https://orcid.org/0000-0001-9831-5681
Figures
Abstract
Objectives
Infection leading to necrosis of any bone can lead to chronic osteomyelitis (CO), sometimes resulting in permanent orthopedic sequelae. There are no published guidelines on the optimal management of adult or pediatric CO The objective of this study was to analyze published evidence for the epidemiology and management of pediatric CO.
Methods
Inclusion criteria were studies of any design (minimum 2 patients) in any language that included patients with CO up to 17 years of age and described the epidemiology or management of CO. Ovid Medline(R) ALL, Embase (via Ovid), CINAHL Plus with Full Text (via EBSCOhost) and Scopus were screened Jan 1, 1989 to Feb 13, 2025. Quality assessment was based on the degree of bias if one were to use that study to make decisions about management of CO. Studies were divided into those from middle-high and high-income countries versus studies from lower income countries. Data were extracted on demographics, biomarkers, pathogens, treatments offered, recurrences and orthopedic sequelae.
Results
There were 41 included studies – 26 from middle-high- and high-income countries (904 cases total) and 15 from lower income countries (975 cases total). All were observational and only 19 of the 41 studies reported 7 or 8 of the 8 items deemed essential to make decisions about management of CO. Definitions of CO varied markedly. Analyzing the 17 studies that included a minimum of 10 consecutive cases, 627 of 1073 cases (58%) occurred in males. In these 17 studies, the tibia or femur accounted for 630 of 934 cases (67%). In 212 of 287 cases (74%) with a single pathogen reported, that pathogen was Staphylococcus aureus. There were no apparent differences in sex, bones involved or pathogens by country income level. Most cases (with the notable exception of those in recent case series from the United States) were managed with debridement. This was typically followed by sequential intravenous/per os (IV/ PO) antibiotics with almost no patients managed with PO antibiotics alone. Twelve case series reported use of local antibiotic delivery in addition to systemic antibiotics, but none of these studies had a control group. Studies were too heterogeneous in design to allow for data to be directly compared or combined. However, there was no obvious relationship between the route or duration of antimicrobials and the incidence of recurrences or orthopedic sequalae.
Citation: Robinson JL, Gashgarey D, Alruqaie N, Dennett L, Pedersen ME (2025) The epidemiology and management of chronic osteomyelitis in pediatrics – A systematic review. PLoS One 20(12): e0337516. https://doi.org/10.1371/journal.pone.0337516
Editor: Nan Jiang, Southern Medical University Nanfang Hospital, CHINA
Received: August 27, 2025; Accepted: November 10, 2025; Published: December 2, 2025
Copyright: © 2025 Robinson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Raw data are now included in the manuscript as supplementary file S2.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Chronic osteomyelitis (CO) was recently characterized as ”a protracted, often indolent disease process with [1] presence of a sequestrum and/or [2] relapse of infection in the same site (bone) weeks to years after apparently successful treatment of the initial infection in that site.” [1] CO has been divided into five types: i) CO occurring post-acute hematogenous osteomyelitis (AHO), ii) primary hematogenous CO with no preceding AHO, iii) CO from a contiguous focus, iv) CO from orthopedic hardware and v) post-trauma CO [2]. A recent survey of pediatric infectious diseases physicians in the United States and Canada demonstrated “tremendous variability” in the management of CO [3].
Major barriers to studying CO are the lack of a uniform definition and the heterogeneity of clinical presentations and severity. Another barrier is that chronic non-bacterial osteomyelitis (CNO) is often initially confused with CO with clues being that CNO often involves the axial skeleton and sometimes eventually involves more than one bone.
Management options for CO include combinations of parenteral and oral antibiotics and surgical debridement with or without direct placement of antibiotics in bone. Removal of orthopedic hardware is considered optimal when CO is associated with previous orthopedic surgeries, especially if bony fusion has already occurred or if cure is not achieved with other options.
The objective of this review was to systematically review the literature on management and outcomes of pediatric CO and summarize the demographics, pathogens, treatments offered, and outcomes.
Materials and methods
This was a systematic review of the interventions and outcomes of pediatric patients with CO. The primary outcome was the recurrence rate. We analyzed cases separately in upper-middle- or high-income countries versus low or lower-middle income countries as patients in resource-poor countries often present with very advanced disease so would be predicted to have poorer outcomes.
This review was not registered.
Inclusion criteria
Inclusion criteria were studies of any design in any language of CO (however the authors defined it) with or without orthopedic hardware that included minimum 2 patients up to 17 years of age.
Exclusion criteria
Exclusion criteria were studies that:
- 1) included adults unless pediatric cases were reported separately or a minimum of 80% of cases were pediatric.
- 2) combined sub-acute osteomyelitis (using whatever definition the authors chose) and CO.
- 3) reported primarily radiographic findings or surgical techniques.
- 4) included primarily cases now considered to be non-infectious (chronic recurrent multifocal osteomyelitis or CNO or mandibular case series).
- 5) were published prior to 1989, an arbitrarily chosen year as studies prior to that appeared to mainly be poor quality.
Search methodology
A health sciences librarian searched Ovid Medline(R) ALL, Embase (via Ovid), CINAHL Plus with Full Text (via EBSCOhost) and Scopus from Jan 1,1980 until Feb 13, 2025. The search combined the concepts of chronic osteomyelitis and children (S1 File). Single case reports and conference abstracts were excluded. The search was validated by checking that it included numerous seed articles the authors had previously identified. Results from all searches were downloaded to Covidence (Veritas Health Information, Melbourne Australia) where they were deduplicated. Reference lists of included articles and reviews were reviewed for additional studies. Two independent reviewers screened the title/abstracts according to the inclusion and exclusion criteria. Conflicts were resolved through discussion.
Data extraction
Data were extracted by one reviewer, including demographics, the biomarkers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell count (WBC), pathogens, treatment and outcomes (recurrences or orthopedic sequalae) and entered into REDCap. Organisms isolated from bone or operative specimens were considered pathogens. Based on studies showing markedly discrepant results from sinus and bone cultures [4,5], organisms isolated from pus, sinuses or fistulas were not included.
Data analysis
Case series were classified into those where patients lived in upper-middle- or high-income countries versus low or lower-middle income countries as determined by the World Bank [6].
To determine the distribution of sexes, bones involved and pathogens, data were combined from series with minimum 10 cases where it seemed likely that consecutive cases of CO of all bones were enrolled.
The initial plan was to perform a meta-analysis of outcomes but this was not conducted due to i) the heterogeneity of CO definitions ii) the fact that often minimal or no data were provided on the initial management of cases that recurred and iii) the markedly variable durations and completeness of follow-up.
Data are reported as per the PRISMA guidelines (S2 File).
Quality Assessment
Two reviewers independently assessed each study and then reached consensus through discussion on answers to the following questions, modified from the NIH Study Quality Assessment Tools | NHLBI, NIH and JBI JBI Critical Appraisal Tools | JBI tools to fit the current review by assessing the degree of bias if one were to use that study to make decisions about management of CO:
- Was there a case definition?
- Were cases stated to be or presumed to be consecutive?
- Was there clear reporting of sex, age, bones involved and pathogens?
- Was the mean duration of antibiotic therapy reported?
- Is it reported how many cases had surgery at initial diagnosis of CO?
- Is it reported how many cases required further antibiotics or surgery after the initial intervention?
- Was minimum 6 months follow-up for recurrence reported for over half of patients?
- Was minimum 6 months follow-up for orthopedic sequelae reported for over half of patients?
Studies were excluded only if they had no affirmative answers.
Results
Search
The search yielded 1139 unique titles and abstracts of which 41 met the inclusion criteria (Fig 1). A case series labelled CO of the clavicle was excluded as most likely had CNO [7]. The Canavese study [8] was excluded as all patients appeared to be included in the Rousset study [9]. Studies by Yeargan [10] and Matzkin [11] were both included, recognizing that there may be overlap for tibial CO managed in Honolulu 1990–1998. Data reported by Stevenson [12] and Beckles [13] were combined as they reported the same patients. Data as entered into REDCap are provided in S3 File.
Quality assessment
All the studies included were observational. Quality assessment is shown in Table 1 with the number of reported items out of 8 being 0 (n = 0), 1–3 (n = 7), 4–6 (n = 15) and 7 or 8 (n = 19).
Demographics and diagnostic features
There were 26 case series from upper-middle or high income and 15 from low or low-middle income countries (Table 2) reporting a total of 904 and 975 cases, respectively. The definitions of CO varied markedly, requiring a minimum of 10 days to 6 months of a variety of signs and symptoms (Table 2). Three case series reported the percentage of all osteomyelitis cases that presented as CO: 86% in Ethiopia [17], 66% in Nigeria [26] and 54% in Fiji [25].
In studies where biomarkers were reported, ESR was elevated in 55–100% and CRP in 11–100% of cases; WBC count was usually normal (Table 2). The percentage of cases with positive blood cultures were reported in two studies: 7/343 (2%) (18), and 5/67 (7%) [2]; it is not reported how many patients in these studies had blood cultures performed.
There were 20 studies that reported minimum 10 presumed consecutive CO cases. Cases were male in 627 of 1073 (58%) cases – 244/ 452 (54%) in 6 studies from middle-high and high income countries [18,33,37,38,43,44] and 383/621 (62%) in 11 studies from low and middle low income countries [11,12,15,22,23,26,30,32,41,45,47] (data missing for three studies [2,25,46]). The bones involved are shown in Fig 2 (data missing for 3 studies [18,26,46]), with 630 of 934 (67%) involving the tibia or femur; there are no apparent differences in the bones involved related to income level of country of origin. The pathogens were reported in 10 of these 20 studies as shown in Table 3. Staphylococcus aureus was isolated from 212 of 286 cases (74%) that reported a single pathogen – 77/115 (67%) in higher income countries and 135/171 (79%) in lower income countries. All other pathogens were isolated from 11 or fewer cases, even with all case series combined. McNeil is the only study that analyzed pathogens by type of CO. Post AHO CO was almost always due to S. aureus, but for all other types of CO, S. aureus accounted for a minority of cases [2].
Percentages on the right are from 604 cases in 10 studies from low and low-middle income countries. Fig created by Biorender.
Treatment and outcomes
All cases received antibiotics except for three cases managed with multiple surgeries [10] and one case ultimately labelled chronic multifocal osteomyelitis (Table 4). Patients managed with per os (PO) antibiotics alone were limited to two with Q fever [28] and possibly some of the 167 reported by Beckles [13] (cases with sclerosis were treated with 6 weeks PO flucloxacillin but it is not clear how other cases were managed). All cases in all other case series received intravenous (IV) antibiotics, usually followed by PO antibiotics for widely variable durations. Few studies provided complete data on choice of antibiotics.
In addition to systemic antibiotics, vancomycin [19,21], tobramycin [24] or gentamicin [9,34,37,44] alone or in combination [15,22,40] or unspecified antibiotics [13] were directly implanted into bone via cement, polymethylmethacrylate (PMMA) or calcium sulphate at initial debridement in 12 studies from 1997 to 2023 for 4–40 patients (mean 14) (Table 4). A study with vancomycin also used bioactive glass [21] (which has antibacterial properties) while another used bioactive glass alone [20,21]. No studies had a control group that received only systemic antibiotics. All report initial success, but one that used gentamicin reported that 6 of 40 had recurrences at 23 days to 3.5 years with one having a second recurrence 9 months later [37].
In most studies, all patients had at least one surgery with the notable exception of two recent United States (US) series where 34 of 114 (30%) [2] and 280 of 343 (82%) [18] were managed with antibiotics alone.
Table 4 shows the incidence of recurrences and orthopedic sequelae. The highest rates of recurrence were 26% in studies from the US [2] and from Fiji [25]. Typically, minimal data were provided on the characteristics or prior therapy of those with recurrences so this could not be further analyzed. A statistical comparison of outcomes was not conducted given the heterogeneity of definitions and incomplete descriptions of management, but there is no obvious link between the duration or route of delivery of antibiotics and outcomes.
Discussion
This review summarizes 41 studies of pediatric CO. All were case series. There was no other study types identified. Sixteen did not provide a definition of CO. Each of the other 25 studies applied a unique definition. A Brodie abscess, sequestrum, or involucrum are proof of CO and are sometimes apparent on imaging. Other times the diagnosis is based on the presence of a sinus tract or on recurrence following completion of treatment for AHO. From the 41 studies, the McNeil definition would appear to be the most comprehensive: “ [1] symptoms suggestive of osteomyelitis (e.g., pain, swelling, warmth, erythema, drainage, loss of function, etc.) lasted ≥28 days on presentation or [2] there was a clearly documented history of acute osteomyelitis in a patient who received at least 4 weeks of effective antimicrobial therapy along with (a) new or worsening drainage, swelling, erythema, pain or loss of function; (b) radiographic evidence of sequestrum or permeative lucencies; or (c) readmission for the management of osteomyelitis” [2]. This definition should be considered for future studies.
It seems likely that the prognosis and optimal treatment vary by type of CO and by the volume of necrotic bone at presentation. Risk factors for post-AHO CO are not clear, but one study reported a higher risk if early bone ischemia was reported on MRI performed for AHO [14]. In the presence of orthopedic hardware, it is not clear how to differentiate acute from chronic osteomyelitis.
Optimal surgical management of CO is not clear from this review. The majority of cases had debridement, but some were cured without surgery. It seems likely that the need for debridement depends upon the volume of necrotic bone; recurrence may correlate with the volume of residual necrotic bone following surgery. For the US study where only 18% of cases had surgery [18], the diagnosis of CO was based on discharge diagnostic codes alone; it seems likely that some would not be classified as CO in other studies. Given the paucity of high-quality evidence that CO can be cured with antibiotics alone, debridement would seem to be indicated in most cases to remove necrotic bone and collect cultures.
In terms of antimicrobials, it is not clear from this review whether all patients require systemic antibiotics if adequate debridement is achieved. However, only 3 CO cases were managed without antibiotics [10] so clearly most clinicians consider them mandatory. The role of PO versus IV antibiotics is not clear. Very few patients received only PO antibiotics. However, a recent study reported that AHO can usually be managed with PO antibiotics alone [50], so perhaps IV antibiotics are only required if the patient is septic (which is rare with CO) or if absorption of or compliance with PO antibiotics is doubtful.
It was not possible to analyze the efficacy of specific antibiotics for CO as the choice of antibiotics was often not reported in detail, including in cases with recurrences. Whenever practical, cultures from bone should be obtained prior to administration to guide antibiotic choice. Assuming another pathogen was not previously detected from an operative specimen, empiric antibiotics should target S. aureus (with methicillin resistant S. aureus coverage if the local incidence is high) as this was the pathogen in about three-quarters of cases, recognizing that other pathogens may play an important role in types of CO other than post-AHO CO [2]. When cultures are negative, molecular detection methods should be considered [51]. The role of combination antibiotics is not clear. Rifampin has excellent bone penetration so is sometimes added to other antibiotics to treat S. aureus [52]. A randomized controlled trial reporting a trend towards improved outcomes with the addition of rifampin to 42 days IV nafcillin in 18 adults with CO without orthopedic hardware [53]. There are discordant results regarding the efficacy of rifampin for other device-related infections in adults [54]. Rifampin is yet to be studied in pediatric CO.
Local delivery of antibiotics was reported in 12 studies, through antibiotic loaded PMMA cement beads or spacers that eventually need to be removed or through antibiotic loaded calcium sulphate which is biodegradable. It is not clear whether PMMA or calcium sulfate interferes with healing or whether nephrotoxicity ever occurs. Efficacy is impossible to establish from the 12 studies as there was never a control group. An observational study that was excluded from the current review as 29% of cases were adults reported improved outcomes with implanted gentamicin beads in tibial CO than in unmatched controls with gentamicin rinses delivered via closed lavage [55]. Regarding the choice of antibiotics for local delivery, vancomycin is likely to cover S. aureus. Although gentamicin and tobramycin are synergistic with beta lactams for treatment of methicillin-susceptible S. aureus (MSSA), one would never use them as monotherapy for MSSA. A Nigerian study reported use of non-commercial ceftriaxone beads (which would cover MSSA) in adults and children [56].
The total duration of antibiotics varied markedly in this review. A 2010 systematic review that differed from the current review in that they included sub-acute osteomyelitis reported markedly varying durations of IV and PO antibiotics with no relationship between duration and treatment failure [57]. This fits with the results of the current study.
A potential new intervention is an injectable in situ-forming depot antibiotics delivery system which appears hopeful in animal models [58]. Success with hyperbaric oxygen has been reported in adults [59] and in one child [60].
A key limitation of this review is the inconsistent definitions applied for CO which made it impossible to combine study results. One study required only 7 days of symptoms [46] which most experts would not consider to be CO. However, our protocol specified inclusion of studies that the authors considered to be CO; it would introduce bias to arbitrarily exclude studies. It is possible that some included patients had AHO or CNO. Organism reported to be pathogens could have been contaminants. Incomplete reporting of types of CO and antibiotic regimens limited our ability to correlate outcomes with management decisions. Only published studies were screened.
Conclusion
The results of this review should be applied to guide further study of CO. The first step is to settle on a definition. As previously stated, we favor the McNeil definition [2]. Debridement would seem to be indicated unless i) CO involves a small bone, ii) there is concern that debridement will contribute to bony instability, or iii) the lesion is too small to readily find. There is a need to compare outcomes with and without initial IV versus PO antibiotics. Beta lactams are typically used for AHO, but clindamycin, ciprofloxacin and trimethoprim-sulfamethoxazole have better bone penetration so should be compared to beta lactams for CO [52], with or without the addition of rifampin. The optimal duration of antibiotics probably depends upon the volume of residual necrotic bone post-debridement. Spellberg advocates a maximum 6-week course in adults [52], but a longer course can perhaps be justified if adequate debridement was not achieved. Given the rarity and heterogeneity of CO, multicenter randomized controlled trials may not be practical, so the next step could involve applying and studying a protocol in multiple centers. Hopefully advances in the next decade will improve the prognosis of pediatric CO worldwide.
Supporting information
S1 File. Search strategy.
This is the strategy for searching the literature.
https://doi.org/10.1371/journal.pone.0337516.s001
(PDF)
S2 File. PRISMA checklist.
This is the completed PRISMA checklist.
https://doi.org/10.1371/journal.pone.0337516.s002
(DOCX)
S3 File. Raw data.
This is the data as it was entered into REDCap.
https://doi.org/10.1371/journal.pone.0337516.s003
(DOCX)
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