Evidence-based PET in musculoskeletal infectious and inflammatory diseases

Background: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) is an imaging modality capable of depicting metabolic activity associated with infectious and inflammatory processes. This systematic review aims to summarize and critically analyze the current evidence on the diagnostic performance and clinical impact of [18F]FDG PET/CT in major osteoarticular conditions, including prosthetic joint infection (PJI), diabetic foot infection (DFI), spondylodiscitis (SD), osteomyelitis (OM), and rheumatoid arthritis (RA). Methods: A comprehensive literature search was performed in PubMed/MEDLINE, Scopus, and Embase databases up to October 1, 2025, following PRISMA 2020 guidelines. Only original clinical studies evaluating the diagnostic role of [18F]FDG PET/CT in musculoskeletal infections and inflammation were included. Results: Seventy studies were selected. [18F]FDG PET/CT demonstrated high sensitivity and negative predictive value across all examined conditions, outperforming or complementing conventional imaging in complex or inconclusive cases. Furthermore, the modality's whole-body capability is invaluable for detecting occult metastatic infectious foci. Semiquantitative parameters such as SUVmax correlated with disease activity and treatment response. However, moderate specificity due to postoperative or aseptic inflammatory uptake and variability in acquisition protocols remain key limitations, emphasizing the need for standardized interpretation criteria. Conclusions: Current evidence supports [18F]FDG PET/CT as a reliable and versatile imaging modality for musculoskeletal infections and inflammatory disorders. Its integration into multimodal diagnostic workflows can enhance diagnostic confidence, guide tailored therapy, and improve patient management, although further standardization and prospective multicenter studies are warranted.