Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.
Department of Immunology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Eur J Clin Invest. 2021 Jul;51(7):e13534. doi: 10.1111/eci.13534. Epub 2021 Mar 11.
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.
The most relevant papers on the bone-related 'pleiotropic' effects of statins were selected following literature search in databases and were reveiwed.
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 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.
他汀类药物是 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂，可阻断肝细胞中的胆固醇生物合成，从而导致低密度脂蛋白（LDL）受体增加，从而增强对动脉粥样硬化性 LDL-胆固醇（LDL-C）的摄取和清除。因此，他汀类药物降低了发生动脉粥样硬化及其急性并发症（如急性心肌梗死和缺血性中风）的风险。除了降低 LDL-C 的作用外，他汀类药物还具有其他所谓的多效性作用。其中，调节骨细胞分化和功能的能力，并对成骨合成因素发挥直接作用。具体来说，早期研究表明他汀类药物可引起体外和体内成骨分化。
根据文献数据库的检索，选择了与他汀类药物的骨相关“多效性”作用最相关的论文进行综述。
他汀类药物增加了许多参与骨代谢的介质的表达，包括骨形态发生蛋白-2（BMP-2）、糖皮质激素、转化生长因子-β（TGF-β）、碱性磷酸酶（ALP）、I 型胶原和胶原酶-1。因此，它们通过调节成骨细胞和破骨细胞的分化来增强骨形成并改善骨密度。
本文综述了探讨他汀类药物与骨相关“多效性”作用的文献，并提出了该类药物在骨组织中的合成代谢作用。因此，目前的知识鼓励进一步的临床试验来评估他汀类药物在治疗骨疾病（如关节炎和骨质疏松症）方面的治疗潜力。
