Denosumab withdrawal increases vertebral fracture and mortality risk compared with zoledronate.

IF 5.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

European Journal of Endocrinology Pub Date : 2025-03-03 DOI:10.1093/ejendo/lvaf013

Ko-Hsiu Lu, Shiow-Ing Wang, Shun-Fa Yang

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引用次数: 0

Abstract

Objective: Rebound vertebral fractures (VFs) after denosumab (Dmab) withdrawal have been documented, highlighting the need for further research into this phenomenon and the importance of a well-planned strategy for discontinuing Dmab.

Methods: From the TriNetX US network, we enrolled osteoporosis patients aged 50 years or older who had withdrawn from at least 2 doses of Dmab and compared them with a matched cohort who had received at least 1 dose of zoledronate (ZOL) before discontinuation. We analyzed hazard ratios (HRs) with 95% confidence intervals (CIs) and conducted Kaplan-Meier analyses, along with subgroup analyses, drug discontinuation modification, and sensitivity analyses.

Results: After matching propensity scores (n = 10 422) between the 2 cohorts (Dmab: 11 104 and ZOL: 15 976), we found that the risks of VFs (HR = 1.479, 95% CI = 1.222-1.789) and its subcategories-thoracic (1.309, 1.023-1.674), lumbar (1.865, 1.425-2.440), and collapsed fractures (1.928, 1.462-2.542)-as well as all-cause mortality (1.588, 1.475-1.710), were significantly higher in the Dmab group compared with the ZOL group. Stratified analyses showed increased VF risks in Dmab patients who were female, aged 50-64, 65 years or older, and white, regardless of fracture history compared with those using ZOL.

Conclusion: After adjusting for drug discontinuation, Dmab showed an increased risk of VFs within the first 2 years, contributing to an elevated overall mortality risk. Sensitivity analyses revealed consistent results across different regions.

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与唑来膦酸盐相比，停用Denosumab增加椎体骨折和死亡风险。

目的：Denosumab （Dmab）停药后反弹性椎体骨折（VFs）已被记录，强调了对这一现象进行进一步研究的必要性，以及Dmab停药计划良好策略的重要性。方法：从TriNetX美国网络中，我们招募了年龄在50岁或以上的骨质疏松症患者，这些患者至少停用了两个剂量的Dmab，并将他们与在停药前至少接受过一个剂量的唑来膦酸盐（ZOL）的匹配队列进行比较。我们分析了95%可信区间（CI）的风险比（HR），并进行了Kaplan-Meier分析，以及亚组分析、停药修改和敏感性分析。结果：在两个队列（Dmab: 11,104和ZOL: 15,976）之间匹配倾向评分（n = 10,422）后，我们发现Dmab组的VFs （HR = 1.479, 95% CI = 1.222-1.789）及其亚类别-胸部（1.309,1.023-1.674），腰椎（1.865,1.425-2.440）和塌陷骨折（1.928,1.462-2.542）的风险以及全因死亡率（1.588,1.475-1.710）明显高于ZOL组。分层分析显示，与使用ZOL的患者相比，Dmab患者中女性、年龄在50-64岁、65岁或以上以及白人的VF风险增加，与骨折史无关。结论：在调整停药后，Dmab显示前两年内VFs的风险增加，导致总体死亡风险升高。敏感性分析显示，不同地区的结果一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.