Seebach C, Trumm A, Schaible A, Kontradowitz K, Meier S, et al. Alter-
ation of Masquelet’s induced membrane characteristics by different kinds of
antibiotic enriched bone cement in a critical size defect model in the rat’s femur.
Injury 2016;47(February (2)):325–34.
[3] Mauffrey C, Hake ME, Chadayammuri V, Masquelet AC. Reconstruction of long
bone infections using the induced membrane technique: tips and tricks. J
Orthop Trauma 2016;30(June (6)):e188–93.
[4] Kim JW, Cuellar DO, Hao J, Seligson D, Mauffrey C. Custom-made antibiotic
cement nails: a comparative study of different fabrication techniques. Injury
2014;45(August (8)):1179–84.
[5] Olesen UK, Eckardt H, Bosemark P, Paulsen AW, Dahl B, Hede A. The Masquelet
technique of induced membrane for healing of bone defects. A review of 8 cases.
Injury 2015;46(December (Suppl. 8)):S44–7.
[6] Azi ML, Teixeira A, Cotias RB, Joeris A, Kfuri M. Membrane induced osteogenesis
in the management of post-traumatic bone defects. J Orthop Trauma
2016;(April) [Epub ahead of print].
[7] Mu Y, Edwards JR, Horan TC, Berrios-Torres SI, Fridkin SK. Improving risk-
adjusted measures of surgical site infection for the national healthcare safety
network. Infect Control Hosp Epidemiol 2011;32:970–86.
[8] Nodzo SR, Kaplan NB, Hohman DW, Ritter CA. A radiographic and clinical
comparison of reamer-irrigator-aspirator versus iliac crest bone graft in ankle
arthrodesis. Int Orthop 2014;38(June (6)):1199–203.
Cyril Mauffrey MD, FACS, FRCS*
Department of Orthopaedics, Denver Health Medical Center,
University of Colorado, School of Medicine, 777 Bannock Street,
Denver, CO 80204, United States
Peter V. Giannoudis MB, BSc, MD, FACS, FRCS(Eng)a,b
a
Professor, Academic Department of Trauma & Orthopaedics, School of
Medicine, University of Leeds, Leeds, UK
b
NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, LS7
4SA, West Yorkshire, Leeds, UK
Janet D. Conway MD
Department of Orthopedics, Rubin institute for advanced orthopedics,
Baltimore, USA
Joe R. Hsu MD
Department of Orthopedics, Carolinas Healthcare system, Charlotte, USA
Alain-Charles Masquelet MD
Department of Orthopaedics, Hôpital Saint-Antoine, Paris, France
*Corresponding author
E-mail address: cyril.mauffrey@dhha.org (C. Mauffrey).