Schlienger Raymond G, Meier Christoph R
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology, University Hospital, Basel, Switzerland.
Drugs Aging. 2003;20(5):321-36. doi: 10.2165/00002512-200320050-00002.
Osteoporosis affects a large number of people in industrialised countries. It has clinical and public-health impacts, most importantly due to subsequent fractures. Osteoporotic fractures are one of the most common causes of disability and are associated with enormous healthcare expenditure. The majority of existing treatment options for osteoporosis only inhibit bone resorption and prevent excessive bone loss but are not capable of stimulating bone formation. However, several recent in vitro and in vivo studies in animals demonstrated that HMG-CoA reductase inhibitors stimulate the production of bone morphogenetic protein (BMP-2), which is a potent regulating protein in osteoblast differentiation and activity. This suggests that HMG-CoA reductase inhibitors may have an anabolic effect on bones, making them a potentially interesting treatment option for osteoporosis. Additionally, several studies in humans showed that some HMG-CoA reductase inhibitors may have a beneficial effect on bone turnover and may lead to an increase in bone mineral density. Consequently, several observational studies tried to evaluate whether use of HMG-CoA reductase inhibitors is associated with a decreased risk of fractures. Even though not all results of these epidemiological studies, using different designs in different study populations, were entirely consistent, they provided substantial evidence that HMG-CoA reductase inhibitor use may decrease the bone fracture risk by approximately 50%. On the other hand, reanalysis of two randomised controlled trials of HMG-CoA reductase inhibitor therapy, designed to assess cardiovascular outcomes, could not show that patients treated with HMG-CoA reductase inhibitors had a lower fracture risk in comparison with placebo-treated patients. Therefore, to conclusively assess the potential of HMG-CoA reductase inhibitors in the prevention and treatment of osteoporosis, randomised controlled trials need to be performed to address this conflicting issue. Until the results of such trials are available, practitioners should prescribe the drugs that have been proven to reduce the risk of osteoporotic fractures.
骨质疏松症在工业化国家影响着大量人群。它具有临床和公共卫生影响，最重要的是会引发后续骨折。骨质疏松性骨折是导致残疾的最常见原因之一，且与巨额医疗费用相关。现有的大多数骨质疏松症治疗方案仅抑制骨吸收并防止过度骨质流失，但无法刺激骨形成。然而，近期多项针对动物的体外和体内研究表明，HMG - CoA还原酶抑制剂可刺激骨形态发生蛋白（BMP - 2）的产生，而BMP - 2是成骨细胞分化和活性中的一种强效调节蛋白。这表明HMG - CoA还原酶抑制剂可能对骨骼具有合成代谢作用，使其成为一种潜在的骨质疏松症治疗选择。此外，一些针对人类的研究表明，某些HMG - CoA还原酶抑制剂可能对骨转换有有益影响，并可能导致骨矿物质密度增加。因此，多项观察性研究试图评估使用HMG - CoA还原酶抑制剂是否与骨折风险降低相关。尽管这些在不同研究人群中采用不同设计的流行病学研究并非所有结果都完全一致，但它们提供了大量证据表明使用HMG - CoA还原酶抑制剂可使骨折风险降低约50%。另一方面，对两项旨在评估心血管结局的HMG - CoA还原酶抑制剂治疗随机对照试验的重新分析未能表明，与接受安慰剂治疗的患者相比，接受HMG - CoA还原酶抑制剂治疗的患者骨折风险更低。因此，为了最终评估HMG - CoA还原酶抑制剂在预防和治疗骨质疏松症方面的潜力，需要进行随机对照试验来解决这一矛盾问题。在获得此类试验结果之前，从业者应开具已被证明可降低骨质疏松性骨折风险的药物。
