Osteoarthritis: epidemiology, risk factors, molecular pathogenesis, therapeutic progress, and future perspectives

Osteoarthritis (OA) is a heterogeneous whole-joint disease and a leading cause of pain and disability worldwide. Its development and progression reflect complex interactions among ageing, genetic susceptibility, mechanical stress, inflammation, and metabolic dysfunction. This review integrates current knowledge of OA epidemiology, risk factors, molecular pathogenesis, and therapeutic advances, with particular emphasis on lipid metabolism as an emerging regulator of joint homeostasis. We introduce lipid metabolic coding as a conceptual framework describing how lipid-derived substrates and signals are processed in a context-dependent manner to influence cellular identity, stress responses, and inter-tissue communication. Altered fatty-acid metabolism, de novo lipogenesis, lipid-droplet turnover, cholesterol handling, and post-translational modifications may contribute to cartilage degeneration and whole-joint pathology. We further discuss four overlapping, potentially stage-dependent lipid-associated endotypes as testable models rather than established clinical classifications. Although experimental evidence identifies promising metabolic targets, their causal relevance and therapeutic utility in human OA remain incompletely defined. Integrating longitudinal clinical data with spatial multi-omics and functional validation may clarify these mechanisms and support the development of more precisely targeted, disease-modifying therapies.