Black Dennis M, Delmas Pierre D, Eastell Richard, Reid Ian R, Boonen Steven, Cauley Jane A, Cosman Felicia, Lakatos Péter, Leung Ping Chung, Man Zulema, Mautalen Carlos, Mesenbrink Peter, Hu Huilin, Caminis John, Tong Karen, Rosario-Jansen Theresa, Krasnow Joel, Hue Trisha F, Sellmeyer Deborah, Eriksen Erik Fink, Cummings Steven R
University of California, San Francisco, San Francisco, CA 94107, USA.
N Engl J Med. 2007 May 3;356(18):1809-22. doi: 10.1056/NEJMoa067312.
A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.
In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.
Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001).
A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.)
单次静脉输注唑来膦酸可降低绝经后骨质疏松症女性的骨转换并在12个月时改善骨密度。我们评估了每年输注唑来膦酸在3年期间对骨折风险的影响。
在这项双盲、安慰剂对照试验中，3889例患者（平均年龄73岁）在基线、12个月和24个月时被随机分配接受单次15分钟的唑来膦酸（5毫克）输注，3876例患者被分配接受安慰剂；对患者进行随访直至36个月。主要终点是新发椎体骨折（未同时服用骨质疏松症药物的患者）和髋部骨折（所有患者）。次要终点包括骨矿物质密度、骨转换标志物和安全性结果。
与安慰剂相比，唑来膦酸治疗在3年期间将形态计量学椎体骨折的风险降低了70%（唑来膦酸组为3.3%，安慰剂组为10.9%；相对风险，0.30；95%置信区间[CI]，0.24至0.38），并将髋部骨折的风险降低了41%（唑来膦酸组为1.4%，安慰剂组为2.5%；风险比，0.59；95%CI，0.42至0.83）。非椎体骨折、临床骨折和临床椎体骨折分别降低了25%、33%和77%（所有比较P<0.001）。唑来膦酸还与骨矿物质密度和骨代谢标志物显著改善相关。包括肾功能变化在内的不良事件在两个研究组中相似。然而，唑来膦酸组严重房颤的发生频率更高（50例对20例，P<0.001）。
在3年期间每年输注一次唑来膦酸可显著降低椎体、髋部和其他骨折的风险。（临床试验.gov编号，NCT00049829。）
