Department of Endocrinology, Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense C., Denmark.
J Clin Endocrinol Metab. 2013 Feb;98(2):571-80. doi: 10.1210/jc.2012-2972. Epub 2013 Jan 21.
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.
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.
This was a randomized, double-blind, 2-year trial.
The study was conducted at a private or institutional practice.
PARTICIPANTS included 214 postmenopausal women with low areal BMD.
The intervention included odanacatib 50 mg or placebo weekly.
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.
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.
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.
组织蛋白酶 K 抑制剂odanacatib 可增加绝经后低骨密度妇女的脊柱和髋部面积骨密度（BMD），并增加去卵巢猴的皮质厚度。
本研究旨在探讨odanacatib 对骨小梁和皮质骨的影响，并评估髋部和脊柱的估计骨强度。
这是一项随机、双盲、为期 2 年的试验。
该研究在私人或机构诊所进行。
214 名绝经后低面积 BMD 的女性参加了这项研究。
干预措施包括每周服用odanacatib 50mg 或安慰剂。
双能 X 射线吸收法（主要终点，1 年腰椎面积 BMD 变化）、骨转换标志物、定量计算机断层扫描（QCT）测量的体积 BMD、以及有限元分析估计的骨强度的变化。
与安慰剂相比，odanacatib 治疗 1 年后腰椎的面积 BMD 百分比增加了 3.5%（P<0.001）。与安慰剂相比，odanacatib 治疗 6 个月和 2 年后 1 型胶原 C 端肽的骨吸收标志物显著降低（P<0.001）。骨形成标志物原胶原 I N 端肽最初随着 odanacatib 而降低，但 2 年后与安慰剂无差异。6 个月后，odanacatib 治疗的女性脊柱的小梁体积 BMD 和估计压缩强度以及髋部的整体和小梁体积 BMD 和估计强度均有较大增加（P<0.001）。在股骨颈皮质包络中，骨矿物质含量、厚度、体积和横截面积也随着 odanacatib 治疗而从基线增加，与安慰剂相比差异有统计学意义（24 个月时 P<0.001）。两组的不良事件相似。
在 2 年的时间里，odanacatib 降低了骨吸收，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。
