Mechanisms and research progress of statins in osteoarthritis.

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease characterized predominantly by articular cartilage degeneration, synovial inflammation, subchondral bone remodeling, and progressive impairment of joint function. Its pathogenesis is multifactorial and involves several interrelated pathological processes, including chronic low-grade inflammation, oxidative stress, dysregulated extracellular matrix metabolism, chondrocyte senescence and apoptosis, and microcirculatory dysfunction. At present, OA management remains largely focused on symptomatic relief, and disease-modifying agents capable of effectively delaying or reversing structural disease progression remain unavailable. As established HMG-CoA reductase inhibitors, statins exert a range of pleiotropic biological effects beyond lipid lowering, including anti-inflammatory and antioxidant actions, immunomodulatory activity, enhancement of endothelial function, and regulation of bone metabolism. These effects are closely aligned with the central pathogenic mechanisms implicated in OA. However, whether statins exert disease-modifying effects in OA, as well as the mechanisms underlying such effects, has not been systematically elucidated. In addition, current evidence is derived predominantly from in vitro experiments and animal models, whereas clinical evidence remains limited and heterogeneous. This review aims to evaluate the potential disease-modifying effects of statins in OA. Specifically, it systematically summarizes their mechanisms of action in the synovium, cartilage, subchondral bone, and vascular-metabolic microenvironment, reviews evidence from basic and clinical studies, and discusses the principal limitations and knowledge gaps in the current literature. Available studies indicate that statins may confer protective effects on OA-related tissues by modulating key pathological processes, including inflammation, oxidative stress, extracellular matrix metabolism, and bone remodeling. Nevertheless, robust high-quality clinical evidence supporting the use of statins as a disease-modifying therapeutic strategy for OA is still lacking. Future well-designed randomized controlled trials, integrated with disease phenotyping and biomarker-based investigations, are warranted to further define the clinical relevance, optimal target populations, and therapeutic value of different statin types, doses, and routes of administration.