Effects of denosumab on bone mineral density and bone turnover in postmenopausal women
Effects of denosumab on bone mineral density and bone turnover in postmenopausal women
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DOI：
10.1210/jc.2007-2814
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发表时间：
2008-06-01
影响因子：
5.8
通讯作者：
Martin, Javier San
中科院分区：
文献类型：
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作者：
Bone, Henry G.;Bolognese, Michael A.;Martin, Javier San
背景：狄诺塞麦是一种针对核因子-κ B 配体受体激活剂的研究性全人单克隆抗体，核因子-κ B 配体是破骨细胞生成和破骨细胞存活的介质。 目的：本研究评估了狄诺塞麦在早期和后期低 BMD 绝经后妇女中增加骨矿物质密度 (BMD) 和降低骨转换标志物 (BTM) 的能力。 设计和背景：这项为期 2 年的随机、双盲、安慰剂对照研究受试者：受试者包括 332 名腰椎 BMD T 评分在 -1.0 至 -2.5 之间的绝经后女性。 干预措施：受试者被随机分配接受皮下注射狄诺塞麦（每 6 个月 60 毫克）或安慰剂。随机分组按绝经开始后的时间（5 年）进行分层。主要结果指标：主要终点是 24 个月时通过双能 X 射线骨密度测定法测得的腰椎 BMD 变化百分比。其他终点是通过定量计算机断层扫描得出的远端桡骨体积 BMD 的百分比变化；通过双能 X 射线骨密度测定法测定全髋关节、三分之一桡骨和全身的 BMD 百分比变化；髋关节结构分析； BTM 的百分比变化；结果：24 个月时，与安慰剂相比，狄诺塞麦显着增加了腰椎 BMD（6.5 对比 -0.6%；P < 0.0001），两个层面的结果相似。狄诺塞麦还显着增加了全髋关节、三分之一桡骨和全身的 BMD（与安慰剂相比，P < 0.0001）；桡骨远端体积 BMD 增加（P < 0.01）；改进的髋部结构分析参数；并显着抑制血清 C 端肽、抗酒石酸酸性磷酸酶 5b 和完整的 1 型前胶原 N 端前肽。两个研究组之间不良事件的总体发生率相似。结论：每年两次地诺塞麦可增加早期和晚期绝经后女性的 BMD 并降低 BTM。
Context: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappa B ligand, a mediator of osteoclastogenesis and osteoclast survival.Objective: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD.Design and Setting: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America.Participants: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5.Interventions: Subjects were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause ( 5 yr).Main Outcome Measures: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety.Results: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P < 0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups.Conclusions: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.