Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis A Randomized Clinical Trial
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DOI：
10.1001/jama.2016.11136
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发表时间：
2016-08-16
影响因子：
120.7
通讯作者：
Christiansen, Claus
中科院分区：
文献类型：
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作者：
Miller, Paul D.;Hattersley, Gary;Christiansen, Claus
重要性：预防骨质疏松性骨折需要额外的治疗方法。阿巴拉蒂是甲状旁腺激素1型受体的选择性激活剂。目的比较阿巴拉肽80微克与安慰剂预防有骨质疏松性骨折风险的绝经后妇女新的椎体骨折的有效性和安全性。设计、设置和参与者在10个国家的28个地点进行了3期的阿巴拉肽对照试验(ACTIVE)，双盲，随机对照试验(RCT)。符合条件的绝经后妇女，腰椎或股骨颈骨密度(BMD)T评分-5.0，且在过去5年内有放射学证据<gt；=2轻度或<gt；=1中度腰椎或胸椎骨折或有低创伤非椎体骨折病史。符合骨折标准和T分-2.0和-5.0的绝经后妇女(65岁)，或没有骨折标准和T分-5.0的妇女可以参加试验。介入治疗中，每天皮下注射安慰剂(n=821)、阿巴拉定(n=824)或开放标签的特瑞帕替德(n=818)，20µg(n=818)。主要终点是abaloparatide组和安慰剂组中有新的椎体骨折的参与者的百分比。样本量被设置为检测治疗组之间4%的差异(57%的风险降低)。次要终点包括接受阿巴拉定治疗的受试者与安慰剂受试者在全髋关节、股骨颈和腰椎的骨密度变化，以及首次发生非椎体骨折的时间。结果在2463名女性(平均年龄69岁，范围49-86)中，1901名女性完成了这项研究。与安慰剂组相比，积极治疗组中新的形态测量椎体骨折发生的频率较低。非椎体骨折的Kaplan-Meier估计事件发生率用阿巴拉替德比安慰剂低。服用阿巴拉定的患者骨密度增加幅度大于安慰剂(均为P<；.001)。服用abaloparatide(3.4%)和teriparatide(6.4%)的高钙血症发生率较低(风险差异[RD]，-2.96[95%CI，-5.12至-0.87]；P=.006)。[图表]结论和相关性：在绝经后骨质疏松的妇女中，与安慰剂相比，皮下使用abaloparatide降低了18个月后新的椎体和非椎体骨折的风险。需要进一步的研究来了解RD的临床重要性，阿巴拉肽治疗的风险和益处，以及阿巴拉肽与其他骨质疏松症治疗方法的疗效。
IMPORTANCE Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.OBJECTIVE To determine the efficacy and safety of abaloparatide, 80 mu g, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.DESIGN, SETTING, AND PARTICIPANTS The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score -5.0 at the lumbar spine or femoral neck and radiological evidence >= 2 mild or >= 1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score >-2.0 and >-5.0 or without fracture criteria and a T score -5.0 could enroll.INTERVENTIONS Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 mu g (n = 824); or open-label teriparatide, 20 mu g (n = 818) for 18 months.MAIN OUTCOMES AND MEASURES Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.RESULTS Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], -2.96 [95% CI, -5.12 to -0.87]; P = .006).[GRAPHICS]CONCLUSIONS AND RELEVANCE Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.