Oregon Osteoporosis Center, Portland, OR, USA.
Australian Catholic University, Melbourne, Australia.
J Bone Miner Res. 2018 Aug;33(8):1397-1406. doi: 10.1002/jbmr.3452. Epub 2018 May 22.
Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤-2.0 and ≥-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
在 12 个月期间，罗莫佐单抗增加了骨形成并减少了骨吸收，导致骨密度（BMD）低的绝经后妇女的 BMD 增加（NCT00896532）。在此，我们报告了一项研究扩展，评估了罗莫佐单抗 24 个月的治疗、罗莫佐单抗停药、阿仑膦酸钠后罗莫佐单抗以及罗莫佐单抗后地舒单抗的情况。年龄在 55 至 85 岁之间的绝经后妇女，腰椎（LS）、总髋（TH）或股骨颈 T 评分≤-2.0 和≥-3.5，入组并随机分配至安慰剂、罗莫佐单抗五种方案之一（70mg、140mg、210mg 每月[QM]；140mg Q3M；210mg Q3M）治疗 24 个月，或开放标签阿仑膦酸钠治疗 12 个月后罗莫佐单抗 140mg QM 治疗 12 个月。符合条件的参与者随后在原始治疗组内以 1:1 的比例重新随机分配至安慰剂或地舒单抗 60mg Q6M 治疗 12 个月。评估了第 24 和 36 个月时从基线的 BMD 和骨转换标志物（BTM）的百分比变化以及安全性。最初随机分配至罗莫佐单抗、安慰剂或阿仑膦酸钠的 364 名参与者中，315 名完成了 24 个月的治疗，248 名完成了扩展。罗莫佐单抗在第 24 个月时明显增加了 LS 和 TH 的 BMD，其中罗莫佐umab 210mg QM 观察到的增益最大（LS=15.1%；TH=5.4%）。转为地舒单抗的接受罗莫佐单抗的女性继续获得 BMD，而安慰剂则使 BMD 恢复到治疗前水平。在罗莫佐单抗 210mg QM 中，骨形成标志物 P1NP 在治疗开始后最初增加，然后在第 12 个月逐渐降至基线以下，在第 24 个月仍低于基线；骨吸收标志物β-CTX 在治疗后迅速下降，在第 24 个月仍低于基线。转为地舒单抗进一步降低了两种 BTM，而转为安慰剂后，P1NP 恢复到基线，β-CTX 升高超过基线。不良事件在第 36 个月时在治疗组之间保持平衡。这些数据表明，罗莫佐单抗的治疗效果在停药后是可逆的，并进一步增强了地舒单抗的效果。
