Therapeutic effects of statins on osteoarthritis: A review

Abstract

Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the β‐hydroxy β‐methylglutaryl‐CoA (HMG‐CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG‐CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin‐1β‐stimulation. Atorvastatin stimulates the STAT1‐caspase‐3 signaling pathway that was shown to be responsible for its anti‐inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

Assessing the causal associations of different types of statins use and knee/hip osteoarthritis: A Mendelian randomization study

“…Our study further supports the positive effects of statins in preventing OA. In particular, atorvastatin has been shown to protect against cartilage degeneration following IL-1β stimulation and elicit anti-inflammatory effects through the stimulation of the STAT1-caspase-3 signaling pathway [ 32 ]. Studies by Pathak et al demonstrated that atorvastatin can reduce the inflammatory response induced by monosodium iodoacetate in a rat joint model [ 8 ].In their study, Jiancongchen et al found that atorvastatin could suppress matrix degradation in rat nucleus pulposus cells induced by TNF-α [ 5 ].…”

Drug Repurposing: Therapeutic Role of Aripiprazole in the Cartilage Defect

“…Statins are commonly used to lower cholesterol levels by inhibiting 3-hydroxy-3methylglutaryl-CoA. However, they also have anti-in ammatory and antioxidant properties, which may bene t cartilage repair and regeneration 23,26,27 . This mechanism is bene cial in preventing cartilage degradation.…”

“…In recent years, drug repositioning-also known as drug repurposing, repro ling, rescue, redirecting, switching, or retaking-has emerged as a promising strategy for developing new treatments for various diseases, including osteoarthritis [14][15][16][17][18][19][20][21][22][23] . Drug repositioning involves the identi cation of existing or abandoned drugs that may have therapeutic potential for new indications 24 .…”

Hip and Knee Osteoarthritis in Patients with Chronic Myeloproliferative Neoplasms: A Cross-Sectional Study

“…More interestingly, the presence of sOA correlated with lower serum lipids, which could be explained with the influence of statin therapy, but also due to the high membrane uptake of cholesterol caused by an increased cell turnover in the bone marrow, potentially suggesting a more aggressive disease biology in MPN patients with OA [ 68 , 69 ]. Considering that statins may exert beneficial effects on both the osteoarticular system [ 70 ] and the MPN clone [ 71 , 72 ], additional studies are needed to unravel whether these compounds may also potentially have beneficial effects on OA development and progression in MPN patients.…”