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romosozumab与阿仑膦酸盐预防骨质疏松妇女骨折的比较研究
Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis


Kenneth G. Saag ... 妇产科和儿科 • 2017.10.12
相关阅读
• 为了预防骨折,仅治疗患骨质疏松症的女性可能还不够 • 骨密度低和骨质疏松的处理

摘要


背景

romosozumab是一种单克隆抗体,可与骨硬化蛋白结合并抑制该蛋白,促进骨形成并减少骨重吸收。

 

方法

我们招募了4,093例患骨质疏松和脆性骨折的绝经后妇女,并以1∶1的比例随机分组;在设盲的情况下,接受皮下注射romosozumab(210 mg,每月1次)或口服阿仑膦酸盐(70 mg,每周1次)治疗,共12个月,随后两组均接受开放标签的阿仑膦酸盐治疗。主要终点包括:24个月时新发椎体骨折的累积发生率,以及初步分析时(≥330例确诊临床骨折后)临床骨折(非椎体和症状性椎体骨折)的累积发生率。次要终点包括初步分析时非椎体和髋部骨折的发生率。严重的心血管不良事件、下颌骨坏死和非典型股骨骨折需要加以认定。

 

结果

我们观察到,在24个月内,与阿仑膦酸盐-阿仑膦酸盐组(11.9%[2,047例患者中有243例患者出现骨折])相比,romosozumab-阿仑膦酸盐组中新发的椎体骨折(6.2%[2,046例患者中有127例骨折])的风险降低48%(P<0.001)。在romosozumab-阿仑膦酸盐组中,2,046例患者中有198例出现临床骨折(9.7%),而在阿仑膦酸盐-阿仑膦酸盐组中,2,047例患者中有266例出现临床骨折(13.0%),这代表了romosozumab治疗可使骨折风险降低27%(P<0.001)。与阿仑膦酸盐-阿仑膦酸盐组相比,romosozumab-阿仑膦酸盐组中非椎体骨折的风险降低19%(2,047例患者中有217例骨折[10.6%] vs. 2,046例患者中有178例骨折[8.7%];P=0.04);髋部骨折的风险降低38%(2,047例患者中有66例骨折[3.2%] vs. 2,046例患者中有41例骨折[2.0%];P=0.02)。两组间的总体不良事件以及严重不良事件较为平衡。在第1年期间,romosozumab组中确切认定的严重心血管不良事件发生率高于阿仑膦酸盐组(2,040例患者中有50例[2.5%] vs. 2,014例患者中有38例[1.9%])。在开放标签的阿仑膦酸盐治疗期间,我们观察到下颌骨坏死(romosozumab-阿仑膦酸盐组和阿仑膦酸盐-阿仑膦酸盐组各1例)和非典型股骨骨折(分别有2例和4例)的认定事件。

 

结论

在患骨质疏松并且骨折风险较高的绝经后妇女中,与阿仑膦酸盐单独治疗相比,romosozumab治疗12个月并继之以阿仑膦酸盐治疗,可显著降低骨折风险(由安进和其他公司资助;ARCH在ClinicalTrials.gov注册号为NCT01631214)。





作者信息

Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mattias Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas Grauer, M.D.
From the University of Alabama, Birmingham (K.G.S.); Amgen, Thousand Oaks, CA (J.P., J.M., M.F., A.G.); University of Florence, Florence, Italy (M.L.B.); McGill University, Montreal (A.C.K.); University of Gothenburg and Sahlgrenska University Hospital, Mölndal, Sweden (M.L.); Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France (T.T.); and UCB Pharma, Brussels (P.D.M.). Address reprint requests to Dr. Saag at the Division of Clinical Immunology and Rheumatology, University of Alabama, Faculty Office Tower, Suite 820, 510 20th St. South, Birmingham, AL 35294-3408.

 

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