Statins and longitudinal changes in vertebral bone mineral density in an emulated target trial: the multi-ethnic study of atherosclerosis

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-09-22 DOI:10.1016/j.bone.2025.117659

Elena Ghotbi , Quincy A. Hathaway , Roham Hadidchi , Michael P. Bancks , David A. Bluemke , Mei Wan , R. Graham Barr , Wendy S. Post , Matthew Budoff , Benjamin M. Smith , João A.C. Lima , Shadpour Demehri

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Abstract

Background

Existing reports on the protective effects of statins on bone health have been conflicting, which may have been related to the diverse selectivity of studied populations. We aimed to evaluate the association between statin initiation and longitudinal changes in vertebral bone mineral density (BMD) over six years.

Methods

This emulated target trial used data from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants with a baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5 % at MESA Exam 4 or 5 and no history of prevalent statin use were included. Statin initiators were propensity score matched to non-initiators.

The primary outcome was longitudinal change in CT-derived multilevel vertebral (T1–T10) BMD, assessed using linear mixed-effects models. Prespecified interaction terms and subsequent subgroup analyses were performed by age, sex, race/ethnicity, body mass index, high-sensitivity C-reactive protein (hs-CRP), physical activity, diabetes status, smoking, and alcohol use. We used an array approach to evaluate the magnitude and prevalence of residual confounding necessary to fully explain our main observation.

Results

A total of 384 participants (173 statin initiators; 211 non-initiators) were included in the per-protocol analysis. Statin initiation was associated with a slower decline in vertebral BMD (estimated difference, β = 1.00 g/cm³/year; 95 % CI, 0.65–1.35; p < 0.001), corresponding to a 0.47 % slower annual decline. An unmeasured confounder associated with a 1 % annual relative difference in BMD change would need to be at least three times as prevalent among statin initiators compared with non-initiators to nullify the observed effect size. Subgroup analyses suggested stronger protective associations among participants with impaired fasting glucose or diabetes, lower hs-CRP, and higher physical activity.

Conclusions

In this emulated target trial, statin initiation was associated with beneficial bone health effects.

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在一项模拟靶试验中，他汀类药物和椎体骨密度的纵向变化：动脉粥样硬化的多种族研究

关于他汀类药物对骨骼健康的保护作用的现有报告存在矛盾，这可能与研究人群的不同选择性有关。我们的目的是评估他汀类药物起始治疗与6年内椎体骨密度（BMD）纵向变化之间的关系。方法本模拟靶试验采用多民族动脉粥样硬化研究（MESA）的数据。在MESA检查4或5时，基线10年动脉粥样硬化性心血管疾病（ASCVD）风险≥7.5%且无他汀类药物流行史的参与者被纳入研究。他汀类药物启动者倾向评分与非启动者相匹配。主要终点是ct衍生的多节段椎体（T1-T10）骨密度的纵向变化，使用线性混合效应模型进行评估。预先指定的相互作用项和随后的亚组分析按年龄、性别、种族/民族、体重指数、高敏c反应蛋白（hs-CRP）、身体活动、糖尿病状况、吸烟和饮酒进行。我们使用阵列方法来评估充分解释我们的主要观察结果所必需的残留混淆的大小和流行程度。结果384名受试者（173名他汀类药物启动者，211名非他汀类药物启动者）被纳入方案分析。开始服用他汀类药物与椎体骨密度下降较慢相关（估计差异，β = 1.00 g/cm3/年；95% CI, 0.65-1.35; p < 0.001），相当于年下降速度减慢0.47%。未测量的混杂因素与每年1%的BMD变化相对差异相关，在他汀类药物启动者中与非启动者相比，至少需要三倍的流行率才能使观察到的效应大小无效。亚组分析表明，空腹血糖受损或糖尿病患者、hs-CRP较低和体力活动较多的参与者之间存在更强的保护关联。结论在这个模拟靶试验中，他汀类药物起始与有益的骨健康效应相关。

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

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.