Helen Hayes Hospital, West Haverstraw, NY, USA.
College of Physician and Surgeons, Columbia University, New York, NY, USA.
J Bone Miner Res. 2018 Jul;33(7):1219-1226. doi: 10.1002/jbmr.3427. Epub 2018 May 17.
Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p < 0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
罗莫佐单抗是一种具有双重作用的成骨药物，既能增加骨形成，又能减少骨吸收。在 FRActure 研究中，绝经后骨质疏松症妇女（FRAME）接受罗莫佐单抗 210mg sc 或安慰剂每月 1 次，共 12 个月，然后两组均接受地舒单抗 60mg sc 每 6 个月 1 次，共 12 个月。罗莫佐单抗治疗 1 年可分别使脊柱和髋部骨密度增加 13%和 7%，并降低椎体和临床骨折发生率，且在转换为地舒单抗后 24 个月持续降低骨折风险。在此，我们通过量化不同程度的患者应答比例，进一步描述了罗莫佐单抗的骨密度增加情况；报告了 2 年研究期间从基线开始的平均 T 评分变化，并将这些结果与长期使用地舒单抗在骨质疏松症骨折减少评估每 6 个月 1 次（FREEDOM）及其扩展研究中观察到的骨密度增加进行对比；并评估了第 2 年所有患者接受地舒单抗时的骨折发生率。在 7180 名患者中（n=3591 名安慰剂，n=3589 名罗莫佐单抗），与安慰剂相比，大多数接受罗莫佐单抗治疗的患者在第 12 个月时脊柱（96%）和髋部（78%）的骨密度较基线有 ≥3%的增加（脊柱：22%，髋部：16%）。对于罗莫佐单抗患者，12 个月时脊柱和髋部的平均绝对 T 评分分别增加 0.88 和 0.32（安慰剂：0.03 和 0.01），24 个月时增加 1.11 和 0.45（安慰剂至地舒单抗：0.38 和 0.17），2 年的增加量接近 7 年连续使用地舒单抗的效果。在第 1 年接受罗莫佐单抗治疗的患者与接受安慰剂治疗的患者相比，第 2 年的椎体骨折明显减少（相对减少 81%；p<0.001），在其他骨折类别中也持续观察到骨折减少。数据支持在向抗吸收治疗转换之前，用罗莫佐单抗重建骨骼基础的临床获益。© 2018 作者。由 Wiley Periodicals, Inc. 出版的《骨与矿物研究杂志》
