Statin in Clinical and Preclinical Knee Osteoarthritis-What E vidence Exists for Future Clinical Use?-A Literature Review

Statins are used to lower serum cholesterol. Recent preclinical and clinical research focuses on articular cartilage regeneration aspects of statin. This review summarizes the effects of statins on knee osteoarthritis (OA).Published preclinical and clinical literature till November 2021 were searched in PubMed and PubMed Central databases. Articles not written in English, not relevant for the review, and unpublished evidence were excluded. Finally, 27 papers were reviewed and presented in the study.A total of 27 articles have been included-13 clinical and 14 preclinical studies. Preclinical studies showed statin-induced chondroprotective effects; these included in vitro studies on human or animal-derived degenerated articular cartilage as well as OA animal models. Chondroprotective effects of statins are thought to mediate by inhibiting the Wnt/β-catenin signaling pathway, preventing synovial inflammation, and inhibiting catabolic-stress-induced aging of cartilage. Preclinical study outcomes were based on biochemical, macroscopic, and microscopic (histology) assessments and seemed promising in cartilage regeneration. In the 13 clinical studies, the effect of statins on human OA is inconclusive: some showing improvement of OA symptoms, and others depict signs of aggravation and radiological progression. No randomized controlled trial (RCT) has tested the efficacy of intra-articular statins in clinical knee OA, and it seems feasible to avoid oral statinassociated severe adverse effects.There are no arguments to recommend oral statins in clinical OA-knee. An RCT testing the efficacy of oral statins in patients with OA knee was never done and still seems justified, as well as a prospective phase-II clinical trial for intra-articular statins in different types of OA.