Effect of Denosumab on Bone Mineral Density and Biochemical Markers of Bone Turnover: Six-Year Results of a Phase 2 Clinical Trial
Effect of Denosumab on Bone Mineral Density and Biochemical Markers of Bone Turnover: Six-Year Results of a Phase 2 Clinical Trial
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DOI：
10.1210/jc.2010-1805
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发表时间：
2011-02-01
影响因子：
5.8
通讯作者：
McClung, Michael R.
中科院分区：
文献类型：
--
作者：
Miller, Paul D.;Wagman, Rachel B.;McClung, Michael R.
内容：这是一项研究扩展，以评估的有效性和安全性的长期治疗与denosumab在绝经后妇女低bone mass.Objective：我们的目的是描述骨矿物质密度（BMD）和骨转换标志物的变化，以及安全性与6年denosumab treatment.Design：我们进行了一项正在进行的4年，开放标签，单臂，剂量范围2期试验的扩展研究。本文报告了一项为期2年的中期分析，代表了长达6年的连续denosumab治疗。S. centers.Patients:在完成母研究的262名受试者中，200名入组了研究扩展，178名（89%）完成了前2年的干预：所有受试者每6个月接受Denosumab 60 mg sc。主要结果测量：我们评估了腰椎、全髋关节、股骨颈和三分之一桡骨的BMD;骨转换的生化标志物;以及安全性，报告为不良事件。在6年的时间内，地舒单抗连续治疗导致低骨量绝经后妇女的BMD逐渐增加。在连续治疗过程中，骨吸收持续减少。与既往治疗和停药期无关，通过BMD和骨转换标志物测量，受试者显示出对地舒单抗治疗的反应性。denosumab的安全性并没有随着时间的推移而改变。结论：在这项研究中，denosumab是耐受性良好，有效的，通过6年的连续治疗绝经后妇女低骨量。（临床内分泌代谢杂志96：394-402，2011）
Context: This is a study extension to evaluate the efficacy and safety of long-term treatment with denosumab in postmenopausal women with low bone mass.Objective: Our objective was to describe changes in bone mineral density (BMD) and bone turnover markers as well as safety with 6 yr of denosumab treatment.Design: We conducted an ongoing 4-yr, open-label, single-arm, extension study of a dose-ranging phase 2 trial. This paper reports a 2-yr interim analysis representing up to 6 yr of continuous denosumab treatment.Setting: This multicenter study was conducted at 23 U. S. centers.Patients: Of the 262 subjects who completed the parent study, 200 enrolled in the study extension and 178 (89%) completed the first 2 yr.Intervention: All subjects received denosumab 60 mg sc every 6 months.Main Outcome Measures: We evaluated BMD at the lumbar spine, total hip, femoral neck, and one third radius; biochemical markers of bone turnover; and safety, reported as adverse events.Results: Over a period of 6 yr, continuous treatment with denosumab resulted in progressive gains in BMD in postmenopausal women with low bone mass. Reduction in bone resorption was sustained over the course of continuous treatment. Independent of past treatment and discontinuation period, subjects demonstrated responsiveness to denosumab therapy as measured by BMD and bone turnover markers. The safety profile of denosumab did not change over time.Conclusions: In this study, denosumab was well tolerated and effective through 6 yr of continuous treatment in postmenopausal women with low bone mass. (J Clin Endocrinol Metab 96: 394-402, 2011)