Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)
Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)
复制标题
DOI：
10.1007/s00198-014-2964-2
复制
发表时间：
2015-02-01
影响因子：
4
通讯作者：
Nakamura, T.
中科院分区：
文献类型：
--
作者：
Sugimoto, T.;Matsumoto, T.;Nakamura, T.
在日本骨质疏松症患者中进行的一项为期12个月的DIRECT延长期研究表明，在日本绝经后骨质疏松症患者中，denosumab治疗3年的患者骨折率低、骨转换标志物（BTM）持续降低、骨矿物质密度（BMD）持续增加、总体获益/风险状况良好。DIRECT试验表明，与安慰剂相比，在日本绝经后骨质疏松症的女性和男性中，每6个月皮下注射denosumab 60mg治疗2年可显著降低椎体骨折的发生率。本研究的目的是评估denosumab治疗长达3年的有效性和安全性。该研究包括一个为期2年的随机、双盲、安慰剂对照期和一个为期1年的开放标签扩展期，其中所有受试者均接受denosumab治疗。这些数据对应于双盲期接受denosumab治疗的受试者（长期组）3年的denosumab治疗和接受安慰剂治疗的受试者（交叉组）1年的denosumab治疗。完成双盲阶段的810名受试者进入扩展阶段，775名受试者完成了研究。所有受试者均接受denosumab治疗，每日补充钙和维生素d。在长期治疗组中，36个月累计新发或恶化椎体骨折和新发椎体骨折的发生率分别为3.8%和2.5%。在该组中，BMD继续增加，btm的减少保持不变。在交叉组中，证实了与长期组第一年相比，骨密度增加和骨密度减少的可比性。不良事件未显示长期使用地诺单抗显著增加。交叉组发生1例颌骨骨坏死。在日本骨质疏松患者中，3年的denosumab治疗显示出良好的获益/风险概况。
A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile.The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years.This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase.Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group.Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.