Uzzan Bernard, Cohen Régis, Nicolas Patrick, Cucherat Michel, Perret Gérard-Yves
AP-HP, Laboratoire de Pharmacologie, Hôpital Avicenne, 125 route de Stalingrad, 93009-Bobigny, France.
Bone. 2007 Jun;40(6):1581-7. doi: 10.1016/j.bone.2007.02.019. Epub 2007 Mar 1.
Statins inhibit HMG-CoA reductase, preventing synthesis of mevalonate but also of isoprenoids, which affect osteoclast activity. Amino-bisphosphonates share this effect. In vitro and in vivo, statins show convincing anabolic and anti-resorptive bone effects. However, in a clinical meta-analysis (MA), they did not prevent hip fractures.
Our meta-analysis studied the impact of statins on bone mineral density (BMD) at various sites and compared the effects of lipophilic and more hydrophilic statins.
Our PubMed and Embase queries using two keywords (statins, BMD) were updated to October 2006.
Two readers independently collected BMDs from studies.
Twenty-one studies, mostly observational (three randomized controlled trials and one pseudo-randomized study), were assessed. Two studies were excluded (no control groups). Three studies could not be analyzed. The sixteen studies analyzed mainly included postmenopausal osteopenic women (2971 patients under statins). Statins significantly increased BMD at total hip (TH) and femoral neck (FN). Effect sizes (ESs) were modest: 0.21 at TH (95% confidence interval [CI]: 0.16-0.25) and 0.20 at FN (CI: 0.08-0.28). Among women, statins acted similarly (ES: 0.20 for TH and 0.18 for FN; CI: 0.14-0.25 and 0.06-0.31 respectively); lipophilic statins (simvastatin, lovastatin) almost entirely caused this effect, at both TH (ES: 0.20; CI: 0.15-0.26) and FN (ES: 0.22; CI: 0.06-0.37).
Our findings of modest but statistically significant beneficial effects of statins on hip BMD should promote large double-blind randomized controlled trials on their bone effects, in view of their major beneficial cardiovascular effects with excellent safety profile.
他汀类药物抑制3-羟基-3-甲基戊二酰辅酶A还原酶，不仅阻止甲羟戊酸的合成，还阻止类异戊二烯的合成，而类异戊二烯会影响破骨细胞活性。氨基双膦酸盐也有此作用。在体外和体内，他汀类药物显示出令人信服的促合成和抗骨吸收的骨骼效应。然而，在一项临床荟萃分析中，它们并未预防髋部骨折。
我们的荟萃分析研究了他汀类药物对不同部位骨密度（BMD）的影响，并比较了亲脂性他汀类药物和亲水性更强的他汀类药物的效果。
我们使用两个关键词（他汀类药物、骨密度）对PubMed和Embase进行的检索更新至2006年10月。
两名读者独立从研究中收集骨密度数据。
评估了21项研究，大多为观察性研究（三项随机对照试验和一项半随机研究）。两项研究被排除（无对照组）。三项研究无法进行分析。分析的16项研究主要纳入了绝经后骨质减少的女性（2971例服用他汀类药物的患者）。他汀类药物显著增加了全髋（TH）和股骨颈（FN）的骨密度。效应大小适中：全髋处为0.21（95%置信区间[CI]：0.16 - 0.25），股骨颈处为0.20（CI：0.08 - 0.28）。在女性中，他汀类药物的作用相似（全髋效应大小为0.20，股骨颈为0.18；CI分别为0.14 - 0.25和0.06 - 0.31）；亲脂性他汀类药物（辛伐他汀、洛伐他汀）几乎完全导致了这种效应，在全髋（效应大小为0.20；CI：0.15 - 0.26）和股骨颈（效应大小为0.22；CI：0.06 - 0.37）处均如此。
鉴于他汀类药物具有主要的有益心血管效应且安全性良好，我们发现他汀类药物对髋部骨密度有适度但具有统计学意义的有益作用，这应促使开展关于其骨骼效应的大型双盲随机对照试验。
