Romosozumab in Postmenopausal Women with Low Bone Mineral Density

作者：Michael R. McClung, Andreas Grauer, Steven Boonen, Michael A. Bolognese, Jacques P. Brown, Adolfo Díez‐Pérez, Bente Langdahl, Jean‐Yves Reginster, José Zanchetta, Scott M. Wasserman, Leonid Katz, Judy Maddox, Yuching Yang, Cesar Libanati, Henry G. Bone · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1305224 · 被引用次数：1254 · 研究领域：Bone health and osteoporosis research、Bone Metabolism and Diseases、Rheumatoid Arthritis Research and Therapies

BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS: All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip an...