Osteomyelitis in the diabetic foot

NewsBot · Jul 30, 2025

Novel Treatments for Diabetic Foot Osteomyelitis: A Narrative Review
Crystal Jing et al
Microorganisms. 2025 Jul 11;13(7):1639.

Diabetic foot osteomyelitis (DFO) is a severe complication of diabetes mellitus and a leading cause of non-traumatic lower extremity amputation. Treatment remains clinically challenging with high recurrence rates despite standard antibiotic therapy and surgical debridement. This narrative review synthesizes current evidence on novel operative and nonoperative therapies for DFO, focusing on emerging biomaterials, local antibiotic delivery systems, innovative surgical techniques, and adjunctive topical agents. Studies examining bioabsorbable and nonabsorbable antibiotic carriers, such as calcium sulfate beads, collagen sponges, and bioactive glass, demonstrate promising infection resolution rates and a potential to reduce the surgical burden, though most are limited by small cohorts and observational designs. Similarly, alternative surgical approaches (i.e., cancelloplasty, conservative bone excision, and tibial cortex distraction) have shown early success in limb preservation. Nonoperative strategies, including adjunct antimicrobials, antimicrobial peptides, and topical oxygen, offer additional options, particularly for patients unfit for surgery. While initial outcomes are encouraging, the supporting evidence is heterogeneous and primarily limited to case series and small, noncomparative trials. Overall, these novel therapies show potential as adjuncts to established DFO management, but further prospective research is indicated to define their long-term efficacy, safety, and role in clinical practice.
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NewsBot · Sep 20, 2025

The role of Cerament® (Antibiotic impregnated bone void filler) in lower limb salvage for diabetic foot patients with osteomyelitis, a scoping review
Ramy Elkady et al
The Surgeon 16 September 2025

Highlights

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Cerament G/V used as local antibiotic carriers in diabetic foot osteomyelitis.
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Evidence suggests improved infection control and lower limb salvage rates.
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Studies report overall good safety profile.
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Current evidence limited to small, heterogeneous observational studies
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High-quality trials and long-term outcomes are needed to support broader use.

Abstract
Background
Diabetic foot osteomyelitis (DFO) is a principal cause of non-traumatic lower limb amputation, contributing substantially to morbidity, healthcare costs, and reduced quality of life. Salvage optimization strategies have included the use of local antibiotic carriers to promote healing and reduce infection recurrence. Cerament, either G (gentamicin) or V (vancomycin), resorbable antibiotic-loaded bone graft substitute, has shown potential, but evidence has not been systematically mapped.
Objective
This scoping review aimed to map and summarize the available literature on the role of Cerament G and V in lower limb salvage among patients with DFO.
Methods
A systematic search of PubMed, Embase, the Cochrane library, and Google scholar [December 2024]. Studies reporting outcomes of Cerament G or V in the management of DFO were eligible. Data were charted according to PRISMA-ScR guidelines, focusing on study design, intervention details, and key findings.
Results
A total of 20 studies were identified, including [case reports, case series, retrospective reviews, and prospective cohorts]. Population within the studies ranged from 1 to 136. Reported outcomes included wound healing, eradication of infection, weight bearing, new bone formation and high antibiotic concentration without systemic toxicity. Amputation rates ranged from 2.6 % to 25 %. Evidence is limited by small sample sizes, heterogeneity in outcome reporting, and lack of randomized controlled trials.
Conclusion
Current evidence suggests that Cerament G and V may be safe and effective adjuncts for limb salvage in DFO, but high-quality comparative studies are lacking. Further research is needed to support its broader use in daily practice.
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NewsBot · Sep 27, 2025

Radical surgical treatment of calcaneal osteomyelitis: clinical characteristics and treatment efficacy based on a synthesis analysis of 364 reported cases
Zi-Xian Liu et al
J Orthop Surg Res. 2025 Sep 26;20(1):838.

Background: Calcaneal osteomyelitis (CO) poses substantial therapeutic challenges due to the distinctive anatomy and function of the calcaneus. Although multiple treatment modalities are available, severe cases frequently require radical surgical interventions, such as partial or total calcanectomy, and even amputation. Nevertheless, the clinical profile of these patients is not well characterized. Consequently, this study aimed to examine and elucidate clinical characteristics and treatment outcomes of CO patients who have undergone radical surgical interventions.

Methods: A systematic literature search was conducted by two independent authors across the PubMed, Embase, and Cochrane Library databases to identify English-language studies published between January 1, 2000, and December 31, 2021, focusing on patients with CO who had undergone partial or total calcanectomy, as well as limb amputation. Studies were selected based on pre-defined inclusion and exclusion criteria. Quality assessment was performed using the National Institutes of Health (NIH) assessment tool, and effective data were extracted and synthesized for analysis.

Results: Altogether 364 CO patients were enrolled, with a male-to-female ratio of 1.88:1 (188 males and 100 females). The median age at diagnosis was 58.5 years. Diabetic foot ulcers emerged as the predominant cause, and pathogen cultures indicated a high positivity rate of 97.2% (106/109). Staphylococcus aureus was the most commonly isolated strain at 33.3% (20/60), with polymicrobial infection accounting for 24.1% (19/79). The overall infection recurrence rate was 33.1% (105/317), with total calcanectomy and partial calcanectomy being 45% (18/40) and 30.4% (72/237), respectively. Among the 104 patients who underwent amputation procedures, 49 patients were subjected to primary amputations, with the remaining 55 patients receiving secondary amputations following partial or total calcanectomy. The majority of secondary amputations, specifically 78.2% (43/55), occurred after partial calcanectomy, whereas 21.8% (12/55) followed total calcanectomy. The overall mortality rate across all the 345 patients was 5.8%, with no fatalities being directly attributable to CO.

Conclusions: In this cohort of patients that received radical surgical interventions, the majority were middle-aged males, and the diabetic foot ulcer was the leading cause. Staphylococcus aureus continued to be the most frequently isolated pathogen. Even among patients who received partial and total calcanectomy, clinical efficacy remained unsatisfactory due to high rates of infection recurrence, leading to a high incidence of secondary limb amputation.
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NewsBot · Sep 28, 2025

Neuroinflammation and osteomyelitis in adults with Type 2 diabetes mellitus and peripheral neuropathy without and with foot lesions. What comes first?
Maria Sambataro et al
Journal of Diabetes and its Complications 24 September 2025, 109176

Highlights
The “disease of the foot” as for IWGDF 2023 definition”includes the presence, but not explains the hierarchy of: peripheral neuropathy, peripheral artery disease, infection, ulcer(s), neuro‐osteoarthropathy, gangrene, or amputation. But what comes first?
We explored:

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The distribution of mNGF and proNGF in blood samples and foot bones, their correlation with functional neuropathy, depth of lesions and tissue oxygenation.
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The expression of CX3CR1 on circulating monocytes and its correlation with neuroischemia, delta postural hypotension, tissue oximetry and proNGF.
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The early bone response to hyperglycemia correlating with fractalkine/CX3CL1, RORγ and apoptotic signals and the resultant altered bone structure (i.e. non-infected inflammatory osteomyelitis).

If sensory and autonomic neuropathy expressing proNGF have a role in self-bone destruction, leveraging the interruption of this neuro-skeletal axis could be the target of future therapies aimed to avoid amputations.
Abstract
Aims
Diabetic foot is the leading cause of both major and minor non-traumatic amputations yet a truly understanding of the phenomenon is still lacking. The updated definition for diabetes-related foot disease from the International Working Group on the Diabetic Foot (IWGDF 2023 update) is “disease of the foot of a person with current or previously diagnosed diabetes mellitus that includes one or more of the following: peripheral neuropathy, peripheral artery disease, infection, ulcer(s), neuro‐osteoarthropathy, gangrene, or amputation”, but what comes first? Our hypothesis is that distal sensory and autonomic neuropathy activate neuroischemic signaling and dysregulation of bone cell apoptosis portending to infections.
Methods
We studied 374 adults with Type 2 diabetes mellitus (T2DM) and diabetic neuropathy (DN) divided into the following subgroups: 106 partecipants without foot lesions (DNp); 119 nonmacrovascular partecipants with ulcers/lesions/osteomyelitis (DNpU); 149 revascularized partecipants with ulcers/lesions/osteomyelitis (DNpUV) and a group of 53 healthy adults as healthy control (NC). During routine foot care visits participants underwent neuro electrophysiology tests and vascular assessment. Biopsy specimens from exposed bone (grade III University of Texas wound classification, TUC) were cultured according to microbiological standards and histological analysis was performed. Pro/anti-inflammatory cytokines and blood cells subsets (lymphocytes subpopulations, classical, non-classical and SLAN+ monocytes, classical DCs, innate lymphoid cells) were analyzed. Nerve Growth Factor (NGF) species, fractalkine/CX3CL1 migration marker, autophagy markers (Ulk1, Beclin1, LC3, and p62), pro/anti-apoptotic proteins (Bax, Bcl2, cleaved Caspase-3), signal transduction of proteins involved in inflammation and cell survival (p65-NF-kB, Akt and ERK1/2) were measured.
Results
Sural nerve (sS) conduction velocity (CV) and sensory Action Potential (sAP) thresholds defined DN. II and III TUC associates with progressive worsening of neuronal function while vibration perception threshold (VPT) and systolic/diastolic orthostatic hypotension inversely correlated with TcPO2 and critical ischemia. In III TUC versus I TUC diabetic foot ulcer (DFU) and DNp samples the amount of circulating mature NGF (mNGF) was significantly reduced (p < 0.01) while immature NGF (proNGF) was significantly increased (p < 0.05). In all groups we found higher number of SLAN+ monocytes co-expressing CX3CR1 directly correlating with proNGF levels, worse autonomic and sensory testing and inversely correlating with mNGF levels, sensory nerves CV and AP, innate lymphoid cells and subsets of lymphocytes. Surprisingly, we found 59 bone's biopsies with an altered histological pattern but negative microbiological cultures. In all biopsied patients CX3CR1-SLAN+ cells were significantly elevated (p < 0.05) independently of concomitant infective osteomyelitis in III TUC versus the level measured in I TUC and DNp. Cleaved caspase 3 and Bax directly correlated with % of CX3CR1+SLAN+CD16+ inflammatory monocytes and inversely with bone ERK1/2 activating phosphorylation.
Conclusions
DN could be an important factor in diabetic foot. Reduced proprioception and sympathetic orthostatic hypotension destroy structures of the foot, alter intrabone neurotrophins resulting in vascular signaling, early activation of bone apoptosis and CX3CR1+monocytes prior to and independently of infected osteomyelitis. These data suggest a new interpretation of the main players involved in the physiopathology of diabetic foot and may mark the way for the development of new targeted therapies.
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NewsBot · Oct 1, 2025

Role of Biomarkers in Diabetic Foot Osteomyelitis
Monika Gureh et al
J Orthop Case Rep. 2025 Sep;15(9):342-347.

Introduction: Foot ulcer is one of the common problems in patients with diabetes mellitus. The spectrum of diabetic foot infection is wide, ranging from cellulitis and soft tissue infection to osteomyelitis (OM). OM requires further testing and investigations and even longer treatments. The aim of this prospective study was to assess the performance of serum markers, namely, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) in the diagnosis and follow-up of patients with diabetic foot osteomyelitis (DFO) and to find correlation between serum levels of these biomarkers and treatment response.

Materials and methods: This prospective study was carried out in 50 patients. Diagnosis of OM was made by clinical examination and confirmed by radiological studies. The serum levels of ESR, CRP, and PCT were determined on admission in all the patients and then on day 15 and day 30 in the osteomyelitic group.

Results: No significant difference was observed in the levels of ESR, CRP, and PCT in DFO and non-OM patients (P > 0.05) at presentation. However, there was a significant difference (P > 0.05) in levels of these markers between patients with healed and non-healed lesions in the osteomyelitic group on day 15 and day 30.

Conclusion: Biomarkers may not help in diagnosing OM. However, the level of biomarkers decreases significantly in response to treatment validating their role in predicting healing.
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NewsBot · Oct 13, 2025

Diagnostic value and integrated threshold of ESR for diabetic foot osteomyelitis: a systemic review and meta-analysis
Lulu Liu et al
Front Endocrinol (Lausanne). 2025 Sep 25:16:1660465.

Background: Diabetic foot osteomyelitis (DFO) is a severe complication of diabetic foot infections (DFI). Early and accurate diagnosis is crucial for improving patient outcomes. The erythrocyte sedimentation rate (ESR), a commonly used inflammatory marker, has been controversial regarding its diagnostic value and optimal cutoff values in DFO.

Objective: This study aims to conduct a systematic review and meta-analysis to comprehensively evaluate the diagnostic efficacy of ESR for DFO and to determine an optimal pooled cutoff value for the marker.

Methods: A systematic search of PubMed, EMBASE, Cochrane Library, OVID, and the Wanfang database was conducted for literature related to ESR in the diagnosis of DFO, with the search period extending through March 2025. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied for quality evaluation of the included studies. Statistical analyses were performed using Stata 18.0 to generate hierarchical summary receiver operating characteristic (HSROC) curves and forest plots for assessing the diagnostic performance of ESR in DFO. To determine the optimal composite cutoff value of ESR for diagnosing DFO, a different random intercepts and common random slope (DICS) model was implemented using R4.5.0. Subsequently, a Generalized Linear Mixed Model (GLMM) was constructed to predict the corresponding sensitivity and specificity at the ESR threshold of 70 mm/h.

Results: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 12 studies with a total of 1,674 subjects were included. The HSROC model revealed that the area under the curve (AUC) for ESR in diagnosing DFO was 0.71, with sensitivity and specificity values of 0.76 and 0.73, respectively. The DICS model identified an optimal pooled cutoff value for ESR at 51.6 mm/h, with corresponding sensitivity and specificity values of 0.80 and 0.67, respectively. Using the GLM model, an ESR cutoff of 70 mm/h yielded sensitivity and specificity of 0.61 and 0.83, respectively.

Conclusion: ESR demonstrates moderate diagnostic efficacy in the identification of DFO. Based on our findings, we recommend the optimal pooled cutoff value for ESR is 51.6 mm/h, as a preliminary screening tool in the diagnostic workup of DFO.
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NewsBot · Oct 27, 2025

Heel Diabetic Foot Osteomyelitis: A Current Challenge in the Clinical Practice
Martina Salvi et al
Int J Low Extrem Wounds. 2025 Sep 29

The current study aimed to evaluate the outcomes of heel diabetic foot osteomyelitis (DFO) managed in a specialized diabetic foot service. The research is a single-center retrospective observational study including a population of patients with diabetic foot ulcers (DFUs) complicated by DFO and requiring hospitalization, managed between 2019 and 2022 in a tertiary level diabetic foot service. According to the location of bone infection, patients were divided into two groups: those with heel DFO and those with forefoot/midfoot DFO. After one year of follow-up, the following outcomes were evaluated and compared between groups: healing, healing time, major amputation, and mortality.Overall, 114 patients were included. The mean age was 67.9 ± 12, most of them were male (72.8%) and had type 2 diabetes (91.2%); 84 (73.7%) of patients reported forefoot/midfoot DFO, while 30 (26.3%) reported heel DFO. Patients with heel DFO showed greater rates of soft tissue infection (80 vs 68.7%, p = 0.04), ulcer size >5 cm (93.3 vs 34.3%, p = <0.0001), gangrene (63.3 vs 22.9%, p = <0.0001), higher C-reactive protein values (67.6 ± 25 vs 24 ± 16 mg/dl, p = 0.0002) and concomitant peripheral arterial disease (PAD) (83.3 vs 52.4%, p = 0.0002).Outcomes for heel DFO and forefoot/midfoot DFO were: wound healing (66.7 vs 97%, p = <0.0001), healing time (14 ± 6 vs 6.8 ± 5 weeks, p=<0.0001), major amputation (10 vs 0%, p = 0.0002), and mortality (6.6 vs 4.8%, p = 0.3) respectively. At the multivariate logistic regression analysis, heel DFO [OR 8.4, CI95% (2.1-14.8), p=<0.0001] and PAD [OR 3.5, CI95% (1.1-4.2), p = 0.001] were independent predictors of major amputation, while heel DFO [OR 6.8, CI95% (1.9-10.5), p=<0.0001], PAD [OR 4.8, CI95% (1.4-7.6), p = 0.0001], and ulcer size [OR 1.5, CI95% (1.2-2.6), p=<0.0001] were independent predictors of non-healing.Heel DFO resulted associated with a higher risk of major amputation and reduced chance of healing.
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NewsBot · Oct 29, 2025

Evaluating Negative Margins in Foot Amputations for Diabetic Osteomyelitis: How Do We Decide?
Amanda Anderson et al
Foot Ankle Spec. 2025 Oct 2:19386400251364978.

Background: Amputation level in diabetic foot osteomyelitis (DFO) is most determined based on surgeon visualization of macroscopic criteria, leading to subjective variability. Wide variance in methods of bone histological analysis and culture are utilized to determine the presence of residual infection. We therefore conducted a systematic, qualitative review to evaluate the current available data on objective measures to delineate the appropriate level of resection in diabetic toe and forefoot amputations, as well as the accuracy of different methods to assess for persistent infection.

Methods: We performed a systematic review of studies from 1990 to 2023 performed on methods to determine margins in toe and forefoot amputations for DFO following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data were summarized to discuss the study main objectives, methods utilized to determine amputation level, and techniques used to assess margins for persistent deep infection.

Results: 568 articles were identified, and 18 articles met the final inclusion criteria after review. All studies used plain radiographs for preoperative assessment. 13 used magnetic resonance imaging (MRI) as part of their algorithm to determine general amputation level and 3 used MRI to determine exact depth of resection. 15 studies used microbiological cultures and 13 used histopathological margins intraoperatively to assess margins for deep infection. Of those, 7 studies found that those with positive margins had higher rates of treatment failure.

Conclusion: Overall, majority of studies used combination of plain radiographs of MRI to determine amputation level. Patients who ultimately had positive margins correlated with longer antibiotic duration and higher rates of continued infection, impaired wound healing, reoperation, or readmission. Elucidating the optimal method of evaluating clean surgical margins is critical to lessen the burden on health care systems and improve patient care.
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NewsBot · Nov 12, 2025 at 7:19 PM

Osteomyelitis and Its Main Determinants in Patients With Diabetic Foot Ulcer: A Cross-Sectional Study
Soheil Bolandi et al
Health Sci Rep. 2025 Nov 9;8(11):e71463.

Background and aims: Diabetic foot ulcers (DFUs) represent a significant and prevalent complication of diabetes, imposing substantial psychological, financial, and healthcare burdens globally. Osteomyelitis, the most common complication of DFUs, is a primary cause of lower limb amputations in diabetic patients. This cross-sectional study aimed to evaluate the epidemiological and clinical aspects of patients with diabetic foot osteomyelitis (DFOM) resulting from DFU infection.

Methods: Hospital records with a diagnosis of diabetic foot wound infection were reviewed during a period of 8 months (April-December 2021). Osteomyelitis was diagnosed using magnetic resonance imaging criteria. Patients were categorized into two groups of with and without osteomyelitis, and compared accordingly for predisposing risk factors and also clinical outcome.

Results: Among 252 cases of DFU infection, 23.8% were confirmed to have DFOM. Multivariate logistic regression analysis identified lower age (p = 0.02; OR = 0.86; 95%CI: 0.75-0.98), lower BMI (p = 0.01; OR = 0.57; 95%CI: 0.382-0.86), higher income level (p < 0.001; OR = 8.62; 95%CI: 2.42-30.74), higher HbA1c level (p < 0.001; OR = 19.072; 95%CI: 7.61-47.78), and the location of the wound on the heel and leg as predictive factors for the occurrence of DFOM. Regarding the clinical outcomes, osteomyelitis was significantly associated with longer length of hospitalization (19.02 ± 2.58 vs. 14.53 ± 2.74 days), delayed wound healing (above 6 months: 40.0 vs. 8.8%), lower limb salvage (68.3 vs. 99.0%), higher rate of wound dehiscence (33.3 vs. 10.4%), and higher rate of wound recurrence (30.0 vs. 0.5%). The mortality rate was also higher in the osteomyelitis group (13.3 vs. 0%).

Conclusion: Approximately 23.8% of patients with DFU may develop osteomyelitis, which can be predicted by lower age, lower BMI, higher income level, higher HbA1c level, and the location of the wound. Early identification and appropriate management of these risk factors may help prevent osteomyelitis development in DFU patients.
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Osteomyelitis in the diabetic foot

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Non-surgical management of osteomyelitis in the diabetic foot

Probe-to-Bone Test for Diagnosing Diabetic Foot Osteomyelitis

Osteomyelitis help

Sever's disease complicated with osteomyelitis

Charcot Foot and Osteomyelitis

Osteomyelitis in Diabetes: A Marrowing Experience No Longer? - Dr F. Javier Aragón Sánchez MD - DF

osteomyelitis and removal of fibula

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Osteomyelitis in the diabetic foot

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Non-surgical management of osteomyelitis in the diabetic foot

Probe-to-Bone Test for Diagnosing Diabetic Foot Osteomyelitis

Osteomyelitis help

Sever's disease complicated with osteomyelitis

Charcot Foot and Osteomyelitis

Osteomyelitis in Diabetes: A Marrowing Experience No Longer? - Dr F. Javier Aragón Sánchez MD - DF

osteomyelitis and removal of fibula

Share This Page

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