Osteomyelitis is a challenge for orthopedic surgeons. Bone provides a unique harbor for microorganisms that produce biofilms, allowing them to attach resiliently to biologic and implanted surfaces while remaining insusceptible to host defenses. Acute and chronic phases of osteomyelitis are differentiated by both pathophysiology and treatment algorithms. Hippocrates first described the disease, recommending splinting and clean dressings for open fractures and highlighting the risk of bone infection.1 Ambroise Paré, a French surgeon, described his own open tibia fracture that developed an infection, and attributed this to retained humor.2 Warfare in the 20th century spurred advances in plastic and orthopedic surgery and, along with the introduction of penicillin in the 1940s, pointed the treatment of osteomyelitis in the direction that has taken today.3
Unfortunately, the management of osteomyelitis has been given too little attention to date, and quality clinical trials to support treatment practice are scarce. The variability in practice and lack of standardization highlights the latter statement. A treatment algorithm that is based on a classification scheme with a poor interobserver variability can contribute to this difficulty. Furthermore, few centers treat a high volume of patients that would be sufficient to develop evidence-based algorithms. Finally, surgical methods aimed at local excision of the lesion are bound to failure; the infected tissue within bone has the potential to spread, and wide excision with clear margins is the most valid treatment philosophy. In this article, the fundamental concepts behind the disease process are reviewed and the current techniques for the management of osteomyelitis are discussed. An algorithm for treatment based on these concepts and techniques is presented and illustrated using clinical examples.
Although many breakthroughs have been made in the field of infectious disease over the past decades, osteomyelitis remains a difficult problem for the orthopedic community, particularly in busy trauma centers that care for open and complex fractures. Infection rates in open long bone fractures range from 4% to 64%.4 A recent study showed that even in patients receiving state-of-the-art orthopedic and plastic surgical care, 23% of patients developed infections after an average of 3 procedures per limb.5 Chronic infections are both expensive and challenging to treat and cure rates are still not optimal. Ideally, treatment methods should offer complete resolution of infection and optimized function and mobility of the affected extremity. Currently, despite advances in both surgical and chemical treatment, recurrence rates following bony infection are between 20% and 30%.6
Several classification systems have been devised for osteomyelitis, but the Cierny-Mader system remains the most clinically relevant. This system stratifies hosts into 3 categories (A–C) based on physiologic comorbidities and designates 4 anatomic stages of infection (1–4), which are combined to produce 12 classifications.7 This system assists in clinical decision making for the extent of surgical debridement, as well as antibiotic therapy.
Host factors are important in determining treatment algorithms. According to the Cierny-Mader system, a type A host is a healthy patient without comorbidities that might affect their ability to heal. Type B hosts have 1 or more comorbidities that increase their risk of treatment failure, including local (eg, vascular disease, chronic edema, fibrosis from radiation or scarring, and obesity) and systemic factors (eg, drug use, age, diabetes mellitus, malignancy, immune deficiencies, and malnutrition).8 Type C hosts are compromised to the point that the benefits of treatment are outweighed by the possible risks. These patients are offered palliation or treated expectantly while their comorbidities are addressed.
The Cierny-Mader system identifies 4 anatomic types of osteomyelitis (Figure 1): medullary (type I), superficial (type II), localized (type III), and diffuse (type IV). Medullary disease involves the internal surface of the bone only, often associated with intramedullary hardware. Superficial osteomyelitis is often associated with soft tissue infections that spread down to bone, such as the base of an open pressure ulcer. Localized disease involves the full thickness of the cortex and is essentially a deep extension of a superficial process. These lesions are limited enough that surgical resection of involved bone leaves a stable segment. In contrast, diffuse osteomyelitis is a full-thickness infection extensive enough to require fixation following debridement due to instability.7 This classification system still guides treatment despite having a poor interobserver variability. It is often difficult to differentiate between a medullary and a superficial or localized infection. Magnetic resonance imaging often shows a diffuse appearance, which is a more accurate and realistic representation of the infectious process.
Figure 1: Cierny and Mader classification showing the 4 anatomic types of osteomyelitis known as medullary (A), superficial (B), localized (C), and diffuse (D).
Osteomyelitis can arise secondary to hematogenous spread or from a contiguous source of infection. Hematogenous infection is more common in those younger than 20 years and older than 60 years and is the least common form of the disease. It rarely causes osteomyelitis of the long bones in adults.9 Contiguous spread of infection can be caused by surgery, particularly the placement of prostheses or hardware, and trauma or other foreign body introduction. Osteomyelitis can also arise secondary to vascular insufficiency, commonly from a soft tissue infection in patients with diabetes mellitus.
In the hematogenous form, a single pathogen is usually isolated, with the most common organism being Staphylococcus aureus.10 In contrast, osteomyelitis secondary to contiguous spread or direct inoculation is usually caused by multiple organisms. Polymicrobial infection was responsible for approximately 30% of infections in one series.11Staphylococcus aureus is the most common isolate in polymicrobial infections, but anaerobes and gram-negative bacilli are also isolated. Antimicrobial-resistant organisms have become more common, and a recent study of approximately 200 patients noted that no single antibiotic regimen would adequately treat the infections.11 Rarely, tuberculosis, other atypical mycobacterium, and fungi may also cause osteomyelitis.
At the onset of infection in osteomyelitis, immediate vascular changes occur that compromise blood flow to the bone. If the infection is not eradicated before the bone dies, a sequestrum develops and provides a base for the formation of a microbial biofilm. Biofilms are comprised of exopolysaccharide polymers forming a protective fibrous matrix around host cells, as well as bacteria.12 Necrotic bone is resorbed, with cancellous bone requiring a few weeks to disappear. Cortical bone may take longer, even up to months, to erode. Inflammatory cells in granulation tissue are responsible for the destruction of infected bone. Microorganisms freely propagate, and the biofilm expands within the cavity formed by this resorption. As osteomyelitis progresses, new bone forms around the sequestrum from the neighboring pieces of intact periosteum and endosteum. As it begins to surround the area of infection, it is known as the involucrum. The involucrum is often irregular with perforating sinus tracts and may increase in density and thickness with time.13
Diagnosis is based on clinical examination, tissue cultures, laboratory studies, and imaging. Symptoms of chronic osteomyelitis are not always obvious and may include low-grade fever and chronic pain. Swelling, skin changes, and drainage over the site may be present. Acute infection in adults and particularly children may present with more systemic signs, such as chills, night sweats, erythema, and severe pain.13 Sinus tracts are often present over the area of chronically infected bone. If these become obstructed, they may form abscesses.
Initial workup should include basic complete blood count, inflammatory markers, cultures, and gram stain. Gram stain is a reflexive addition to any workup but may not lend any diagnostic value except to potentially guide early tailoring of antibiotic therapy. Cultures are necessary to identify the microbial offender responsible for the infection. Bone biopsies should be taken at the time of surgical debridement and should be carefully evaluated for sensitivities. Cultures taken from sinus tract drainage are not reliable for determining the microorganism responsible for deep infection.14 Cierny8 recommended using polymerase chain reaction DNA pyrosequencing to detect and characterize microorganisms. Prolonged culture (up to 14 days) has also been recommended to increased sensitivity for low-virulence organisms because 7-day cultures only provided evidence of infection in 64% of patients in a recent series.11
Surprisingly, leukocyte count may be normal; however, elevated erythrocyte sedimentation rate and noncardiac C-reactive protein are key signs of infection. The erythrocyte sedimentation rate and C-reactive protein will both decrease with successful treatment; therefore, their values should be followed closely during the pre- and postoperative phases. C-reactive protein is known to increase and decrease faster in response to physiologic changes than erythrocyte sedimentation rate. In addition to inflammatory markers, laboratory studies, including albumin, prealbumin, creatinine, and blood glucose should be followed to ensure optimization of host factors.10 Blood cultures are positive only in the acute hematogenous form of osteomyelitis and generally do not assist with the diagnosis of chronic infection in long bones.1
Common imaging techniques for detecting osteomyelitis include plain radiography (Figure 2), computed tomography, magnetic resonance imaging, and radionuclide labeled scans (Figure 3). Often, more than 1 type of imaging is needed for adequate diagnosis and surgical planning. Radiographic changes are visible approximately 2 weeks after the physiologic process of infection begins. The classic signs on plain radiographs include periosteal reaction and osteopenia.10 As the infection progresses, radiographic signs (in order of appearance) are soft tissue swelling, solid periostitis, lysis and lucencies, surrounding sclerosis, and sinus tracts.15
Figure 2: Anteroposterior (A) and lateral (B) radiographs of a distal femur highlighting the features of diffuse osteomyelitis, which include regional osteopenia, periosteal reaction with aggressive features (including Codman’s triangle), peripheral sclerosis, sequestrum, and involucrum.
Figure 3: Features of diffuse tibial osteomyelitis as shown on coronal T1- (A) and T2-weighted (B) magnetic resonance images. Axial computed tomography scan revealing diffuse proximal femoral osteomyelitis (C) and axial magnetic resonance image showing type II osteomyelitis of the tibia (D).
Computed tomography scan can assist in visualizing soft tissue changes surrounding a bony infection but is impractical to use for infections with local hardware due to resultant artifact. It is best used for detailed surgical planning because it clearly identifies sequestra and devascularized bone. Magnetic resonance imaging offers higher resolution and easily differentiates between bone and soft tissue involvement. It has high sensitivity and specificity for diagnosing osteomyelitis, which typically appears as a decreased local marrow signal on T1 and an increased local marrow signal on T2.16 Sinus tracts are also well visualized on magnetic resonance imaging but often require gadolinium enhancement.15
Radionuclide labeled scans are useful, especially in clinical situations where a clear diagnosis has not been made and in acute settings when radiographs are not helpful. However, they do not offer high-resolution delineation of anatomical involvement. Bone scans with methylene diphosphonate are highly sensitive and specific for osteomyelitis when increased activity is seen on initial and delayed images but becomes less accurate in the setting of recent surgery or trauma. White blood cell labeled scans may be performed with several different labels and require longer testing time but offer improved specificity.15 Gallium citrate and indium may also be used as labeling compounds to identify areas of inflammation but are less popular due to cost and technical requirements.10
Definitive management of long bone osteomyelitis requires a multidisciplinary approach involving aggressive surgical debridement and reconstruction followed by antibiotic therapy.10 Antibiotic therapy alone leads to high failure rates. The current authors believe that osteomyelitis should be surgically treated as a malignancy, with wide clear margins ensuring adequate soft tissue coverage. High recurrence rates are seen with conservative debridement.1 Soft tissue coverage and dead space management after extensive debridement is paramount because spaces left unmanaged may contribute to ongoing infection. All efforts should be made to optimize the host prior to treatment, such as smoking cessation and close control of blood glucose in patients with diabetes mellitus.9
Tradition has dictated that antibiotic therapy should last 4 to 6 weeks, based largely on animal studies and the knowledge that it takes approximately 4 weeks for bone to revascularize after surgical debridement.10 Haidar et al17 proposed that a shorter duration of antibiotic treatment could be feasible following aggressive surgical debridement and well-vascularized flap placement. Antibiotic therapy alone fails because the infection site has a poor vascular supply. Without adequate blood flow to the area, adequate concentrations of antimicrobials cannot be attained. Levels of antibiotics in bone are less than 20% of serum levels, even in healthy bone,1 and are theoretically even lower in diseased tissue. The biofilms formed in osteomyelitis may further decrease the penetration of antimicrobials.
Once adequate surgical debridement has occurred, both the offending biofilm and the vascular deficiency should have been addressed, and intravenous antibiotics should be effective. Shorter courses of intravenous antibiotics would save the health care system a significant amount of money considering the cost and logistical barriers to outpatient intravenous therapy. A recent Cochrane review attempted to summarize the evidence for systemic antibiotic treatment after surgical debridement for chronic osteomyelitis.6 The authors found few quality studies, but those chosen demonstrated no significant difference between recurrence rates 12 months after oral and parenteral antibiotic treatment.6
Antibiotics can also be delivered locally rather than systemically. Alternate routes of antibiotic delivery include antibiotic-impregnated cement beads, which provide both high local antibiotic concentrations and dead space management. The effectiveness of this treatment, both alone and in conjunction with intravenous antibiotics, has been demonstrated in animal models and human trials.17 However, local antibiotic strategies have not been proven superior to intravenous administration and require surgical removal.
Biodegradable antibiotic delivery systems obviate the need for a second surgical procedure for removal and several systems are being developed. Collagen fleece is a nontoxic, biocompatible antibiotic carrier that offers a triphasic antibiotic release and strong clinical results to date. Polyesters are another alternative for biodegradable delivery, offering a slower breakdown and some evidence of intracellular action. Calcium-based carriers, including Plaster of Paris, calcium sulphate, and calcium hydroxyapatite, are promising because they allow tissue and bone ingrowth as they degrade. Other potential delivery systems not requiring surgical removal are polyanhydrides, amylose starch, and composite carriers.
The extent of surgical debridement should be planned to account for the host type, area of involvement, and likely need for soft tissue coverage and stabilization. Adequate debridement is the key to treatment success, and all dead and ischemic tissues and sinus tracts should be removed.7 Simpson et al18 prospectively studied the effect of extent of surgical debridement on cure rates and found 100% cure rates with wide excision and 100% recurrence rates with intralesional biopsy and local debulking. Marginal resection with less than 5-mm margins exhibited a 28% recurrence rate, all of which were found in type B hosts.18
When debriding, healthy bleeding tissue should be visualized at all boundaries of the surgical site, followed by thorough irrigation.19 At this point, the need for stabilization and soft tissue coverage can be assessed. Stage I infections limited to the medullary canal may be treated with intramedullary reaming and occasionally very localized unroofing and curettage.7 If evidence exists of metaphyseal involvement or endosteal scalloping, a longitudinal trough should be made to access the canal for curettage, which minimizes effects on bony stability.20 Primary closure can usually be attained because the dead space is limited to the intramedullary canal.8 Stage II infections can be addressed with soft tissue debridement and decortication of the bone adjacent to the infection. Coverage with a flap has been described both simultaneously and during a second-stage procedure,7 either with local or free flap mobilization. Stage III osteomyelitis usually requires debridement of soft tissue, sequestrum, and cortex, as well as decompression of the involved medullary canal. Cierny et al7 referred to this process as saucerization, alluding to the shape of the bone left untouched. Stabilization, soft tissue coverage, and grafting may all be necessary depending on the extent of involvement, with more than 70% of the cortex required for absolute stability.20 Stage IV infections are the most challenging to treat surgically because they most often require multiple staged procedures and necessitate osseous stabilization. Staged procedures address the need for eradication of infection followed by osseous reconstruction aiming for union and stability once the tissue is healthy. In Figure 4, the current authors present their treatment algorithm.
Figure 4: Algorithm of the authors’ preferred treatment methodology for the management of stage 4 osteomyelitis.
For extensive involvement with significant segmental bone loss, several methods of staged treatment have been described, with no current consensus on a gold standard. A wide variety of studies exist, with many combinations of early and late stabilization, coverage, structural support, and antibiotic delivery. Some weaknesses in the literature include a paucity of long-term follow-up data and a lack of a universal definition of cure.
The Papineau, or open air, technique and its various permutations have been widely cited in the treatment of osteomyelitis. This method involves radical debridement, staged bone grafting, and delayed soft tissue coverage with either natural granulation or skin grafting.21 This technique is often used in type III infections following saucerization because the bone graft does not offer significant structural support.22 Meticulous wound care is needed because the debrided area is left open with the bone graft exposed. This technique has somewhat fallen out of favor in light of newer plastic surgery techniques for tissue transfer and grafting but remains a foundational approach to the surgical treatment of osteomyelitis.
McNally et al23 first described a staged procedure, known as the Belfast technique, comprised of radical debridement, early soft tissue coverage (with or without antibiotic beads) to eliminate dead space, and delayed bone grafting, if necessary. This decreased the hospitalization time necessary for treatment compared with previous methods and led to a cure rate of 92%. They emphasized wide resection of infected areas with no attempt to salvage diseased tissue as a key component of treatment.23
The Ilizarov technique involves placing a circular external fixation device for the long-term treatment of bone defects. It is both time- and cost-intensive but has had success in the treatment of osteomyelitis. Marsh et al24 reported a 100% cure rate at 1-year follow-up using an Ilizarov frame on infected long bones, although 3 patients failed to unite their fractures in this time. This technique allows stabilization with concurrent soft tissue treatment as well as distraction osteogenesis to close a segmental gap and can be combined with other forms of treatment for optimal outcomes.
Vacuum-assisted closure of soft tissue defects has been used in many settings, and recent evidence has demonstrated its efficacy in the treatment of stage II, III, and IV infections after debridement and the initiation of antibiotic therapy. One study compared vacuum-assisted closure therapy to conventional wound care and found a significant reduction in infection recurrence, the rate of necessary subsequent flap treatment, and the incidence of positive cultures after treatment completion.25 Vacuum-assisted closure therapy has also been implemented in combination with the Papineau technique in lieu of wet-to-dry dressings with good results.26
Masquelet pioneered a technique for the treatment of segmental bony defects involving initial wide debridement and the placement of an antibiotic-loaded cement spacer with temporary stabilization with intramedullary nailing, plating, or external fixation. This is followed 8 weeks later by removal of the spacer and careful placement of autograft into the induced membrane rich in growth factors (Figures 5–7).27 However, this technique has not been specifically studied in the treatment of osteomyelitis.
Figure 5: Photographs showing the first stage of the Masquelet technique used to excise a large segment of the affected tibia. The skin is marked based on magnetic resonance imaging findings and extension of the infectious process (A). Photograph showing the application of a monotube external fixator and resection of the affected segment with clear margins on the intraoperative frozen section (B). Fluoroscopic imaging showing the affected bony segment resection (C, D).
Figure 6: Clinical photograph of the tibial segment affected by the infection that has been cut in half to show the involvement of both the cortex and the medullary cavity (A). Clinical photograph showing that the sinus tract is clearly visible. Anteroposterior (C) and lateral (D) radiographs of the tibia with the cement spacer in situ.
Figure 7: Anteroposterior (A) and lateral (B) radiographs of the tibia following the second stage of reconstruction using Masquelet technique. The bone graft (30 mL) was harvested using a reamer-irrigator-aspirator from the ipsilateral femur and inserted into the defect after removal of the antibiotic spacer.
For infections that persist despite debridement and antibiotics, the Lautenbach technique has been offered as an alternative treatment. This procedure was first described in patients with total hip arthroplasty infections and involves intramedullary reaming and placement of a closed endosteal irrigation system.28 This system allows for the local delivery of antibiotics and continuous sampling of the infected cavity for cultures and narrowing of antibiotic therapy. Hashmi et al29 reported using this technique in 17 patients with chronic osteomyelitis. Therapy was continued until 3 consecutive negative cultures were obtained and the endosteal cavity was filled with granulation tissue, with a mean treatment length of 27 days. They reported only 1 recurrence, which resolved with repeat treatment.29
Beals and Richard30 compared the treatment of chronic osteomyelitis of the tibia with antibiotics and one of several surgical techniques by the same surgeon. They found good results with debridement and muscle flap, bone graft, bone transport, the Papineau technique, and an Ilizarov frame. Twenty-seven of 30 patients had good outcomes, suggesting that optimal results can be obtained with any well-planned surgical procedure.31
A plethora of reconstructive techniques exist, none of which has been proven superior in the setting of osteomyelitis, but the key remains eradication of infection with wide resection and adjuvant antibiotics. Failure of infection elimination appears to be directly related to the extent of resection.18 The philosophy guiding the management of long bone osteomyelitis should be early aggressive management along with optimization of the host medical and nutritional status, with a focus on wide margins excision and debridement of all affected tissues. Necessary length of antibiotic treatment is still debatable; however, increasing rates of resistance underscore the importance of accurate cultures and targeted therapy. New methods for soft tissue coverage and bony reconstruction continue to be introduced, and it is important to refer patients to centers specialized in bone infection. An algorithm, such as the one suggested here (Figure 4), should be used to guide management. Future research should ideally address the lack of prospective, controlled, randomized trials comparing techniques and identify a gold standard of treatment for antibiotic length and delivery.
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- Perry CR. A historical perspective. In: Bone and Joint Infections. London: Martin Dunitz; 1996:1–8.
- Klenerman L. A history of osteomyelitis from the Journal of Bone Joint Surg. 1948–2006. J Bone Joint Surg Br. 2007; 89:667–670.
- Schenker ML, Yannascoli S, Baldwin KD, Ahn J, Mehta S. Does timing to operative debridement affect infectious complications in open long bone fractures? A systematic review. J Bone Joint Surg Am. 2012; 94:1057–1064 doi:10.2106/JBJS.K.00582 [CrossRef] .
- Penn-Barwell JG, Bennett PM, Fries CA, Kendrew JM, Midwinter MJ, Rickard RF. Severe open tibial fractures in combat trauma: management and preliminary outcomes. Bone Joint J. 2013; 95:101–105 doi:10.1302/0301-620X.95B1.30580 [CrossRef] .
- Conterno LO, da Silva Filho CR. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev. 2009; 3:1–30.
- Cierny G, Mader JT, Penninck JJ. A clinical staging for adult osteomyelitis. Clin Orthop Relat Res.2003; (414):7–24 doi:10.1097/01.blo.0000088564.81746.62 [CrossRef] .
- Cierny G. Surgical treatment of osteomyelitis. Plast Reconstr Surg. 2011; 127:190S–204S doi:10.1097/PRS.0b013e3182025070 [CrossRef] .
- Mader JT, Calhoun JH, Lazzarini L. Adult long bone osteomyelitis. In: Calhoun JH, Mader JT, eds. Musculoskeletal Infections. New York, NY: Marcel Dekker; 2003:149–182.
- Lazzarini L, Mader JT, Calhoun JH. Osteomyelitis in long bones. J Bone Joint Surg Am. 2004; 86:2305–2318.
- Sheehy SH, Atkins BA, Bejon P, et al. The microbiology of chronic osteomyelitis: prevalence of resistance to common empirical antimicrobial regimens. J Infect. 2010; 60:338–343 doi:10.1016/j.jinf.2010.03.006 [CrossRef] .
- Gristina AG, Oga M, Webb LX, Hobgood CD. Adherent bacterial colonization in the pathogenesis of osteomyelitis. Science. 1985; 228:990–993 doi:10.1126/science.4001933 [CrossRef] .
- Calhoun JH, Manring MM, Shirtliff M. Osteomyelitis of the long bones. Semin Plast Surg. 2009; 23(2):59–72 doi:10.1055/s-0029-1214158 [CrossRef] .
- 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 pre-operative assessment of osteomyelitis. J Bone Joint Surg Am. 1991; 73:745–749.
- Pineda C, Vargas A, Rodriguez AV. Imaging of osteomyelitis: current concepts. Infect Dis Clinic N Am. 2006; 20:789–825 doi:10.1016/j.idc.2006.09.009 [CrossRef] .
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- Haidar R, Boghossian AD, Atiyeh B. Duration of post-surgical antibiotics in chronic osteomyelitis: empiric or evidence-based?Int J Inf Dis. 2010; 14:e752–e758 doi:10.1016/j.ijid.2010.01.005 [CrossRef] .
- Simpson AH, Deakin M, Lathan JM. The effect of the extent of surgical resection on infection-free survival. J Bone Joint Surg Br. 2001; 83:403–407 doi:10.1302/0301-620X.83B3.10727 [CrossRef] .
- Forsberg JA, Potter BK, Cierny G, Webb L. Diagnosis and management of chronic infection. J Am Acad Orthop Surg. 2011; 19:S9–S19.
- Parsons B, Strauss E. Surgical management of chronic osteomyelitis. Am J Surg. 2004; 188:S57–S66 doi:10.1016/S0002-9610(03)00292-7 [CrossRef] .
- Papineau LJ. Excision-graft with deliberately delayed closing in chronic osteomyelitis [in French]. Nouv Presse Med. 1973; 2:2753–2755.
- Papineau LJ, Allfageme A, Dalcourt JP, Pilon L. Chronic osteomyelitis: open excision and grafting after saucerisation. Int Orthop. 1979; 3:165–176.
- McNally MA, Small JO, Tofighi HG, Mollan RAB. Two-stage management of chronic osteomyelitis of the long bones. J Bone Joint Surg Br. 1993; 75:375–380.
- Marsh DR, Shah S, Elliott J, Kurdy N. The Ilizarov method in nonunion, malunion, and infection of fractures. J Bone Joint Surg Br. 1997; 79:273–279 doi:10.1302/0301-620X.79B2.6636 [CrossRef] .
- Tan Y, Wang X, Li H, Zheng Q, Li J, Feng G, Pan Z. The clinical efficacy of the vacuum-assisted closure therapy in the management of adult osteomyelitis. Arch Orthop Trauma Surg. 2011; 131:255–259 doi:10.1007/s00402-010-1197-x [CrossRef] .
- Archdeacon MT, Messerschmitt P. Modern Papineau technique with vacuum-assisted closure. J Orthop Trauma. 2006; 20:134–137 doi:10.1097/01.bot.0000184147.82824.7c [CrossRef] .
- Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet AC. Treatment of posttraumatic bone defects by the induced membrane technique. Orthop Traum Surg Res. 2012; 98:97–102 doi:10.1016/j.otsr.2011.11.001 [CrossRef] .
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- Hashmi MA, Norman P, Saleh M. The management of chronic osteomyelitis using the Lautenbach method. J Bone Joint Surg Br. 2004; 86:269–275 doi:10.1302/0301-620X.86B2.14011 [CrossRef] .
- Beals RK, Richard EB. The treatment of chronic open osteomyelitis of the tibia in adults. Clin O rthop Relat Res. 2005; (433):212–217 doi:10.1097/01.blo.0000150462.41498.fe [CrossRef] .