Association of frailty with incident fractures and the mediating effect of inflammatory biomarkers: a prospective cohort study from the UK Biobank

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-09-28 DOI:10.1016/j.bone.2025.117662

Yi Zhang , Kai Zhang , Weizheng Kong , Xiaolin Hu , Lirong Chai , Weijing Wang , Dongfeng Zhang , Junning Fan

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引用次数: 0

Abstract

Background

Limited evidence exists regarding the association of frailty with fractures of different types and the potential mediating factors. This study investigated the prospective associations of frailty status with incident fracture risk and potential mediating role of inflammatory biomarkers.

Methods

This prospective cohort study utilized the UK Biobank data (median follow-up: 13.6 years). Frailty status was assessed using the frailty index (FI) and Fried's phenotype (FP). The outcomes of interest were any, vertebral, hip, and non-hip non-vertebral (NHNV) fractures. Cox regression models were employed to estimate association between frailty and fracture outcomes. Subgroup analyses by age, sex, and body mass index were conducted. Additionally, mediation analyses were performed to explore whether and quantify the extent to which inflammation may mediate the frailty-fracture association.

Results

Among 418,700 participants aged 38–72 years, frailty significantly increased risk of incident fracture, taking the frailty index as an example, with hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.53 (1.45–1.60) for any fractures, 2.33 (2.04–2.66) for vertebral fractures, 1.74 (1.55–1.95) for hip fractures, and 1.43 (1.35–1.52) for NHNV fractures. The FI-any fracture association was stronger in participants aged ≥60 years compared to younger participants (P _interaction = 0.0414); FP exhibited more pronounced associations with any fractures in men than women (P _interaction = 0.0001). Moreover, three inflammatory biomarkers - C-reactive protein, neutrophils, and platelets - significantly mediated 0.86–2.20 % of the frailty-fracture relationships.

Conclusion

Frailty was independently linked to increased risks of incident fracture, partially mediated through inflammatory biomarkers. These findings underscore the clinical importance of frailty screening in fracture prevention settings.

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虚弱与意外骨折的关联以及炎症生物标志物的中介作用：来自英国生物银行的一项前瞻性队列研究。

背景：关于不同类型骨折与虚弱的关系及其潜在的中介因素的证据有限。本研究调查了虚弱状态与意外骨折风险的潜在关联以及炎症生物标志物的潜在介导作用。方法：这项前瞻性队列研究利用了英国生物银行的数据（中位随访：13.6 年）。利用脆弱指数（FI）和弗里德表型（FP）评估脆弱状态。研究的结果包括任何椎体、髋关节和非髋关节非椎体骨折（NHNV）。采用Cox回归模型估计虚弱和骨折结局之间的关系。按年龄、性别和身体质量指数进行亚组分析。此外，还进行了中介分析，以探讨炎症是否介导脆弱-骨折关联并量化其程度。结果：在418,700名年龄在38-72 岁的参与者中，虚弱显著增加了发生骨折的风险，以虚弱指数为例，任何骨折的危险比（hr）和95 %置信区间（CIs）为1.53(1.45-1.60)，椎体骨折为2.33(2.04-2.66)，髋部骨折为1.74 (1.55-1.95)，NHNV骨折为1.43（1.35-1.52）。≥60 岁的参与者与年轻参与者相比，FI-any骨折的相关性更强（Pinteraction = 0.0414）；FP与男性骨折的相关性比女性更明显（p交互作用 = 0.0001）。此外，三种炎症生物标志物- c反应蛋白，中性粒细胞和血小板-显著介导0.86-2.20 %的脆弱-骨折关系。结论：虚弱与骨折风险增加独立相关，部分通过炎症生物标志物介导。这些发现强调了虚弱筛查在预防骨折方面的临床重要性。

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.