Induced membrane technique for the treatment of chronic hematogenous tibia osteomyelitis

Abstract

Background
Chronic hematogenous osteomyelitis often results from the improper treatment of acute hematogenous osteomyelitis. At present, there is lack of uniform standards for the treatment, and the clinical features of the disease are unclear. The purpose of this study was to explore the clinical efficacy and complications of chronic hematogenous tibia osteomyelitis treated with the induced membrane technique. MethodsA retrospective analysis of the chronic hematogenous tibia osteomyelitis patients in our department admitted from January 2013 to February 2014 and treated with the induced membrane two-stage surgical technique was performed. The defects were filled with antibiotic-loaded polymethyl methacrylate (PMMA) cement after radical debridement, and bone grafts were implanted to repair the defects after 6 to 8 weeks. ResultsA total of 15 cases were admitted in this study, including 13 men and 2 women with a mean age of 34 years (6 to 51). The mean duration of bone infection was 142 months (3 to 361). All patients were cured with an average follow-up of 25 months (24 to 28). Radiographic bone union occurred in 5.3 months (3 to 8), and full weight bearing occurred in 6.7 months (4 to 10). No recurrence of infection was noted at the last follow-up. Two cases required repeated debridement before grafting due to recurrent infection. One patient had a small bone diameter due to insufficient grafting, and one patient had limitation of knee activity. Conclusions
The induced membrane technique for the treatment of chronic hematogenous tibia osteomyelitis is an effective and reliable method. Thorough debridement and wound closure at the first stage is essential for infection control as well as sufficient grafting at the second stage to ensure bone union.

Full text

R E S E A R C H A R T I C L E Open Access
Induced membrane technique for the
treatment of chronic hematogenous tibia
osteomyelitis
Xiaohua Wang
†
, Zhen Wang
†
, Jingshu Fu, Ke Huang and Zhao Xie
*
Abstract
Background: Chronic hematogenous osteomyelitis often results from the improper treatment of acute hematogenous
osteomyelitis. At present, there is lack of uniform standards for the treatment, and the clinical features of the disease are
unclear. The purpose of this study was to explore the clinical efficacy and complications of chronic hematogenous tibia
osteomyelitis treated with the induced membrane technique.
Methods: A retrospective analysis of the chronic hematogenous tibia osteomyelitis patients in our department
admitted from January 2013 to February 2014 and treated with the induced membrane two-stage surgical
technique was performed. The defects were filled with antibiotic-loaded polymethyl methacrylate (PMMA)
cement after radical debridement, and bone grafts were implanted to repair the defects after 6 to 8 weeks.
Results: A total of 15 cases were admitted in this study, including 13 men and 2 women with a mean age of
34 years (6 to 51). The mean duration of bone infection was 142 months (3 to 361). All patients were cured with
an average follow-up of 25 months (24 to 28). Radiographic bone union occurred in 5.3 months (3 to 8), and full
weight bearing occurred in 6.7 months (4 to 10). No recurrence of infection was noted at the last follow-up. Two
cases required repeated debridement before grafting due to recurrent infection. One patient had a small bone
diameter due to insufficient grafting, and one patient had limitation of knee activity.
Conclusions: The induced membrane technique for the treatment of chronic hematogenous tibia osteomyelitis
is an effective and reliable method. Thorough debridement and wound closure at the first stage is essential for
infection control as well as sufficient grafting at the second stage to ensure bone union.
Keywords: Induced membrane, Two-stage surgery, Hematogenous osteomyelitis
Background
Any form of inflammation involving bone tissue or mar-
row caused by a pathogenic organism is called osteomye-
litis [1]. The condition mostly occurs at the metaphyseal
of immunocompetent patients [2]. Hematogenous
osteomyelitis is rare in developed countries but remains
a serious problem in less developed regions. Chronic
hematogenous osteomyelitis mainly occurs in long
bones. In a rural African setting, tibia osteomyelitis was
noted in 21.6% of these patients [3]. Adult hematogenous
osteomyelitis was mostly persistent from childhood [4].
Blood flow is slower at the growth bone site, so the bac-
teria deposited cause acute osteomyelitis [5]. If not treated
in time or with improper treatment, the condition will
persist and become chronic osteomyelitis. Although great
progress has made in the treatment of osteomyelitis, there
is no standard for clinicians to use. According to our
knowledge, few reports on the treatment of chronic
hematogenous tibia osteomyelitis are available, and the
characteristics of the disease are unclear. In recent years,
Masquelet reported [6] a two-stage surgical method for
the treatment bone defects, which is called induced
membrane technique, and acquired great success. This
technique is recognized and used in the treatment of
* Correspondence: xiezhao54981@163.com
†
Equal contributors
National & Regional United Engineering Laboratory of Tissue Engineering,
Department of Orthopaedics, Southwest Hospital, Third Military Medical
University, Chongqing 400038, People’s Republic of China
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33
DOI 10.1186/s12891-017-1395-6
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

osteomyelitis [7]. We reported the use of the induced
membrane technique for the treatment of 32 cases
post-traumatic osteomyelitis and obtained good clinical
efficacy [8]. Here, we performed a retrospective analysis
of 15 patients with chronic hematogenous tibia osteo-
myelitis treated with the induced membrane two-stage
surgical technique to assess the clinical outcome and
provide a reference for this disease.
Methods
After approval by the Ethics Committee, we retrospect-
ively analyzed chronic hematogenous tibia osteomyelitis
patients in our department from January 2013 to February
2014. The inclusion criteria were (1) historical evidence of
radiological and clinical bone infection at the tibia; (2) no
historical evidence of open fracture or fracture internal
fixation at the involved site; (3) local bone pain and swell-
ing on examination, imaging procedures, microbiology
and histopathology, and laboratory studies [8]. The gold
standard for diagnosis of osteomyelitis is biopsy or culture
from deep tissue [9] frozen sections confirmed to have
more than five neutrophils per high-power field. Those
with insufficient information or with Cierny-Mader C
stage, which is inoperable, were excluded. We collected
the patient's age, sex, Cierny-Mader host stages, duration
of bone infection, culture, fixation and grafting type by pa-
tient record systems.
Seventeen cases were treated with this technique, and
two were excluded due to incomplete information. Thus,
a total of 15 patients were reviewed (Table 1), including
13 men and 2 women with a mean age of 34 years (6 to
51). The mean duration of bone infection was
142 months (3 to 361). Six (40%) cases had a history of
collision, and 11 (73.3%) patients were younger than
20 years old at their initial onset. There were 6 cases in
the proximal tibia, 7 cases in the middle tibia, and 2 in
the distal tibia. No patient had diabetes, immune defi-
ciency diseases or peripheral vascular diseases. Two
cases were classified as Cierny-Mader type II, 8 cases as
type III and 5 cases as type IV. Eleven cases had draining
sinus tracts or local redness and swelling, and the
remaining 4 cases had a history of osteomyelitis. The
main clinical manifestations were long-term pain at the
involved site, and radiological examination revealed bone
destruction. Nine patients had bacterial cultures contain-
ing 11 strains, including 4 strains of Staphylococcus aur-
eus,2Proteus,1Enterobacter cloacae,1Micrococcus
luteus, 1 hemolytic Staphylococcus, 1 fecal Enterococcus
1Klebsiella oxytoca.
All patients were treated with the induced membrane
technique. The defects were filled with antibiotic-
loaded PMMA cement after radical debridement at the
first stage. Then, bone graft was implanted to rebuild
bonedefectsatthesecondstage.Therangeofdebride-
ment was determined with preoperative X-ray, CT,
MRI and bone scintigraphy examinations [10, 11]. The
sinus was removed, and the sequestrum was cleaned.
Surrounding necrosis tissue and scar tissue should be
Table 1 Patient demographics
Patient
number/sex
Location Cierny-Mader
types
Skin
ulcer
Duration
of infection
Bacterium Bone
defect (cm3)
Fixation Time to
WB/S2
(Months)
Istage IIstage
1/M Proximal III YES 30Y Enterobacter cloacae 75 external
fixation
external
fixation
6
2/M Middle IV YES 16Y Staphylococcus aureus 30 EP EP 7
3/M Middle III NO 7Y Micrococcus luteus 45 external
fixation
external
fixation
7
4/M Proximal IV NO 10Y Not found 60 EP EP 9
5/F Middle III NO 7 M Not found 25 EP EP 4
6/M Middle III NO 2Y Not found 35 IP IP 7
7/M Proximal III NO 9 M Not found 42 IP IP 6
8/M Distal III YES 3 M Staphylococcus aureus 20 IP IP 4
9/M Proximal II NO 30Y Staphylococcus hominis,
Efaecium
84 None None 7
10/M Proximal IV YES 31Y Proteus mirabilis 75 EP Nail 10
11/M Distal II YES 13 M Staphylococcus aureus 42 None None 6
12/F Middle III NO 6 M Not found 30 EP Nail 6
13/M Middle IV YES 28Y Staphylococcus aureus 60 EP Nail 9
14/M Middle IV YES 2Y Proteus mirabilis, Klebsiella 80 IP Nail 8
15/M Proximal III NO 18Y Not found 40 IP IP 5
WB/S2: No pain full-weight bearing after the second stage; EP and IP: External and internal fixation with plate and screws
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 2 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

removed because it causes tension, decreases the rate
of wound healing, and acts as foci for infection [12].
The sequestrum and surrounding tissues are used for
culture and pathological examination. The bone ends
are subject to grinding until signs of bleeding, and the
medullary cavity is reamed. The wound is washed with
hydrogen peroxide, dilute povidone-iodine and saline
repeatedly. After effective fixation, the defects are filled
with 40 g PMMA cement (Heraeus, Germany) mixed
with 5 ~ 10 g vancomycin (Eli Lilly, Japan). The cement
should be packed in the bone ends and not be smaller
than the diameter of the tibia. If internal fixation is
used, the cement should wrap the bone. Then, suction
drainage tubes are inserted, and the wound is closed. A
local or distant flap will be useful for high skin tension.
If infection recurs, repeated debridement was per-
formed until the infection was controlled. Intravenous
injections of sensitive antibiotics are administered for
two weeks postoperatively based on the drug sensitivity
tests. If the culture is negative, a third generation ceph-
alosporin (Ceftazidime, Hailin, China) is administered
at a dose of 2 g per 12 h. Suction drainage is performed
for 10 ~ 12 d. Weight-bearing should not be performed
between the first and second stages.
Grafting was performed 6 to 8 weeks later, with a
mean interval time of 50 days (44 to 105). The situation
of infection control should be assessed before grafting,
including the presentation of signs, such as redness,
sinus and pus, or abnormal laboratory tests, such as
erythrocyte sedimentation rate, CRP and white blood
cell count. These indicators could reveal recurrent infec-
tion, which requires debridement until the infection is
under control. The amount of the graft is estimated
based on CT measurement before surgery [13]. The ce-
ment is removed, and the canals are reamed. The wound
is washed. The graft is cut to 0.5 cm × 0.5 cm × 0.5 cm
in size. The induced membrane is grafted and sutured.
Prophylactic antibiotics are administered for 24 h, and
suction drainage is applied for 10 ~ 12 days.
Patients underwent follow-up at 1, 2, 3, 6, 9, 12, 18,
and 24 months. We assessed the time to bone healing,
infection control, local pain, range of knee movement,
lower limb edema, ability to walk and other complica-
tions. Gradual ambulation until callus was observed.
Our clinical endpoints were 24 months after the second
stage until infection control and the X-ray scan revealed
bone union. CT scans were performed when X-ray did
not clearly indicate bone union. We defined radiographic
healing as bridging callus on three of four cortices and
clinical healing as pain-free full weight bearing [13].
Results
The average volume of bone defects was 51.3 cm
3
(20 to
84 cm
3
) after debridement. Three patients were implanted
with autografts, 6 with autograft plus variable proportion
of allograft and 5 with allograft for more than 25% of the
total volume. Five children and one adult were implanted
with allograft only. At the first stage, external fixations
were used in 8 cases, 5 cases with internal fixation, five
cases were replaced with nail at the second stage, and 2
cases with no fixation.
All the patients achieved bone union within the mean
follow-up of 25 months (24 to 28), and no infection re-
currence was noted. The mean radiographic bone union
occurred in 5.3 months (3 to 8), and painless weight
bearing was noted at 6.7 months (4 to 10). A compari-
son of the bone union time of three groups (allograft,
allograft + autograft and autograft) did not reveal statisti-
cally significant differences (Table 2). Two patients
required repeated debridement before grafting due to re-
current infection. Two cases with pin tract infection
were noted when external fixation was used. Infection
was controlled after the removal of the screw and topical
sterilization. Four cases had dull pain or edema of the
leg after activity. We recommended the use of symptom-
atic treatment and elastic stockings to reduce edema.
Four cases had donor site pain and discomfort. One case
had a small tibia diameter at the defect site (Fig. 1). One
case had limitation of knee limb activity (0–85°). After
an average of 25 months of follow-up, we observed no
infection recurrence, and no lasting damage to bone was
noted in all patients. Typical cases are presented in
Fig. 2.
Discussion
Chronic osteomyelitis is a serious problem for orthope-
dists given the lack of a generally accepted method for
treatment. Classic techniques include Ilizarov technique,
one stage bone grafting and vascularized fibula graft.
These techniques are often associated with high compli-
cations or long-term recurrence rates [14–16]. Some re-
ports have described the use of the induced membrane
Table 2 Patients with different grafting
Graft type Cases Average age Average bone defect (cm3) Time to BU/S2 (Months) Time to WB/S2 (Months)
Autograft 3 46.7Y 38.3 5.0 6.4
Autograft + Allograft 6 42.2Y 67.3 6.3 7.8
Allograft 6 19Y 37.3 4.5 5.8
BU and WB/S2:Radiographic bone union and no pain full-weight bearing after the second stage
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 3 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Fig. 1 Case 10, 50 Y, repeated swelling and skin ulcer of the right proximal tibia for more than 30 years. Proteus mirabilis was identified. aand b:
Sinuses were observed, and X-ray revealed bone destruction; c: Complete resection of the lesions and implantation with PMMA cement after the
second stage; d: Grafting (autograft 60 ml +allograft 15 ml) eight weeks later; e: X-ray revealed bone union at 6 months; f: 20 months after the
second stage, bone union with a small diameter was noted
Fig. 2 Case 8, 6 Y, Redness and painful left tibia for 3 M. The patient had a history of a fall 2 weeks before the illness; however, fracture and skin
breakdown were not noted. Bone reconstruction was performed with an allograft. a: X-ray revealed bone destruction of the distal tibia;
b: Implanted with PMMA cement and fixed with plate after debridement; c: X-ray revealed bone union 3 months after grafting; d:The
bone defects were completely healed, and fixation was removed after 18 months
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 4 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

technique in the reconstruction of long bone defects,
but this technique has not been specifically studied in
the treatment of osteomyelitis [4]. We applied the in-
duced membrane technique for the treatment of chronic
hematogenous tibia osteomyelitis. The process involves a
series of measures, including radical debridement re-
moval of necrotic tissue, elimination of dead space,
drainage, skin covering and stable fixation for infection
control. Then, a membrane is formed by implantation of
a PMMA cement, and grafting the induced membrane
approximately 8 weeks later. The membrane rapidly pro-
motes bone defect repair [8].
Hematogenous osteomyelitis mostly occurs at the
metaphyseal of children and less frequently in immuno-
competent adults [2]. Local injury is an important factor
for hematogenous osteomyelitis [17, 18]. Our results re-
vealed that 6 (40%) patients had a history of collision at
the involved site. Eleven (73.3%) patients were younger
than 20 years old at their first outbreak, and these re-
sults were similar to a previous study. However, four im-
munocompetent adults with an initial outbreak were
included. Clinical symptoms of chronic osteomyelitis in-
clude blurry vision, dull pain, chills and fever [10].
Staphylococcus aureus is the most common pathogen
for bone and joint hematogenous osteomyelitis [19, 20],
Staphylococcus aureus,Streptococcus and anaerobic bac-
teria accounted for 80% of all pathogens [21]. However,
the proportion of bacteria may be altered with the
course of the migration and surgical procedures. Our re-
sults showed that 9 patients were positive for 11 strains
of bacteria. Staphylococcus aureus accounted for 26.7%
(4 strains) of bacteria strains. Bacteria obtained from
sinus secretions may not be reliable because the patho-
gens are often inconsistent with the deep tissue [10, 22].
Our positive bacterial rate was only 60% (9/15) for 5-day
cultures. Sheehy SH et al. [23] reported a 64% positive
rate with a 7-day culture, so they suggested prolonging
the incubation time to 14 days.
Antibiotic therapy alone can acquire good clinical effi-
cacy for acute hematogenous osteomyelitis, but chronic
osteomyelitis often requires surgery due to the presence
of a sequestrum [24]. Systemic antibiotics for osteomye-
litis are generally administered for 4 to 6 weeks [25, 26].
However, this value is only based on empirical data. No
study has demonstrated that 4 to 6 weeks of antibiotics
can be more effective [10, 27]. Salgado reported the use
of muscle versus non-muscle flaps for the treatment of
chronic tibia osteomyelitis in animals, antibiotics for
5 days postoperatively, and no recurrence of infection
within 1-year follow-up [28]. Knopp [29] reported 47
cases of chronic osteomyelitis, and intravenous antibi-
otics were administered for 3 to 5 days with an infection
control rate of 85%. We used intravenous antibiotic ther-
apy for approximately 2 weeks after the operation. No
oral antibiotics were used given that radical debridement
can disrupt bacterial biofilm formation, reduce bacterial
load, improve the local blood supply, and enhance the
efficiency of antibiotics. All of these measures prevent
the further formation of bacterial biofilm and reduce the
incidence of systemic adverse reactions [30]. If the sur-
geon is confident of thorough debridement, a shorter
antibiotic time can be selected. If the skin and soft tissue
conditions permit, we can also choose internal fixation,
such as open fracture (contaminated wound), but the
surface of the plate should be wrapped with bone ce-
ment. Bhaskar Borgohain [31] reported on an 8-year-old
child. In this case, sequestrum disappeared with intra-
venous antibiotics and supportive treatment for 8 months
without surgical intervention, but the shorter follow-up
may exclude long-term infection recurrence.
The classic technique for the treatment of chronic
osteomyelitis is often accompanied by complications.
Muscle flap to fill the cavity is often applied, but it may
affect the aesthetic and limit the function of donor site
[28, 32]. Complications for treating hematogenous
osteomyelitis include myositis, soft tissue abscess, fasci-
itis or blood borne complications, such as DVT [20].
Our results indicated that the complications mainly in-
cluded leg edema, donor site pain and pin-track infec-
tion when external fixation was applied. Knee flexion is
a limitation for proximal tibia osteomyelitis. One patient
exhibited a small diameter of the tibia because the graft-
ing affected wound closure. We reduced the volume of
graft, so we recommend using a larger amount of ce-
ment compared with the corresponding diameter of the
tibia at the first stage. Tibia osteomyelitis is often associ-
ated with skin defects. If large skin tension is noted after
suturing, adjacent flap or skin graft can be necessary.
Autograft is still the main source of the bone for this
technique. Numerous studies indicated that greater than
25% bone substitute should not be added [33, 34].
Eleven (5 Autograft + Allograft and 6 Allograft) cases in
our study were implanted with greater than 25% of the
total volume of the allograft given that the PMMA ce-
ment induced the formation of a membrane, which is
conducive to rapid healing of bone defects. We used a
stem cell enrichment device to mix the autologous bone
marrow with the allograft. Most patients had a partial
bone defect with an increased repair ability. Children
may be able to generate a periosteal membrane faster
than adults [7], but their bone healing time was not sig-
nificantly reduced in this study. This result could pos-
sibly be attributed to the fact that a greater proportion
of the allograft was used for our skeletally immature pa-
tients. Formerly, we reported the induced membrane for
the treatment of posttraumatic osteomyelitis [8]. When
comparing the current results with our previous study
on the application of the induced membrane technique
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 5 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

of post-traumatic osteomyelitis, we found similar clinical
efficacy and complications.
Conclusions
The induced membrane two-stage surgical strategy for
the treatment of chronic hematogenous tibia osteomye-
litis is a clinically stable and reliable method. Thorough
debridement and wound closure at the first stage, ad-
equate grafting at the second stage and early functional
exercises are necessary to achieve good clinical efficacy.
Abbreviations
CRP: C-reactive protein; CT: Computed tomography; DVT: Deep vein
thrombosis; MRI: Magnetic resonance imaging; PMMA: Polymethyl
methacrylate.
Acknowledgements
Not applicable.
Funding
The Funding of State Key Laboratory of trauma, Burns and Combined
Injury(SKLKF201313), and the key project of Logistics Research Plan of
PLA(BWS13C014) supported the design, data collection and manuscript writing
of this study. There was no funding of this study by any commercial sources.
Availability of data and materials
We are unable to share the raw data because ethical approval was not
obtained for data sharing. In addition, all data are presented in the tables.
Authors’contributions
XW contributed to data collection, paper writing, data analysis, and
performed surgeries. ZW contributed to data collection, data analysis,
performed surgeries, and paper writing. JF contributed to data collection.
KH contributed to data collection. ZX contributed to overall planning, data
analysis, and performed surgeries. All authors have read and approved the
final version of this manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Ethics approval was obtained from the Southwest Hospital, Third Military
Medical University Ethics Committee. All the participants had written
informed consent.
Received: 13 July 2016 Accepted: 12 January 2017
References
1. Agarwal A, Aggarwal AN. Bone and Joint Infections in Children: Acute
Hematogenous Osteomyelitis. Indian J Pediatr. 2016;83(8):817–24.
2. Thein R, Tenenbaum S, Chechick O, et al. Delay in diagnosis of femoral
hematogenous osteomyelitis in adults: an elusive disease with poor
outcome. Isr Med Assoc J. 2013;15(2):85–8.
3. Ibingira CB. Chronic osteomyelitis in a Ugandan rural setting. East Afr Med J.
2003;80(5):242–6.
4. Sanders J, Mauffrey C. Long bone osteomyelitis in adults: fundamental
concepts and current techniques. Orthopedics. 2013;36(5):368–75.
5. Shiels SM, Bedigrew KM, Wenke JC. Development of a hematogenous implant-
related infection in a rat model. BMC Musculoskelet Disord. 2015;16:255.
6. Masquelet AC, Fitoussi F, Begue T, et al. Reconstruction of the long bones
by the induced membrane and spongy autograft. Annales de chirurgie
plastique et esthetique. 2000;45(3):346–53.
7. Canavese F, Corradin M, Khan A, et al. Successful treatment of chronic
osteomyelitis in children with debridement, antibiotic-laden cement spacer
and bone graft substitute. Eur J Orthop Surg Traumatol. 2016:1-8.
8. Wang X, Luo F, Huang K, et al. Induced membrane technique for the
treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint
Res. 2016;5(3):101–5.
9. Mouzopoulos G, Kanakaris NK, Kontakis G, et al. Management of bone
infections in adults: the surgeon's and microbiologist's perspectives. Injury.
2011;42 Suppl 5:S18–23.
10. Haidar R, Der Boghossian A, Atiyeh B. Duration of post-surgical antibiotics in
chronic osteomyelitis: empiric or evidence-based? Int J Infect Dis. 2010;14(9):
e752–758.
11. Tetsworth K, Cierny G, 3rd. Osteomyelitis debridement techniques. Clin
Orthop Relat Res. 1999;360(360):87–96.
12. Parsons B, Strauss E. Surgical management of chronic osteomyelitis. Am J
Surg. 2004;188(1):57–66.
13. Stafford PR, Norris BL. Reamer-irrigator-aspirator bone graft and bi
Masquelet technique for segmental bone defect nonunions: a review of 25
cases. Injury. 2010;41 Suppl 2:S72–77.
14. Dendrinos GK, Kontos S, Lyritsis E. Use of the Ilizarov technique for
treatment of non-union of the tibia associated with infection. J Bone Joint
Surg Am. 1995;77(6):835–46.
15. Gao YS, Ai ZS, Yu XW, et al. Free vascularised fibular grafting combined with
a locking plate for massive bone defects in the lower limbs: a retrospective
analysis of fibular hypertrophy in 18 cases. Injury. 2012;43(7):1090–5.
16. Giannoudis PV, Faour O, Goff T, et al. Masquelet technique for the
treatment of bone defects: tips-tricks and future directions. Injury. 2011;
42(6):591–8.
17. Hwang HJ, Jeong WK, Lee DH, et al. Acute Primary Hematogenous
Osteomyelitis in the Epiphysis of the Distal Tibia: A Case Report With
Review of the Literature. J Foot Ankle Surg. 2016;55(3):600-604.
18. Manche E, Rombouts-Godin V, Rombouts JJ. Acute hematogenous
osteomyelitis due to ordinary germs in children with closed injuries. Study
of a series of 44 cases. Acta Orthop Belg. 1991;57(2):91–6.
19. Agrawal R, Sharma D, Dhiman P, et al. Clinical and haematological
predictors of acute hematogenous Methicillin Resistant Staphylococcus
aureus (MRSA) osteomyelitis & septic arthritis. J Orthop. 2015;12(3):137–41.
20. Ratnayake K, Davis AJ, Brown L. Pediatric acute osteomyelitis in the
postvaccine, methicillin-resistant Staphylococcus aureus era. Am J Emerg
Med. 2015;33(10):1420–4.
21. Osman AE, Mubasher M, ElSheikh NE, et al. Investigation of polymorphisms
in anti-inflammatory cytokine genes in hematogenous osteomyelitis. Genet
Mol Res. 2015;14(4):16981–6.
22. Perry CR, Pearson RL, Miller GA. Accuracy of cultures of material from swabbing
of the superficial aspect of the wound and needle biopsy in the preoperative
assessment of osteomyelitis. J Bone Joint Surg Am. 1991;73(5):745–9.
23. Sheehy SH, Atkins BA, Bejon P, et al. The microbiology of chronic
osteomyelitis: prevalence of resistance to common empirical anti-microbial
regimens. J Infect. 2010;60(5):338–43.
24. Rao N, Ziran BH, Lipsky BA. Treating osteomyelitis: antibiotics and surgery.
Plast Reconstr Surg. 2011;127 Suppl 1:177S–87S.
25. Lazzarini L, Mader JT, Calhoun JH. Osteomyelitis in long bones. J Bone Joint
Surg Am. 2004;86-A(10):2305–18.
26. Mader JT, Shirtliff ME, Bergquist SC. Antimicrobial treatment of chronic
osteomyelitis. Clin Orthop Relat Res. 1999;360:47–65.
27. Shuford JA, Steckelberg JM. Role of oral antimicrobial therapy in the
management of osteomyelitis. Curr Opin Infect Dis. 2003;16(6):515–9.
28. Salgado CJ, Mardini S, Jamali AA, et al. Muscle versus nonmuscle flaps in the
reconstruction of chronic osteomyelitis defects. Plast Reconstr Surg. 2006;
118(6):1401–11.
29. Knopp W, Kiztan T, Muhr G. Soft tissue covers in chronic osteitis. Handchir
Mikrochir Plast Chir. 1987;19(2):98–103.
30. Henry SL, Seligson D, Mangino P. Antibiotic-impregnated beads. Part I: Bead
implantation versus systemic therapy. Orthop Rev. 1991;20(3):242–7.
31. Bhaskar Borgohain NB, Tashi Khonglah. Complete incorporation of long
diaphyseal sequestrum without surgical intervention in chronic
hematogenous osteomyelitis of tibia in an immunocompetent child. Adv
Biomed Res. 2014; 3(1):95.
32. Rubino C, Figus A, Mazzocchi M, et al. The propeller flap for chronic
osteomyelitis of the lower extremities: a case report. Journal of plastic,
reconstructive & aesthetic surgery. JPRAS. 2009;62(10):e401–404.
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 6 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

33. Masquelet AC. Muscle reconstruction in reconstructive surgery: soft tissue
repair and long bone reconstruction. Langenbeck's archives of surgery /
Deutsche Gesellschaft fur Chirurgie. 2003;388(5):344–6.
34. Masquelet AC, Begue T. The concept of induced membrane for
reconstruction of long bone defects. Orthop Clin North Am. 2010;41(1):
27–37. table of contents.
• We accept pre-submission inquiries
• Our selector tool helps you to find the most relevant journal
• We provide round the clock customer support
• Convenient online submission
• Thorough peer review
• Inclusion in PubMed and all major indexing services
• Maximum visibility for your research
Submit your manuscript at
www.biomedcentral.com/submit
Submit your next manuscript to BioMed Central
and we will help you at every step:
Wang et al. BMC Musculoskeletal Disorders (2017) 18:33 Page 7 of 7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com