Revisiting the Subtle Relationship Between Metabolic Syndrome and Osteoarthritis

Osteoarthritis (OA) is a common disabling joint disorder traditionally attributed to mechanical wear. Emerging evidence shows that metabolic syndrome (MetS) and its components-obesity, hypertension, hyperglycemia, and dyslipidemia-are closely associated with OA onset and progression, suggesting that OA also has a metabolic-inflammatory nature.

This review highlights mechanisms linking each MetS component to OA. Obesity contributes not only by increasing joint load but also through adipokines such as leptin, resistin, and visfatin, which activate inflammatory pathways and promote cartilage degradation and synovitis. Hypertension may worsen OA via joint ischemia, oxidative stress, and renin-angiotensin system activation. Hyperglycemia damages cartilage and ligaments by promoting advanced glycation end product accumulation and oxidative stress. Dyslipidemia influences OA through cholesterol deposition and inflammatory responses. Metabolic inflammation and immunometabolic reprogramming further drive OA progression.

MetS and OA are interconnected through mechanical stress, adipokine activity, inflammatory signaling, and metabolic dysregulation. Future studies should clarify how MetS affects pain, subchondral bone remodeling, and other OA phenotypes, aiding the development of individualized, metabolism-targeted strategies for early intervention and comprehensive OA management.