Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank

IF 9.1 1区医学 Q1 GERIATRICS & GERONTOLOGY Journal of Cachexia Sarcopenia and Muscle Pub Date : 2024-10-29 DOI:10.1002/jcsm.13611

Xi Xiong, David T. W. Lui, Chengsheng Ju, Ziyi Zhou, Chao Xu, Paul Welsh, Naveed Sattar, Carlos Celis-Morales, Jill P. Pell, Ian C. K. Wong, Carlos K. H. Wong, Frederick K. Ho

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Abstract

Background

Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population.

Methods

This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37–73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk.

Results

Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality.

Conclusions

Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

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血清脂质特征与骨折和骨质疏松症的关系：英国生物库前瞻性队列研究》。

背景：先前的研究显示，普通人群的血清脂质特征与骨折和骨质疏松症风险之间的关系并不一致：以往的研究显示，普通人群的血清脂质特征与骨折和骨质疏松症风险之间的关系并不一致：这项前瞻性队列研究分析了 414 302 名英国生物库参与者（223 060 名女性和 191 242 名男性，年龄在 37-73 岁之间）的血清脂质测量数据：脂蛋白 A (载脂蛋白 A)、载脂蛋白 B (载脂蛋白 B)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL-C)、低密度脂蛋白胆固醇 (LDL-C)、甘油三酯 (TG) 和脂蛋白 A (Lp(a))。采用带惩罚性立方样条的多变量 Cox 比例危险模型来探讨每种血脂特质与骨折和骨质疏松症风险的潜在非线性关系。按年龄、性别、体重指数类别和原有心血管疾病进行了分组分析。使用 g 公式进行了中介分析，以量化骨矿物质密度（BMD）在多大程度上可能会中介血清脂质与骨折风险之间的关系：中位随访期为 13.8 年，在 383 530 名无骨折史的参与者中，有 25 918 人（6.8%）发生骨折，在 184 919 名有初级保健数据且无基线骨质疏松症的参与者中，有 7591 人（4.1%）被诊断为骨质疏松症。总胆固醇与骨折和骨质疏松症呈非线性关系，而载脂蛋白 B、总胆固醇和低密度脂蛋白胆固醇呈线性关系。载脂蛋白 A 和高密度脂蛋白胆固醇与骨折也存在非线性关系。载脂蛋白 A（骨折：HR 1.15 [95% CI 1.10，1.21]；骨质疏松症：HR 1.13 [1.02，1.25]）和高密度脂蛋白胆固醇（骨折：HR 1.27 [1.20，1.34]；骨质疏松症：HR 1.31 [1.18，1.46]）五分位数最高的人骨折和骨质疏松症的风险较高。相反，载脂蛋白 B（骨折：HR 0.85 [0.81, 0.89]；骨质疏松症：HR 0.86 [0.79, 0.94]）、LDL-C（骨折：HR 0.89 [0.85，0.93]；骨质疏松症：HR 0.91 [0.83，1.00]）和 TG（骨折：HR 0.78 [0.74，0.82]；骨质疏松症：HR 0.75 [0.68，0.82]）与较低风险相关。与女性相比，男性载脂蛋白 A（HR 比值为 1.05 [1.02, 1.09]）和高密度脂蛋白胆固醇（HR 比值为 1.06 [1.03, 1.09]）与骨折风险的关系更为明显。除总胆固醇和脂蛋白（a）外，假设存在因果关系，血清脂质与骨折之间的关联似乎部分通过 BMD（中介比例：5.30% 至 40.30%）来中介：我们的研究揭示了不同血脂指标与骨骼健康之间复杂的相互作用，其中部分可能通过 BMD 起中介作用。常规血脂特征评估，包括高密度脂蛋白胆固醇和载脂蛋白 A 以及其他血脂特征，可纳入骨折风险分层策略中。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.