Osteomyelitis (OM) remains one of the most feared complications in bone surgery and trauma. Its diagnosis remains a major challenge due to lack of guidelines. The aim of this study was to prospectively analyze the value of the most common and available diagnostic tools and to establish an OM score to derive treatment recommendations. All patients with suspected OM were included in a prospective pilot study. All patients underwent blood sampling for C-reactive protein and white blood cell count analysis. Magnetic resonance imaging (MRI), and microbiologic and histopathologic samples, were taken from representative sites of initial debridement. All patients were treated according to their OM test results and followed for at least one year. Subsequently, the value of individual or combined diagnostic tools was analyzed in patients with confirmed OM and in patients in whom OM was ruled out. Based on these findings, an OM score was developed that included MRI, microbiology, and histopathology. The score identified all control patients and all but one OM patient, resulting in a correct diagnosis of 93.3%, which was validated in a second independent larger cohort. This was the first study to analyze the value of the most commonly used tools to diagnose OM. The proposed OM score provides a simple scoring system to safely interpret test results with high accuracy.

Background: Osteomyelitis, particularly affecting the lower extremities, is a serious and increasingly common complication. Accurate diagnosis is essential for successful treatment, yet standardized evidence-based protocols are lacking and diagnostic knowledge remains limited. This study aimed to identify characteristic histological and MRI findings in osteomyelitis to support diagnostic accuracy and guide treatment decisions. Methods: In a prospective case-control pilot study conducted from February 2020 to January 2021, all patients with suspected osteomyelitis of the lower limbs were included. Each underwent contrast-enhanced MRI and sampling for microbiological and histological analysis. Findings from five confirmed osteomyelitis cases were compared to five controls where osteomyelitis was ruled out. Results: All osteomyelitis cases showed typical MRI signs, including contrast-enhancing bone edema. Two had early, and two had pronounced intramedullary abscesses. In three controls, contrast-enhancing edema was limited to soft tissue; two showed mild adjacent bone edema. Histologically, all osteomyelitis samples revealed bone fragmentation and inflammatory cell infiltration—absent in controls. Additionally, four showed medullary fibrosis and one fibrin deposits. Conclusions: A comprehensive understanding of both histological and radiological findings is key to effective osteomyelitis treatment. This pilot study is the first to systematically compare MRI and histology findings side by side, offering valuable insights that may enhance diagnostic precision and support evidence-based treatment decisions.