Cedars-Sinai Medical Center and University of California, Los Angeles, CA, USA.
Osteoporos Int. 2012 Jan;23(1):351-63. doi: 10.1007/s00198-011-1691-1. Epub 2011 Jul 21.
In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated.
This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years.
A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N = 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers.
At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P < 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n = 1,324; femoral neck T-score ≤-3.0 and/or ≥ 1 moderate or severe or ≥ 2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P = 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P < 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P < 0.05) and was generally safe and well tolerated.
The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.
本研究评估了巴多昔芬治疗绝经后骨质疏松症超过 5 年的疗效和安全性。
共纳入 4216 例绝经后骨质疏松症患者，参加本为期 2 年的 3 年、随机、双盲、安慰剂对照、3 期试验的扩展部分。在核心研究（N=7492）中，受试者接受巴多昔芬 20 或 40 mg/天、雷洛昔芬 60 mg/天或安慰剂治疗。3 年后停用雷洛昔芬组；4 年后，接受巴多昔芬 40 mg 的受试者转换为巴多昔芬 20 mg。报告巴多昔芬 20 和 40/20 mg 与安慰剂的 5 年研究结果。终点包括新发椎体骨折（主要终点）和非椎体骨折，以及骨密度（BMD）和骨转换标志物的变化。
意向治疗人群中，巴多昔芬 20 mg（4.5%）和 40/20 mg（3.9%）的新发椎体骨折发生率显著低于安慰剂组（6.8%；P<0.05），相对风险分别降低 35%和 40%。各组非椎体骨折发生率相似。在高危女性亚组（n=1324；股骨颈 T 评分≤-3.0 和/或≥1 个中度或严重或≥2 个轻度椎体骨折）中，巴多昔芬 20 mg 降低了非椎体骨折风险（37%；P=0.06）；巴多昔芬 20 和 40/20 mg 的合并数据达到统计学意义（降低 34%；P<0.05）。巴多昔芬显著增加 BMD 并降低骨转换率（P<0.05），总体安全且耐受良好。
研究结果支持巴多昔芬对绝经后骨质疏松症妇女新椎体骨折和高危女性亚组非椎体骨折的持续抗骨折作用。
