Chan M H, Mak T W, Chiu R W, Chow C C, Chan I H, Lam C W
Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong.
J Clin Endocrinol Metab. 2001 Sep;86(9):4556-9. doi: 10.1210/jcem.86.9.8001.
Animal studies, experimental models on cell lines, and epidemiological case-control studies have all suggested the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have a beneficial effect on bone metabolism. However, all epidemiological studies are not prospective in nature and based on either measurement of bone mineral density or fracture risk. They also differ in recruitment criteria, definition of statin exposure, and outcome assessment. We performed a first prospective study using specific biochemical bone markers on 17 hypercholesterolaemic non-osteoporotic subjects treated with a therapeutic dose of simvastatin 20 mg daily for 4 weeks. Our results show that serum osteocalcin concentration increased significantly (p-value < 0.05) 4 weeks after therapy, whereas other bone markers including serum bone-specific alkaline phosphatase activity, urine deoxypyridinoline, and urine cross-linked N-telopeptides of type I collagen did not show any significant changes. Our data support that simvastatin causes a beneficial effect on bone metabolism as reflected by an increase in serum osteocalcin concentration. This added beneficial effect of statins on bone metabolism could potentially allow statins to become the first effective anabolic agent for the treatment of osteoporosis. We urge that priority should be given to a randomised controlled study to re-evaluate this group of drugs.
动物研究、细胞系实验模型以及流行病学病例对照研究均表明，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂可能对骨代谢具有有益作用。然而，所有流行病学研究本质上并非前瞻性研究，且并非基于骨密度测量或骨折风险评估。它们在招募标准、他汀类药物暴露的定义以及结局评估方面也存在差异。我们对17名高胆固醇血症非骨质疏松患者进行了一项前瞻性研究，这些患者每日接受20毫克辛伐他汀治疗剂量治疗4周，并使用特定的生化骨标志物进行检测。我们的结果显示，治疗4周后血清骨钙素浓度显著升高（p值<0.05），而其他骨标志物，包括血清骨特异性碱性磷酸酶活性、尿脱氧吡啶啉和尿I型胶原交联N-端肽均未显示任何显著变化。我们的数据支持辛伐他汀对骨代谢具有有益作用，这一点通过血清骨钙素浓度的升高得以体现。他汀类药物对骨代谢的这种额外有益作用可能会使他汀类药物成为治疗骨质疏松症的首个有效合成代谢药物。我们敦促应优先进行一项随机对照研究，以重新评估这组药物。
