Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial
Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial
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DOI：
10.1210/jc.2012-2972
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
de Papp, Anne E.
中科院分区：
文献类型：
--
作者：
Brixen, Kim;Chapurlat, Roland;de Papp, Anne E.
背景：Odanacatib 是一种组织蛋白酶 K 抑制剂，可增加绝经后妇女的脊柱和髋部区域骨矿物质密度 (BMD)，而绝经后妇女的骨密度和皮质厚度较低，而去势猴的骨密度和皮质厚度也较低。目的：本研究的目的是检查 odanacatib 对小梁骨和皮质骨区室的影响，并估计髋部和脊柱的强度。设计：这是一项随机、双盲、为期 2 年的试验。背景：该研究是在私人或机构诊所进行的。 参与者：参与者包括 214 名面积 BMD 较低的绝经后妇女。 干预：干预措施包括每周服用 odanacatib 50 毫克或安慰剂。 主要结果指标：通过双能 X 射线骨密度测定法测得的面积 BMD 变化（主要终点，腰椎 1 年面积 BMD 变化）、骨转换标记物、通过定量计算得出的体积 BMD测量了断层扫描 (QCT) 和通过有限元分析估计的骨强度。结果：第 1 年，odanacatib 组腰椎区域 BMD 相对于基线的百分比变化比安慰剂组高 3.5%（P < .001）。在 6 个月和 2 年时，与安慰剂相比，odanacatib 组的 1 型胶原骨吸收标志物 C 端肽显着降低 (P < .001)。骨形成标志物 I 型前胶原 N 端肽最初使用 odanacatib 降低，但 2 年后与安慰剂没有差异。 6 个月后，接受 odanacatib 治疗的女性的脊柱小梁体积 BMD 和估计抗压强度以及髋部整体和小梁体积 BMD 和估计强度有更大的增加 (P < .001)。与安慰剂相比，odanacatib 组股骨颈皮质包膜的骨矿物质含量、厚度、体积和横截面积也较基线有所增加（24 个月时 P < 0.001）。各组之间的不良经历相似。结论：2 年多来，odanacatib 减少了骨吸收，维持了骨形成，增加了面积和体积 BMD，并增加了髋部和脊柱的估计骨强度。 (临床内分泌代谢杂志 98: 571-580, 2013)
Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.Design: This was a randomized, double-blind, 2-year trial.Setting: The study was conducted at a private or institutional practice.Participants: Participants included 214 postmenopausal women with low areal BMD.Intervention: The intervention included odanacatib 50 mg or placebo weekly.Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P < .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P < .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P < .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P < .001 at 24 months). Adverse experiences were similar between groups.Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine. (J Clin Endocrinol Metab 98: 571-580, 2013)