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

• Published in: European journal of clinical investigation Vol. 51; no. 7; pp. e13534 - n/a
• Main Authors: Chamani, Sajad, Liberale, Luca, Mobasheri, Leila, Montecucco, Fabrizio, Al‐Rasadi, Khalid, Jamialahmadi, Tannaz, Sahebkar, Amirhossein
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.07.2021
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - drug effects; Alkaline Phosphatase - metabolism; Arteriosclerosis; Arthritis; Atherosclerosis; Biomedical materials; Biosynthesis; bone; Bone Density - drug effects; Bone diseases; Bone growth; Bone mineral density; Bone Morphogenetic Protein 2 - drug effects; Bone Morphogenetic Protein 2 - metabolism; Bone morphogenetic proteins; Bone turnover; Cell differentiation; Cell Differentiation - drug effects; Cerebral infarction; Cholesterol; Clinical trials; Coenzyme A; Collagen (type I); Collagen Type I - drug effects; Collagen Type I - metabolism; Collagenase; Collagenases - drug effects; Collagenases - metabolism; Complications; Differentiation (biology); Glucocorticoids; Glucocorticoids - metabolism; Growth factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; In vivo methods and tests; Literature reviews; Low density lipoprotein; Metabolism; Myocardial infarction; osteoblast; Osteoblastogenesis; Osteoblasts - drug effects; osteoclast osteogenesis; Osteoclastogenesis; Osteoclasts - drug effects; Osteogenesis; Osteogenesis - drug effects; Osteoporosis; Osteosynthesis; Protein turnover; Reductases; Risk reduction; Statins; Transforming Growth Factor beta - drug effects; Transforming Growth Factor beta - metabolism; osteoclast osteogenesis; bone; osteoblast; statins
• ISSN: 0014-2972; 1365-2362; 1365-2362
• DOI: 10.1111/eci.13534

Background 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 ischaemic 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. Design The most relevant papers on the bone‐related ‘pleiotropic’ effects of statins were selected following literature search in databases and were reveiwed. Results 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. Conclusion This review summarizes the literature exploring bone‐related ‘pleiotropic’ effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis.