Bauer Douglas C, Mundy Greg R, Jamal Sophie A, Black Dennis M, Cauley Jane A, Ensrud Kristine E, van der Klift Marjolein, Pols Huibert A P
Department of Medicine, University of California, San Francisco 94105, USA.
Arch Intern Med. 2004 Jan 26;164(2):146-52. doi: 10.1001/archinte.164.2.146.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for the treatment of hyperlipidemia, and recent in vitro and animal data suggest that statins promote bone formation and increase bone strength.
To determine whether statin use is associated with a reduced risk for fracture, we analyzed statin use and fracture rates in 4 large prospective studies (the Study of Osteoporotic Fractures, the Fracture Intervention Trial, the Heart and Estrogen/Progestin Replacement Study, and the Rotterdam Study). We searched MEDLINE through January 2002 and abstracts from major scientific meetings and performed a cumulative meta-analysis of published and unpublished observational studies and clinical trials. The meta-analysis included 8 observational studies and 2 clinical trials that reported statin use and documented fracture outcomes.
After adjustment for multiple factors, including age, body mass index, and estrogen use, we found a trend toward fewer hip fractures (relative hazards [RHs], 0.19-0.62) and, to a lesser extent, nonspine fractures (RHs, 0.49-0.95) among statin users in each of the 4 prospective studies. The meta-analysis of observational studies was consistent with these findings. The summary odds ratio (OR) for statin use and hip fracture was 0.43 (95% confidence interval [CI], 0.25-0.75), whereas that for nonspine fracture was 0.69 (95% CI, 0.55-0.88). The meta-analysis of clinical trial results did not support a protective effect with statin use for hip fracture (summary OR, 0.87; 95% CI, 0.48-1.58) or nonspine fracture (OR, 1.02; 95% CI, 0.83-1.26).
Observational studies suggest that the risk for hip and nonspine fractures is lower among older women taking statin medications for hyperlipidemia, but post hoc analyses of cardiovascular trials do not. Controlled trials specifically designed to test the effect of statins on skeletal metabolism and fracture are needed.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）被广泛用于治疗高脂血症，最近的体外和动物实验数据表明，他汀类药物可促进骨形成并增加骨强度。
为了确定使用他汀类药物是否与降低骨折风险相关，我们分析了4项大型前瞻性研究（骨质疏松性骨折研究、骨折干预试验、心脏与雌激素/孕激素替代研究以及鹿特丹研究）中的他汀类药物使用情况和骨折发生率。我们检索了截至2002年1月的MEDLINE以及主要科学会议的摘要，并对已发表和未发表的观察性研究及临床试验进行了累积荟萃分析。该荟萃分析纳入了8项观察性研究和2项报告了他汀类药物使用情况及记录了骨折结局的临床试验。
在对包括年龄、体重指数和雌激素使用情况等多种因素进行调整后，我们发现，在这4项前瞻性研究的每一项中，他汀类药物使用者发生髋部骨折的数量有减少趋势（相对风险[RHs]为0.19 - 0.62），非脊柱骨折数量减少趋势相对较小（RHs为0.49 - 0.95）。观察性研究的荟萃分析与这些结果一致。使用他汀类药物与髋部骨折的汇总比值比（OR）为0.43（95%置信区间[CI]为0.25 - 0.75），而非脊柱骨折的汇总比值比为0.69（95% CI为0.55 - 0.88）。临床试验结果的荟萃分析并不支持使用他汀类药物对髋部骨折（汇总OR为0.87；95% CI为0.48 - 1.58）或非脊柱骨折（OR为1.02；95% CI为0.83 - 1.26）有保护作用。
观察性研究表明，服用他汀类药物治疗高脂血症的老年女性发生髋部和非脊柱骨折的风险较低，但心血管试验的事后分析结果并非如此。需要专门设计对照试验来测试他汀类药物对骨骼代谢和骨折的影响。
