The role of statins in the differentiation and function of bone cells.

Chamani, Sajad; Liberale, Luca; Mobasheri, Leila; Montecucco, Fabrizio; Al-Rasadi, Khalid; Jamialahmadi, Tannaz; Sahebkar, Amirhossein

Statins are 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA( reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low-density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL-cholesterol (LDL-C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischemic stroke. Besides the LDL-C-lowering impact, statins also have other so-called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation. Statins increase the expression of many mediators involved in bone metabolism, including bone morphogenetic protein-2 (BMP-2), glucocorticoids, transforming growth factor-beta (TGF-β), alkaline phosphatase (ALP), type I collagen, and collagenase-1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation. This review article summarizes the literature exploring bone-related "pleiotropic" effects of statins and suggesting an anabolic role in the bone tissue for such a drug class. Accordingly, current knowledge encourages further clinical trials to assess their therapeutic potential in the treatment of bone disorders, such as arthritis and osteoporosis.