Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management

ABSTRACT Osteomyelitis (OM) is a severe inflammatory bone disease caused by pathogen invasion, representing a major challenge in orthopedic surgery. Staphylococcus aureus ( S. aureus ) is the predominant causative pathogen across all OM subtypes, and its increasing antibiotic resistance has further complicated clinical management. Despite advances in antibiotic therapy and surgical debridement, treatment failure and disease recurrence remain unacceptably high. Emerging evidence suggests that these poor outcomes are largely attributed to the intricate host–pathogen interplay within the bone microenvironment, yet the underlying immunological mechanisms remain incompletely understood. This review provides a comprehensive overview of the epidemiological characteristics, classification, clinical features, pathophysiology, and current diagnostic and therapeutic strategies for OM, with a particular focus on host immune dysregulation in disease initiation and chronicity, elucidating the mechanisms underlying immunosuppressive niche formation and persistent bone destruction. We further dissect the multifaceted immune evasion strategies employed by S. aureus , including biofilm formation, intracellular persistence, and abscess barrier construction, which collectively drive infection chronicity and progressive bone destruction. By synthesizing recent advances in osteoimmunology, this review identifies critical knowledge gaps and proposes potential targeted immunomodulatory interventions, offering promising avenues to overcome conventional treatment limitations.