BackgroundPrevious studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population.MethodsThis 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.ResultsOver 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.ConclusionsOur 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.

中文翻译：

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血脂性状与骨折和骨质疏松症的关联：来自英国生物样本库的前瞻性队列研究


背景先前的研究揭示了血脂特征与普通人群骨折和骨质疏松症风险之间的不一致关联。方法这项前瞻性队列研究分析了来自 414 302 名英国生物样本库参与者（223 060 名女性和 191 242 名男性，年龄在 37-73 岁之间）的数据，血清脂质测量：载脂蛋白 A （Apo A）、载脂蛋白 B （Apo 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））。使用具有惩罚三次样条的多变量 Cox 比例风险模型来探索每种脂质性状与骨折和骨质疏松症风险的潜在非线性关联。按年龄、性别、BMI 类别和预先存在的心血管疾病进行亚组分析。使用 g 公式进行中介分析，以量化骨密度 （BMD） 在多大程度上介导血脂与骨折风险之间的关联。结果在 13.8 年的中位随访期内，383 530 名既往无骨折史的参与者中有 25 918 名 （6.8%） 有骨折病例，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 名 （4.1%） 被诊断为骨质疏松症。TG 与骨折和骨质疏松症呈非线性关联，而 Apo B 、 TC 和 LDL-C 呈线性关联。Apo A 和 HDL-C 与骨折也存在非线性关联。Apo 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 HDL-C（骨折：HR 1.27 [1.20,1.34];骨质疏松症：HR 1.31 [1.18,1.46]）最高的五分位数个体与骨折和骨质疏松症的风险较高相关。 相反，Apo 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]）与较低的风险相关。与女性相比，男性的 Apo A （HR [RHR] 比值 [1.02， 1.09]）和 HDL-C （RHR 1.06 [1.03， 1.09]）与骨折风险的相关性更为明显。假设存在因果关系，除 TG 和 Lp（a） 外，血脂与骨折之间的关联似乎部分通过 BMD 介导（中介比例：5.30% 至 40.30%）。结论我们的研究揭示了不同脂质标志物与骨骼健康之间的复杂相互作用，可能部分通过 BMD 介导。常规血脂评估，包括 HDL-C 和 Apo A 以及其他血脂性状，可以整合到骨折风险分层策略中。