Bauer D C
Department of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94105, USA.
Osteoporos Int. 2003 Jun;14(4):273-82. doi: 10.1007/s00198-002-1323-x. Epub 2003 May 8.
Recent studies suggest that the mevalonate pathway plays an important role in skeletal metabolism. HMG CoA reductase inhibitors ("statins"), which inhibit a key enzyme in the mevalonate pathway, are widely used for the treatment of hyperlipidemia. In vitro and animal studies demonstrate that statins stimulate the production of BMP-2, a potent regulator of osteoblast differentiation and activity, suggesting that statins may have an anabolic effect on bone. Statin use in most, but not all observational studies is associated with a reduced risk of fracture, particularly hip fracture, even after adjustment for the confounding effects of age, weight and other medication use. This beneficial effect has not been observed in clinical trials designed to assess cardiovascular endpoints. The effects of statins on bone mass and bone turnover are controversial, but increased bone mass and reduced bone turnover have been observed in controlled studies. Further studies of the skeletal effects of statins are needed, particularly their effects on surrogate markers such as bone mass, bone turnover, and microarchitecture, to determine the optimal formulation, dosing and route of administration. Clinical trials with fracture endpoints are needed before statins can be recommended as therapeutic agents for osteoporosis.
近期研究表明，甲羟戊酸途径在骨骼代谢中发挥重要作用。抑制甲羟戊酸途径中关键酶的HMG CoA还原酶抑制剂（“他汀类药物”）被广泛用于治疗高脂血症。体外和动物研究表明，他汀类药物可刺激骨形态发生蛋白-2（BMP-2）的产生，BMP-2是成骨细胞分化和活性的有效调节剂，这表明他汀类药物可能对骨骼有合成代谢作用。在大多数（但并非所有）观察性研究中，使用他汀类药物与骨折风险降低相关，尤其是髋部骨折，即使在对年龄、体重和其他药物使用的混杂效应进行调整之后亦是如此。在旨在评估心血管终点的临床试验中未观察到这种有益效果。他汀类药物对骨量和骨转换的影响存在争议，但在对照研究中已观察到骨量增加和骨转换减少。需要进一步研究他汀类药物对骨骼的影响，特别是它们对诸如骨量、骨转换和微结构等替代标志物的影响，以确定最佳配方、剂量和给药途径。在他汀类药物可被推荐作为骨质疏松症的治疗药物之前，需要进行有骨折终点的临床试验。
