Skip to main content
  • Systematic Review
  • Open access
  • Published:

Single versus two-stage management of long-bone chronic osteomyelitis in adults: a systematic review and meta-analysis



Chronic osteomyelitis is a debilitating bone infection, characterized by a persistent infection over months to years, poses diagnostic and therapeutic challenges due to its insidious nature and potential for severe bone and soft tissue destruction. This systematic review and meta-analysis aims to review the literature on the treatment of chronic osteomyelitis in long bones and assess cure rates in single versus two-stage surgery.


Following the PRISMA guidelines and registered with PROSPERO (ID: CRD42021231237), this review included studies that reported on the management of chronic osteomyelitis in long bones using either a planned one-stage or two-stage surgical approach in adult patients. Databases searched included Medline, Embase, Web of Science, CINAHL, HMIC, and AMED, using keywords related to osteomyelitis, long bones, and surgical management. Eligibility criteria focused on adults with chronic osteomyelitis in long bones, with outcomes reported after a minimum follow-up of 12 months. The meta-analysis utilized the random-effects model to pool cure rates.


The analysis included 42 studies with a total of 1605 patients. The overall pooled cure rate was 91% (CI 95%) with no significant difference observed between single-stage and two-stage surgeries (X2 = 0.76, P > 0.05). Complications were reported in 26.6% of cases in single-stage procedures and 27.6% in two-stage procedures, with prolonged wound drainage noted as a common issue. Dead space management techniques varied across studies, with antibiotic-loaded calcium sulphate beads used in 30.4% of cases.


This meta-analysis reveals no significant difference in cure rates between single and two-stage surgical treatments for chronic osteomyelitis in long bones, supporting the efficacy of both approaches. The current treatment strategy should include a combination of debridement, dead space management using local and systematic antibiotics and soft tissue reconstruction if necessary.


Osteomyelitis is characterized by an infectious and destructive inflammatory process affecting the bone that stems from microorganisms' invasion. The infection's etiology varies, originating either from local spread linked to trauma and surgery or from hematogenous dissemination, particularly in the elderly and children [1, 2]. The disease is often compounded by immune, vascular, and soft tissue problems [2]. The manifestations of chronic osteomyelitis are diverse, often remaining indolent for months before symptoms become apparent. The distinction between acute and chronic osteomyelitis, however, is contentious [3]. While some define chronicity based on histopathological examination and sequestrum formation, others consider it chronic when the infection persists for months to years, an arbitrary but commonly used timeframe [1,2,3,4]. Nevertheless, chronic osteomyelitis evolves over an extended period, potentially leading to sequestrum, bone destruction, marrow infection, soft tissue involvement, and fistulous tracts [4]. The severity can vary widely, from simple, manageable infections to severe cases with extensive bone destruction, significant functional deficit and even limb loss.

The management of osteomyelitis requires a multifaceted and aggressive approach to eradicate the infection and optimize outcomes [5,6,7]. Treatment modalities vary, and decision-making remains challenging as it encompasses various surgical techniques, antibiotic delivery methods, duration of antibiotic treatment, and surgical staging [7]. The problems the patient may encounter are multifaceted, and has been highlighted in the classification by Cierny and Mader et al., which categorizes osteomyelitis based on anatomical location, physiological status, and high-risk factors [8]. The complexity of treating osteomyelitis depends on its location, often involving long-term and debilitating treatment regimens. Success is typically indicated by a prolonged remission period, but conclusively declaring the disease cured is often problematic due to late recurrence.

Traditionally, treatment has relied on prolonged antibiotic use and multiple surgical debridements. In two-stage procedures, the primary focus is on eliminating the infection through bone and soft tissue resection, followed by stabilization of the bone, often externally, using fixators or frames. A second stage is planned approximately 4–8 weeks later, though this period can vary. This stage occurs after a course of antibiotics and once the infection has resolved both clinically and biochemically. The second stage concentrates on restoring function, utilizing techniques like fibular grafts, the Masquelet technique, autologous cancellous bone grafts, or bone transport [9,10,11]. Conversely, single-stage techniques aim to eradicate the infection with appropriate debridement and both local and systemic antibiotics, managing the bone defect in the same stage using techniques similar to those used in the second stage of two-stage management [12,13,14].

Current approaches emphasize a single thorough debridement, effective management of dead space, both local and systemic antibiotic administration, and a multidisciplinary strategy [15,16,17].

Comparisons between these techniques in the literature are scarce. This systematic review and meta-analysis aim to thoroughly review the literature on the treatment of chronic osteomyelitis in long bones and assess cure rates in single versus two-stage surgery for the condition.


The search and selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered with PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021231237).

Search strategy

A systematic search of Medline, Embase, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Healthcare Management Information Consortium (HMIC) and the Allied and Complementary Medicine (AMED) databases was performed using the following search strategy: (("osteomyelitis"[Title/Abstract] OR "bone infection"[Title/Abstract]) AND ("humerus"[Title/Abstract] OR "ulna"[Title/Abstract] OR "radius"[Title/Abstract] OR "fibula"[Title/Abstract] OR "single stage"[Title/Abstract] OR "one stage"[Title/Abstract] OR "two stage"[Title/Abstract] OR "two-stage"[Title/Abstract] OR "long bone"[Title/Abstract] OR "femur"[Title/Abstract] OR "tibia"[Title/Abstract])). Finally, reference lists of relevant articles were reviewed to identify additional articles that were potentially missed during the initial search.

Eligibility criteria

Studies that met the following criteria were included: (1) Management of chronic osteomyelitis in long bones using a planned one-stage or planned two-stage, 2) Patients aged 18 or older, 3) Follow up of at least 12 months, and 4) Clinical outcomes were reported.

Studies were excluded if they met any of the following criteria: (1) Review articles; (2) full text not available; (3) cadaveric studies; (4) Patients less than 18 years; (5) treatment of septic or infected non-unions, (6), non-bacterial osteomyelitis, (7) case series with fewer than 10 patients, (8) joint infections, (9) articles including non-long-bone osteomyelitis were excluded if they did not report outcome data separately for long bones. In addition, articles reporting outcomes on septic non-unions and osteomyelitis collectively were excluded.

Study screening

Titles and abstracts were independently screened for relevance by three authors using Covidence (AL, AE and MP) (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Potentially relevant articles underwent full-text screening, with any conflicts between the authors being resolved by discussion and consensus with the senior authors (HS).

Quality assessment and risk of bias

Study quality assessment was conducted using the methodological index for non-randomized studies (MINORS) tool. Methodological quality was categorized prior as follows: a score of 0–8 or 0–12 was considered poor quality, 9–12 or 13–18 was considered fair quality, and 13–16 or 19–24 was considered excellent quality, for non-comparative and comparative studies, respectively. For randomized controlled trials, the Cochrane risk of bias-2 (RoB-2) tool was used to assess study quality. Quality assessment measurements are denoted after each study in Table 1.

Table 1 Baseline demographics and patient characteristics

Data extraction

Three authors independently extracted relevant data from the included studies to a previously piloted Microsoft Excel spreadsheet (Microsoft, Redmond, Washington, USA). These data included general article information, patient demographic and surgical procedure details, and relevant outcome measures.


Outcomes included the cure rate (%). A meta-analysis of proportions using the random-effects model was used to pool the cure rate (%) estimates from different studies. Without appropriate data transformation, the accompanying meta-analyses experience threats to statistical conclusion validity [18], such as confidence limits falling outside of the established zero-to-one range and variance instability [19]. While the logit transformation solves the problem of confidence interval estimates falling outside the zero to one range, it does not necessarily resolve the issues regarding variance from extreme proportional datasets. As the double arcsine transformation (Freeman-Tukey transformation) addresses both problems listed above, it is the preferred transformation method and was implemented in the current analysis. Once the meta-analysis had been performed on the transformed proportions, a back-transformation was performed. There is still no consensus about the back-transformation method that should be used with the Freeman-Tukey double arcsine method, although the harmonic mean was suggested for back-transformation [20]. Secondary outcomes included types of treatments used, complications, dead space management techniques, length of hospital stay, data on cost and the need for secondary interventions.


Statistical analysis was performed using R v 3.6.3 (R Core Team, Vienna, Austria). The random-effects model (using the maximum likelihood estimator for tau) was used to pool the effect sizes from the included studies. The underlying hypothesis for adopting the random-effects model is that heterogeneity or observed variance of effect is a sum of sampling error and variation in true-effect sizes stemming from inter-population variability. The generic inverse variance method was used to weigh each trial’s per-protocol population. Subgroup analysis was performed based on the stage. The overall proportion was calculated as well as the proportion within each subgroup. Forest plots were used to visualize the results. P values < 0.05 were considered statistically significant.

Prediction interval

The prediction interval was used to assess the treatment effect that may be predicted in future analyses, considering the different settings across different studies. It captures the variability in the true treatment effect across different settings. With substantial heterogeneity, prediction intervals will be broader than confidence intervals and might be considered a more conservative technique to integrate uncertainty in the analysis [21].

Sensitivity analysis

Sensitivity analysis was performed using the leave-one-out method to assess the effect of the different studies on the estimate and heterogeneity. Sensitivity analysis was performed to assess whether the pooled estimate and between-study heterogeneity were significantly affected by the exclusion of certain studies.

Publication bias and heterogeneity between studies

Funnel plots were used to assess publication bias. Egger’s test was used to test the asymmetry of funnel plots [22]. The trim-and-fill method was also used to detect and adjust for publication bias [23]. The I2 statistic was used to explore the percentage of heterogeneity attributed to variation in true-effect sizes secondary to inter-population variation. Estimates from subgroups within the same study were pooled using a fixed-effects model and used in the meta-analysis. The 95% confidence interval (CI) and Z-statistic were calculated and used for hypothesis testing. Heterogeneity between studies was quantified using the I2 statistic. In the case of high heterogeneity, the cause was investigated, the outlier was removed, and a new result was presented.


After the removal of duplicates from the initial search, a total of 3398 references were retrieved for title and abstract screening (Fig. 1). A total of 3237 articles were excluded after the initial title/abstract screening. Next, 161 studies underwent full-text review. A total of 42 studies were included in the final analysis.

Fig. 1
figure 1

PRISMA flowchart illustrating inclusion of studies into the review

Sample data

The pooled patient demographics are outlined in Table 1. Among the included studies, all but one were retrospective, encompassing both cohort and retrospective comparative studies. A total of 1605 patients were analyzed, predominantly male (77%), with an average age of 42.7 ± 8.5 years. The mean follow-up duration was 36 ± 18 months. The studies predominantly focused on one-stage management (28 studies), while twelve opted for planned two-stage management, and two studies offered comparisons between single and two-stage management.

Characteristics of osteomyelitis

The infection characteristics, host status, anatomical regions involved, and organisms are detailed in Table 2. The Cierny-Mader (CM) classification, reported in most studies, identified CM type III as the most common (60%) with host type B prevailing (51%). The etiology was primarily post-traumatic (64%, n = 812), followed by hematogenous origins (23%, n = 295). The tibia was the most affected site (57%, n = 819), with the femur (27%, n = 392) and humerus (6.8%, n = 98) following. Methicillin-susceptible Staphylococcus aureus (MSSA) was the predominant organism (28.5%, n = 357), with Methicillin-resistant Staphylococcus aureus (MRSA) found in 8.7% (109) of cases. Notably, 24.8% (n = 310) of cases showed no growth.

Table 2 Characteristics of the osteomyelitis according to classification, location and organisms

Management strategies

The surgical treatment strategies are categorized in Table 3, including debridement, dead space management, soft tissue coverage, bone graft, and osseous stabilization. Dead space management techniques varied, with antibiotic-loaded calcium sulphate (CaSO4) beads (e.g., Stimulan, Osteoset T) used in 30.4% (n = 469) of cases. Polymethyl methacrylate (PMMA) cement was utilized in 15% (n = 236) of cases, employed as beads, spacers, and in Masquelet techniques. Other treatments included Cerament G (CaSO4 + hydroxyapatite), S53P4 bioactive glass, and others as described in Table 3. Flaps were required in 21.6% (n = 332) of cases, and bone grafts were used in 17% (n = 274), incorporating autologous, allograft, and reamer aspirate autograft.

Table 3 Management strategies and cure rates within the included studies


Complications reported across studies exhibited considerable heterogeneity, detailed in Table 4. Recurrence of infection was treated as a failure, not a complication, and is thus analyzed separately under cure rates. The overall complication rates were similar for both single-stage and two-stage treatments (26.6% and 27.6%, respectively). The most frequent complication in single-stage procedures was prolonged wound drainage (13%), with stiffness and reduced range of motion also commonly reported.

Table 4 Aggregated complications in both groups

Meta-analysis of cure rates

The analysis included 1636 patients. Single stage method was used in 1339 patients and the two-stage method was used in 297 patients. The pooled cure rate was 91% (CI 87%; 93%). Stratifying the analysis by stage did not reveal a statistically significant difference (X2 = 0.76, P > 0.05) with similar cure rate across stages (Fig. 2). The funnel plot was symmetric indicating the absence of publication bias. Egger’s test was not statistically significant (P = 0.64).

Fig. 2
figure 2

Meta-analysis of cure rates in single and two-stage groups


In our systematic review and meta-analysis on the treatment of osteomyelitis, we examined the evolving therapeutic strategies for this complex condition. Our findings reveal that, in terms of cure rates, or more appropriately termed, non-recurrence rates, there appears to be no significant difference when comparing single versus two-stage management of chronic osteomyelitis. This analysis is the first to collectively assess the success rates of single versus two stage management.

The decision between single-stage and multi-stage procedures is important, particularly considering the implications of lengthier hospital stays, increased costs, and operational complexities associated with two-stage management. Zhou et al. highlighted the notably higher costs and extended hospital stays associated with two-stage procedures compared to single-stage management [12]. Their findings indicate an average hospital stay of 28 days for the two-stage group, versus 18 days for those undergoing single-stage procedures. Similar trends are noted in studies by McNally, Ueng, and Qiu, reporting hospital stays of 27, 22, and 24 days respectively in two-stage treatment [10, 24, 25]. However, variability in hospital stay lengths is influenced by different institutional protocols and the possibility of outpatient management. Across studies, a comprehensive report on the costs and durations of hospital stays is generally deficient.

The surgical aspect of treatment is intricate, and our data indicates that debridement alone is associated with lower cure rates. Quantifying the extent of debridement in various studies presents another challenge, as the terminology used to describe it, such as "radical" or "adequate," is open to diverse interpretations. Consequently, the current data does not allow for distinct categorization of debridement methods.

Dead space management has become increasingly significant in recent years. Techniques such as antibiotic-coated beads and cement, muscle flaps, and bone grafts for addressing compromised soft tissue and bone loss have shown favorable outcomes based studies included in this review.. The induced membrane or Masquelet technique, though requiring a two-stage approach, has shown reliable results in our review [10, 11]. Additionally, bone defect management techniques, such as circular frames and bone segment transfers, offer stability, enabling early range of motion and weight-bearing. Jagadeesh et al.'s study reported a higher success rate with the use of calcium sulfate compared to debridement alone [13]. The current evidence suggests that the effectiveness of various local antibiotic delivery systems is comparable [14, 26].

Complication reporting varied across studies, with a notable incidence of prolonged wound drainage in single-stage procedures, often associated with calcium sulfate beads. While concerning, this drainage is not necessarily a harbinger of infection. Ferguson et al. reported high rates of wound leakage using calcium sulphate beads, but highlighted the low risk of infection associated with it [14]. Jagadeesh et al. also reported 18 out of 50 patients had ongoing serous discharge with the use of calcium sulphate that lasted up to 4 weeks resolving without treatment other than dressing changes [13]. This is in line with reports of 4–30% serous discharge while calcium sulphate is undergoing resorption. It is perhaps mitigated by adequate soft tissue coverage and judicious use of calcium sulphate [12, 14, 27, 28]

Commonly reported complications included wound issues, stiffness, and neuropathic symptoms, which could potentially be alleviated by early rehabilitation following extensive surgeries. Moreover, data on postoperative range of motion is scarce; improved reporting could reveal differences in single-stage groups, potentially allowing for earlier postoperative rehabilitation. More pin site issues were observed in the two-stage group, potentially due to longer durations of fixator use [10, 12, 29]. However, drawing definitive conclusions in this regard is difficult due to the more frequent use of fixators in two-stage management, as well as variations in the definition of pin-site infections. The occurrence of fractures in both treatment approaches necessitates cautious management, particularly regarding the introduction of implants. Systemic complications such as deep vein thrombosis, pulmonary embolism, and acute kidney injuries were also noted, albeit less frequently.

Perhaps it is key to highlight the literature's deficiencies, including the heterogeneity in antibiotic administration, inclusion criteria covering various bones and etiologies, and diverse causative organisms. These variations make it challenging to conclusively determine the superiority of specific treatments. In addition, the analysis represents single-arm comparisons, which are potential sources of bias. Although studies utilized similar techniques for both single and two-stage procedures, certain factors, such as the degree of osteomyelitis and the patient's physiological status, may indicate the use of one technique over the other. Another point of interest would be an analysis of the potential complications in both treatment groups. However, the variation in definitions of complications and the lack of clear reporting of complications arising due to disease and treatment did not allow for an accurate analysis in this regard.

Future research should focus on prospective studies, examining variables like causative organisms, patient demographics, Cierny-Mader classification, and specific treatment modalities. In addition, it will be helpful to know whether major differences exist between different preparations of antibiotic coated beads.


Chronic osteomyelitis is a complex condition with various treatments and interventions described. The data from our analysis suggests that single and two-stage treatment of chronic osteomyelitis yields comparably effective results. The current treatment strategies included a combination of debridement, dead space management, local and systematic antibiotics along with bone stabilization and soft tissue reconstruction if necessary. However, the indications for using either technique may play a role in predicting success rates. Higher-level studies should be conducted to provide more generalizable conclusions.


  1. Klenerman L. A history of osteomyelitis from the Journal of Bone and Joint Surgery. J Bone Joint Surg Br. 2007;89:667–70.

    Article  CAS  PubMed  Google Scholar 

  2. Lew DP, Waldvogel FA. Osteomyelitis. The Lancet. 2004;364:369–79.

    Article  CAS  Google Scholar 

  3. Forsberg JA, Potter BK, Cierny G, Webb L. Diagnosis and management of chronic infection. Am Acad Orthopaed Surg. 2011;19:S8-19.

    Article  Google Scholar 

  4. Hatzenbuehler J, Pulling TJ. Diagnosis and management of osteomyelitis. Am Fam Phys. 2011;84:1027–33.

    Google Scholar 

  5. Panteli M, Giannoudis PV. Chronic osteomyelitis: what the surgeon needs to know. EFORT Open Rev. 2016;1:128–35.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pollak AN, Jones AL, Castillo RC, Bosse MJ, MacKenzie EJ. The relationship between time to surgical débridement and incidence of infection after open high-energy lower extremity trauma. J Bone Jt Surg-Am. 2010;92:7–15.

    Article  Google Scholar 

  7. Maffulli N, Papalia R, Zampogna B, Torre G, Albo E, Denaro V. The management of osteomyelitis in the adult. The Surgeon. 2016;14:345–60.

    Article  CAS  PubMed  Google Scholar 

  8. Cierny G, Mader JT, Penninck JJ. The classic: a clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003;414:7–24.

    Article  Google Scholar 

  9. Yu X, Wu H, Li J, Xie Z. Antibiotic cement-coated locking plate as a temporary internal fixator for femoral osteomyelitis defects. Int Orthop. 2017;41:1851–7.

    Article  PubMed  Google Scholar 

  10. Qiu X, Chen Y, Qi X, Shi H, Wang J, Xiong J. Outcomes of cement beads and cement spacers in the treatment of bone defects associated with post-traumatic osteomyelitis. BMC Musculoskelet Disord. 2017;18:256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wu H, Shen J, Yu X, Fu J, Yu S, Sun D, et al. Two stage management of Cierny-Mader type IV chronic osteomyelitis of the long bones. Injury. 2017;48:511–8.

    Article  PubMed  Google Scholar 

  12. Zhou C-H, Ren Y, Song H-J, Ali AA, Meng X-Q, Xu L, et al. One-stage debridement and bone transport versus first-stage debridement and second-stage bone transport for the management of lower limb post-traumatic osteomyelitis. J Orthop Transl. 2021;28:21–7.

    Article  Google Scholar 

  13. Jagadeesh N, Abdul A, Shivalingappa VM, Kumar H. Prospective comparative analysis of efficacy of local debridement with or without vancomycin impregnated calcium sulphate in chronic osteomyelitis. J Orthop. 2022;32:133–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ferguson J, Bourget-Murray J, Stubbs D, McNally M, Hotchen AJ. A comparison of clinical and radiological outcomes between two different biodegradable local antibiotic carriers used in the single-stage surgical management of long bone osteomyelitis. Bone Jt Res. 2023;12:412–22.

    Article  Google Scholar 

  15. Sambri A, Fiore M, Tedeschi S, De Paolis M. The need for multidisciplinarity in modern medicine: an insight into orthopaedic infections. Microorganisms. 2022;10:756.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ziran BH, Rao N, Hall RA. A dedicated team approach enhances outcomes of osteomyelitis treatment. Clin Orthop Relat Res. 2003;414:31–6.

    Article  Google Scholar 

  17. Pincher B, Fenton C, Jeyapalan R, Barlow G, Sharma HK. A systematic review of the single-stage treatment of chronic osteomyelitis. J Orthop Surg Res. 2019;14:393.

    Article  PubMed  PubMed Central  Google Scholar 

  18. García-Pérez MA. Statistical conclusion validity: Some common threats and simple remedies. Front Psychol. 2012;3:1.

    Article  Google Scholar 

  19. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health. 1978;2013(67):974–8.

    Article  Google Scholar 

  20. Dekkers OM, Egger M, Altman DG, Vandenbroucke JP. Distinguishing case series from cohort studies. Ann Intern Med. 2012;156:37–40.

    Article  PubMed  Google Scholar 

  21. Barker TH, Migliavaca CB, Stein C, Colpani V, Falavigna M, Aromataris E, et al. Conducting proportional meta-analysis in different types of systematic reviews: a guide for synthesisers of evidence. BMC Med Res Methodol. 2021;21:1.

    Article  Google Scholar 

  22. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Br Med J. 1997;315:629–34.

    Article  CAS  Google Scholar 

  23. Duval S, Tweedie R. A nonparametric, “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000;95:89.

    Article  Google Scholar 

  24. McNally MA, Ferguson JY, Scarborough M, Ramsden A, Stubbs DA, Atkins BL. Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier. Bone Joint J. 2022;104:1095–100.

    Article  PubMed  Google Scholar 

  25. Ueng WN, Shih CH. Semi open cancellous bone grafting. A 2 step method for closing small infected tibial bone defects. Clin Orthop Relat Res. 1994;306:175–82.

    Google Scholar 

  26. Ferrando A, Part J, Baeza J. Treatment of cavitary bone defects in chronic osteomyelitis: bioactive glass S53P4 vs. calcium sulphate antibiotic beads. J Bone Jt Infect. 2017;2:194–201.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhou C-H, Ren Y, Ali A, Meng X-Q, Zhang H-A, Fang J, et al. Single-stage treatment of chronic localized tibial osteomyelitis with local debridement and antibiotic-loaded calcium sulfate implantation: a retrospective study of 42 patients. J Orthop Surg Res. 2020;15:201.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kallala R, Harris WE, Ibrahim M, Dipane M, McPherson E. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty. Bone Jt Res. 2018;7:570–9.

    Article  CAS  Google Scholar 

  29. Emara K. Hemi-corticotomy in the management of chronic osteomyelitis of the tibia. Int Orthop. 2002;26:310–3.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ochsner PE, Gösele A, Buess P. The value of intramedullary reaming in the treatment of chronic osteomyelitis of long bones. Arch Orthopaedic Trauma Surg. 1990;109:341–7.

    Article  CAS  Google Scholar 

  31. Philandrianos G. Chronic nonhematogenous osteomyelitis treated with adjuvant CO2 laser sterilization: a preliminary report. J Clin Laser Med Surg. 1992;10:439–44.

    Article  CAS  PubMed  Google Scholar 

  32. Guelinckx PJ, Sinsel NK. Refinements in the one-stage procedure for management of chronic osteomyelitis. Microsurgery. 1995;16:606–11.

    Article  CAS  PubMed  Google Scholar 

  33. Pfeiffenberger J, Meiss L. Septic conditions of the shoulder ?an up-dating of treatment strategies. Arch Orthop Trauma Surg. 1996;115:325–31.

    Article  CAS  PubMed  Google Scholar 

  34. Yamashita Y, Uchida A, Yamakawa T, Shinto Y, Araki N, Kato K. Treatment of chronic osteomyelitis using calcium hydroxyapatite ceramic implants impregnated with antibiotic. Int Orthop. 1998;22:247–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Simpson AHRW, Deakin M, Latham JM. Chronic osteomyelitis. J Bone Jt Surg. 2001;83:403–7.

    Article  CAS  Google Scholar 

  36. Kuokkanen HOM, Tukiainen EJ, Asko-Seljavaara S. Radical excision and reconstruction of chronic tibial osteomyelitis with microvascular muscle flaps. Orthopedics. 2002;25:137–40.

    Article  PubMed  Google Scholar 

  37. Hashmi MA, Norman P, Saleh M. The management of chronic osteomyelitis using the Lautenbach method. J Bone Joint Surg Br. 2004;86:269–75.

    Article  CAS  PubMed  Google Scholar 

  38. Chang W, Colangeli M, Colangeli S, Di Bella C, Gozzi E, Donati D. Adult osteomyelitis: debridement versus debridement plus Osteoset T pellets. Acta Orthop Belg. 2007;73:238–43.

    PubMed  Google Scholar 

  39. Rao N, Hamilton CW. Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series. Diagn Microbiol Infect Dis. 2007;59:173–9.

    Article  CAS  PubMed  Google Scholar 

  40. Khan MAA, Jose RM, Taylor C, Ahmed W, Prinsloo D. Free radial forearm fasciocutaneous flap in the treatment of distal third tibial osteomyelitis. Ann Plast Surg. 2012;68:58–61.

    Article  CAS  PubMed  Google Scholar 

  41. Romanò CL, Logoluso N, Meani E, Romanò D, De Vecchi E, Vassena C, et al. A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis. Bone Jt J. 2014;96:845–50.

    Article  Google Scholar 

  42. Badie AA, Arafa MS. One-stage surgery for adult chronic osteomyelitis: concomitant use of antibiotic-loaded calcium sulphate and bone marrow aspirate. Int Orthop. 2019;43:1061–70.

    Article  PubMed  Google Scholar 

  43. Oosthuysen W, Venter R, Tanwar Y, Ferreira N. Bioactive glass as dead space management following debridement of type 3 chronic osteomyelitis. Int Orthop. 2020;44:421–8.

    Article  PubMed  Google Scholar 

  44. Al-Mousawi A, Sanese G, Baljer B, Lo Torto F, Hausien O, Perra A, et al. Use of the keystone perforator island flap in the treatment of chronic lower extremity wounds complicated by osteomyelitis. Injury. 2020;51:744–9.

    Article  PubMed  Google Scholar 

  45. Hotchen AJ, Dudareva M, Corrigan RA, Ferguson JY, McNally MA. Can we predict outcome after treatment of long bone osteomyelitis? Bone Joint J. 2020;102:1587–96.

    Article  PubMed  Google Scholar 

  46. Lorentzen AK, Engel L, Gottlieb H, Obinah MPB. One-stage treatment of chronic osteomyelitis with an antibiotic-loaded biocomposite and a local or free flap. Eur J Plast Surg. 2021;44:367–74.

    Article  Google Scholar 

  47. Bor N, Dujovny E, Rinat B, Rozen N, Rubin G. Treatment of chronic osteomyelitis with antibiotic-impregnated polymethyl methacrylate (PMMA) – the Cierny approach: is the second stage necessary? BMC Musculoskelet Disord. 2022;23:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Elhessy AH, Rivera JC, Shu HT, Andrews T-J, Herzenberg John E, Conway JD. Intramedullary canal injection of vancomycin- and tobramycin-loaded calcium sulfate: a novel technique for the treatment of chronic intramedullary osteomyelitis. Strateg Trauma Limb Reconstr. 2022;17:123–30.

    Article  Google Scholar 

  49. Luo Z, Dong Z, Ni J, Wei J, Peng P, Lv G. Distally based peroneal artery perforator-plus fasciocutaneous flap to reconstruct soft tissue defect combined with chronic osteomyelitis in the lateral malleolus. Int J Low Extrem Wounds. 2022;21:464–70.

    Article  PubMed  Google Scholar 

  50. Jiamton C, Apivatgaroon A, Aunaramwat S, Chawalitrujiwong B, Chuaychoosakoon C, Suwannaphisit S, et al. Efficacy and safety of antibiotic impregnated microporous nanohydroxyapatite beads for chronic osteomyelitis treatment: a multicenter, open-label. Prospect Cohort Study Antibiot. 2023;12:1049.

    Article  CAS  Google Scholar 

  51. Langit MB, Tay KS, Al-Omar HK, Barlow G, Bates J, Chuo CB, et al. Surgical debridement in long bone chronic osteomyelitis: Is wide tumour-like resection necessary? Bone Jt Open. 2023;4:643–51.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Sambri A, Cevolani L, Passarino V, Bortoli M, Parisi SC, Fiore M, et al. Mid-term results of single-stage surgery for patients with chronic osteomyelitis using antibiotic-loaded resorbable PerOssal® beads. Microorganisms. 2023;11:1623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Perry CR, Ritterbusch JK, Rice SH, Davenport K, Burdge RE. Antibiotics delivered by an implantable drug pump: a new application for treating osteomyelitis. Am J Med. 1986;80:222–7.

    Article  CAS  PubMed  Google Scholar 

  54. McNally M, Small J, Tofighi H, Mollan R. Two-stage management of chronic osteomyelitis of the long bones: the Belfast technique. J Bone Jt Surg Br. 1933;75:375–80.

    Article  Google Scholar 

  55. Alonge TO, Ogunlade SO, Omololu AB. The Belfast technique for the treatment of chronic osteomyelitis in a tropical teaching hospital. Int Orthop. 2003;27:125–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zweifel-Schlatter M, Haug M, Schaefer DJ, Wolfinger E, Ochsner P, Pierer G. Free Fasciocutaneous Flaps in the Treatment of Chronic Osteomyelitis of the Tibia: A Retrospective Study. J Reconstr Microsurg. 2006;22:041–8.

    Article  Google Scholar 

  57. Wu CH, Yuan LJ, Chan YS, Chen AC, Lee MS, Ueng SW. Conditions affecting treatment of pertrochanteric osteomyelitis. Chang Gung Med J. 2007;5:414–22.

    Google Scholar 

  58. Buono P, Castus P, Dubois-Ferrière V, Rüegg EM, Uçkay I, Assal M, et al. Muscular versus non-muscular free flaps for soft tissue coverage of chronic tibial osteomyelitis. World J Plast Surg. 2018;7:294–300.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wu H, Yu S, Fu J, Sun D, Wang S, Xie Z, et al. Investigating clinical characteristics and prognostic factors in patients with chronic osteomyelitis of humerus. Burns Trauma. 2019;7:1.

    Article  Google Scholar 

  60. Finelli CA, dos Reis FB, Fernandes HA, Dell’Aquila A, Carvalho R, Miki N, et al. Intramedullary reaming modality for management of postoperative long bone infection: a prospective randomized controlled trial in 44 patients. Patient Saf Surg. 2019;13:39.

    Article  PubMed  PubMed Central  Google Scholar 

Download references




The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations



All authors contributed to the study conception and design. Data collection and analysis were performed by AL, AE, MM, AW, BP. Supervision and administration were performed by AL and HS. The first draft of the manuscript was written by AL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ali Lari.

Ethics declarations

Ethical approval

Ethical approval was not required for the purpose of this review.

Competing interest

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lari, A., Esmaeil, A., Marples, M. et al. Single versus two-stage management of long-bone chronic osteomyelitis in adults: a systematic review and meta-analysis. J Orthop Surg Res 19, 351 (2024).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: