Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
Department of Nuclear Medicine, Kawasaki Medical School, Okayama 701-0952, Japan.
J Clin Endocrinol Metab. 2022 Sep 28;107(10):e4222-e4231. doi: 10.1210/clinem/dgac486.
Abaloparatide reduced fracture risk in postmenopausal women with osteoporosis in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE). Its effect in Japanese patients remains unexamined.
This work aimed to determine the efficacy and safety of abaloparatide in increasing bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk.
This was a randomized, double-blind, placebo-controlled study conducted in Japan. Postmenopausal women and men with osteoporosis with high fracture risk were given daily subcutaneous 80 µg abaloparatide or placebo for 78 weeks (18 months). The primary end point was percentage change in lumbar spine (LS) BMD from baseline at the last visit. Secondary end points included time-course changes in LS, total hip (TH), and femoral neck (FN) BMDs and bone turnover markers, and cumulative number of fractures.
Abaloparatide increased LS, TH, and FN BMDs (mean [95% CI]) by 12.5% (10.3%-14.8%; P < .001), 4.3% (3.3%-5.3%), and 4.3% (2.9%-5.6%), respectively, vs placebo. Serum procollagen type I N-terminal propeptide increased rapidly to ~ 140% above baseline at 6 weeks and gradually decreased but was approximately 25% higher than baseline at 78 weeks. Serum carboxy-terminal cross-linking telopeptide of type I collagen gradually increased to 50% above baseline at 24 weeks and decreased gradually to the placebo-group level from 60 weeks. Four vertebrae of 3 participants in the placebo group, but none in the abaloparatide group, developed new vertebral fractures. The safety profile was similar to that in the ACTIVE study.
In Japanese patients with postmenopausal and male osteoporosis with high fracture risk, abaloparatide for 78 weeks robustly increased LS, TH, and FN BMDs, suggesting a similar efficacy in Japanese patients vs the ACTIVE study population.
在 Abaloparatide Comparator Trial In Vertebral Endpoints（ACTIVE）中，阿巴洛肽可降低绝经后骨质疏松症女性的骨折风险。其在日本患者中的疗效仍有待研究。
本研究旨在确定阿巴洛肽对日本高骨折风险骨质疏松症患者增加骨密度（BMD）的疗效和安全性。
这是一项在日本进行的随机、双盲、安慰剂对照研究。高骨折风险的绝经后妇女和男性骨质疏松症患者每日接受皮下注射 80μg 阿巴洛肽或安慰剂，共 78 周（18 个月）。主要终点是末次访视时腰椎（LS）BMD 相对于基线的百分比变化。次要终点包括 LS、全髋（TH）和股骨颈（FN）BMD 及骨转换标志物的时间变化以及骨折累计发生率。
阿巴洛肽使 LS、TH 和 FN BMD 分别增加 12.5%（10.3%-14.8%；P<0.001）、4.3%（3.3%-5.3%）和 4.3%（2.9%-5.6%），与安慰剂相比。血清Ⅰ型前胶原氨基端前肽迅速增加至基线以上约 140%，在 6 周时达到高峰，然后逐渐下降，但在 78 周时仍比基线高约 25%。血清Ⅰ型胶原羧基末端交联肽逐渐增加至基线以上 50%，在 24 周时达到高峰，然后逐渐下降至与安慰剂组水平相当。安慰剂组有 3 名患者的 4 个椎体发生新的椎体骨折，而阿巴洛肽组无患者发生。安全性特征与 ACTIVE 研究相似。
在日本高骨折风险的绝经后和男性骨质疏松症患者中，阿巴洛肽治疗 78 周可显著增加 LS、TH 和 FN BMD，表明其疗效在日本患者与 ACTIVE 研究人群相似。
