罗莫佐单抗治疗绝经后低骨密度妇女。
Romosozumab in postmenopausal women with low bone mineral density.
机构信息
From the Oregon Osteoporosis Center, Portland (M.R.M.); Amgen, Thousand Oaks, CA (A.G., S.M.W., L.K., J.M., Y.-C.Y., C.L.); Leuven University, Leuven (S.B.), and University of Liege, Liege (J.-Y.R.) - both in Belgium; Bethesda Health Research Center, Bethesda, MD (M.A.B.); Laval University and Centre Hospitalier Universitaire de Québec Research Centre, Quebec, QC, Canada (J.P.B.); Hospital del Mar, Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Autonomous University of Barcelona, Barcelona (A.D.-P.); Aarhus University Hospital, Aarhus, Denmark (B.L.L.); Instituto de Investigaciones Metabólicas, Buenos Aires (J.R.Z.); and Michigan Bone and Mineral Clinic, Detroit (H.G.B.).
出版信息
N Engl J Med. 2014 Jan 30;370(5):412-20. doi: 10.1056/NEJMoa1305224. Epub 2014 Jan 1.
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 and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups.
CONCLUSIONS
In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).
背景
骨硬化蛋白是一种成骨细胞源性的破骨细胞活性抑制剂。单克隆抗体罗莫佐单抗与骨硬化蛋白结合，增加骨形成。
方法
在一项为期 12 个月的、多中心的、国际性的、随机的、安慰剂对照的、平行分组的 8 组研究中，我们评估了罗莫佐单抗在 419 名绝经后女性（年龄 55 至 85 岁）中的疗效和安全性，这些女性的骨密度较低（腰椎、全髋或股骨颈的 T 评分低于-2.0，且三处均低于-3.5）。参与者被随机分配接受皮下注射罗莫佐单抗每月（剂量为 70mg、140mg 或 210mg）、每 3 个月（140mg 或 210mg）、皮下安慰剂或开放标签的活性对照药物-口服阿仑膦酸钠（每周 70mg）或皮下特立帕肽（每日 20μg）。主要终点是 12 个月时腰椎骨密度相对于基线的变化百分比。次要终点包括其他部位骨密度的变化百分比和骨转换标志物的变化。
结果
罗莫佐单抗的所有剂量水平均与腰椎骨密度的显著增加相关，包括 210mg 每月剂量组的增加 11.3%，而安慰剂组的减少 0.1%，阿仑膦酸钠组的增加 4.1%和特立帕肽组的增加 7.1%。罗莫佐单抗还与全髋和股骨颈骨密度的大幅增加相关，以及骨形成标志物的短暂增加和骨吸收标志物的持续减少。除了与罗莫佐单抗相关的轻微、通常是非复发性注射部位反应外，各治疗组的不良事件相似。
结论
在患有低骨量的绝经后女性中，罗莫佐单抗与骨密度增加、骨形成增加和骨吸收减少相关。（由安进公司和优时比制药公司资助；临床试验.gov 编号，NCT00896532）。
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