Zoledronate Sequential Therapy After Denosumab Discontinuation to Prevent Bone Mineral Density Reduction: A Randomized Clinical Trial.

IF 10.5 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL JAMA Network Open Pub Date : 2024-11-04 DOI:10.1001/jamanetworkopen.2024.43899
Chia-Che Lee, Chen-Yu Wang, Hung-Kuan Yen, Chih-Chien Hung, Cheng-Yo Lai, Ming-Hsiao Hu, Ting-Ming Wang, Chung-Yi Li, Shau-Huai Fu
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Abstract

Importance: Discontinuation of denosumab without transitioning to another antiresorptive agent results in rapid bone loss and an increased risk of fracture. Previous randomized studies reported inconsistent results regarding the efficacy of zoledronate as sequential therapy.

Objective: To investigate the use of sequential therapy with zoledronate to prevent bone loss and decreased bone mineral density (BMD) after denosumab discontinuation in the first year.

Design, setting, and participants: The Denosumab Sequential Therapy prospective, open-label, parallel-group randomized clinical trial was conducted at a referral center and 2 affiliated hospitals in Taiwan. Recruitment was conducted from April 1, 2019, to May 31, 2021, and a 2-year follow-up was planned. The trial included postmenopausal women and men aged 50 years or older who received regular denosumab treatment for at least 2 years and did not have previous exposure to other antiosteoporosis medication or meet other exclusion criteria.

Intervention: Participants were assigned via stratified randomization to 1 of 2 groups: group A received continuous denosumab treatment (60 mg twice yearly) as the positive control, whereas group ZOL received 1 dose of zoledronate (5 mg) in the first year.

Main outcomes and measures: The coprimary outcomes were BMD percentage changes in the lumbar spine (LS-BMD), total hip (TH-BMD), and femoral neck (FN-BMD), respectively. An intention-to-treat analysis was performed.

Results: This study included 101 patients (95 women [94.1%]; median age, 72.0 [IQR, 67.0-76.0] years). There were 25 patients in group A (23 women [92.0%]; median age, 74.0 [IQR, 70.0 to 78.0] years) and 76 in group ZOL (72 women [94.7%]; median age, 71.0 [IQR, 65.7 to 76.0] years). In the first year, group ZOL had a significant median decrease in LS-BMD (-0.68% [IQR, -3.22% to 2.75%]) compared with group A (1.30% [IQR, -0.68% to 5.24%]) (P = .03). No significant differences between groups A and ZOL were observed for TH-BMD (median, 1.12% [IQR, -0.06% to 2.25%] vs 0% [-1.47% to 2.15%]) (P = .24) and FN-BMD (median, 0.17% [IQR, -2.29% to 2.90%] vs 0.18% [-2.73% to 3.88%]) (P = .71). We observed a significant difference in the median LS-BMD percentage change for the ZOL subgroup with 3 or more years of denosumab treatment before enrollment (-3.20% [IQR, -7.89% to 0.68%]) compared with group A (1.30% [IQR, -0.68% to 5.24%]) (P = .003).

Conclusions and relevance: In this randomized trial of sequential therapy after denosumab discontinuation, bone loss was observed in LS-BMD in the first year among patients receiving zoledronate. A longer duration of denosumab treatment was associated with a further decrease in LS-BMD after zoledronate sequential therapy. Further randomized clinical trials and large-scale studies that investigate the strategies of sequential therapy after long-term denosumab treatment are needed.

Trial registration: ClinicalTrials.gov Identifier: NCT03868033.

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停用地诺单抗后使用唑来膦酸钠序贯疗法预防骨矿物质密度降低:随机临床试验
重要性:停用地诺单抗而不过渡到另一种抗骨吸收药物会导致骨量快速流失,增加骨折风险。之前的随机研究报告显示,唑来膦酸钠作为序贯疗法的疗效并不一致:目的:研究使用唑来膦酸钠进行序贯治疗,以防止在停用地诺单抗第一年后出现骨丢失和骨矿物质密度(BMD)降低:地诺单抗序贯疗法前瞻性、开放标签、平行组随机临床试验在台湾的一家转诊中心和两家附属医院进行。招募时间为2019年4月1日至2021年5月31日,计划随访2年。试验对象包括50岁或以上的绝经后女性和男性,他们接受正规的地诺单抗治疗至少2年,既往未使用过其他抗骨质疏松症药物,也不符合其他排除标准:干预措施:通过分层随机法将参与者分配到两组中的一组:A组接受持续的地诺单抗治疗(60毫克,每年两次)作为阳性对照,而ZOL组在第一年接受1次唑来膦酸钠(5毫克)治疗:主要结果和测量指标:主要结果是腰椎(LS-BMD)、全髋(TH-BMD)和股骨颈(FN-BMD)的BMD百分比变化。研究进行了意向治疗分析:本研究共纳入 101 名患者(95 名女性 [94.1%];中位年龄 72.0 [IQR, 67.0-76.0] 岁)。A 组有 25 名患者(23 名女性 [92.0%];中位年龄 74.0 [IQR,70.0-78.0]岁),ZOL 组有 76 名患者(72 名女性 [94.7%];中位年龄 71.0 [IQR,65.7-76.0]岁)。与 A 组(1.30% [IQR, -0.68% to 5.24%])相比,ZOL 组在第一年的 LS-BMD 中位数显著下降(-0.68% [IQR, -3.22% to 2.75%])(P = .03)。A组和ZOL组在TH-BMD(中位数,1.12% [IQR, -0.06% to 2.25%] vs 0% [-1.47% to 2.15%])(P = .24)和FN-BMD(中位数,0.17% [IQR, -2.29% to 2.90%] vs 0.18% [-2.73% to 3.88%])(P = .71)方面无明显差异。我们观察到,与 A 组(1.30% [IQR, -0.68% to 5.24%])相比,入组前接受过 3 年或 3 年以上地诺单抗治疗的 ZOL 亚组的 LS-BMD 百分比变化中位数(-3.20% [IQR, -7.89% to 0.68%])有显著差异(P = .003):在这项关于停用地诺单抗后序贯治疗的随机试验中,观察到接受唑来膦酸钠治疗的患者第一年的 LS-BMD 骨量有所下降。在接受唑来膦酸盐序贯疗法后,地诺单抗治疗时间的延长与LS-BMD的进一步下降有关。需要进一步开展随机临床试验和大规模研究,探讨长期使用地诺单抗治疗后的序贯治疗策略:试验注册:ClinicalTrials.gov Identifier:试验注册:ClinicalTrials.gov Identifier:NCT03868033。
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JAMA Network Open
JAMA Network Open Medicine-General Medicine
CiteScore
16.00
自引率
2.90%
发文量
2126
审稿时长
16 weeks
期刊介绍: JAMA Network Open, a member of the esteemed JAMA Network, stands as an international, peer-reviewed, open-access general medical journal.The publication is dedicated to disseminating research across various health disciplines and countries, encompassing clinical care, innovation in health care, health policy, and global health. JAMA Network Open caters to clinicians, investigators, and policymakers, providing a platform for valuable insights and advancements in the medical field. As part of the JAMA Network, a consortium of peer-reviewed general medical and specialty publications, JAMA Network Open contributes to the collective knowledge and understanding within the medical community.
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