Abstract
Background and Objectives: Osteomyelitis is a progressive bone infection requiring a combination of antimicrobial and anti-inflammatory therapies. While antibiotics remain the cornerstone of treatment, the role of NSAIDs and steroidal anti-inflammatory drugs (SAIDs) in modulating inflammation and improving clinical outcomes warrants further investigation. This systematic review evaluates the effectiveness and safety of combined antibiotic and NSAID/SAID therapy in osteomyelitis, aligning treatment strategies with disease stage and pathogenesis. Materials and Methods: A systematic search was conducted in Web of Science, Scopus, and PubMed from July 2024 to November 2024, following PRISMA and CARE guidelines. The studies were selected based on detailed pharmacological data, treatment outcomes, and follow-up analysis. The risk of bias was assessed using the Critical Appraisal Skills Programmed (CASP) tool. Statistical reliability between coders was evaluated using Cohen's kappa coefficient (κ = 0.636-0.909) and intra-class correlation coefficient (ICC = 1.0). Results: Four case studies, representing acute, chronic, recurrent, and SAPHO syndrome-associated osteomyelitis, demonstrated variable responses to combined therapy. Antibiotics alone were effective in acute cases, while NSAIDs/SAIDs significantly contributed to inflammatory control in chronic and immune-mediated osteomyelitis. Glucocorticoids (e.g., prednisolone, methylprednisolone) showed efficacy in reducing systemic inflammation, with no major adverse effects reported. The transition from intravenous to oral antibiotic therapy was observed in all cases, ensuring sustained infection control. Conclusions: This review highlights the critical role of NSAIDs/SAIDs in complementing antibiotic therapy, particularly in chronic and refractory osteomyelitis. Stage-specific pharmacological interventions improve treatment outcomes, and future research should explore bisphosphonates and immunomodulatory agents to refine therapeutic approaches. These findings reinforce the need for personalized osteomyelitis management based on pathogenesis, microbiology, and disease progression.