Cai Jie, Huang Huan, Hu Huaying, Qi Lu, Zhou Tao
Department of Epidemiology, School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Bone. 2025 Jun;195:117460. doi: 10.1016/j.bone.2025.117460. Epub 2025 Mar 19.
The study aimed to explore associations of metabolomic data based on nuclear magnetic resonance (NMR) with the risk of fractures and bone mineral density (BMD).
We included 69,963 participants without fractures at baseline in the UK Biobank. Cox proportional hazard models were used to estimate the associations of metabolomic biomarkers measured by NMR technology with the risk of all fractures and hip fracture. We used principal component analysis (PCA) to obtain uncorrelated principal components (PC), which were further used to estimate the associations of each PC with BMD, all fractures, and hip fracture separately.
During a median follow-up of 12.6 years, 3840 incidents of all fractures and 666 incidents of hip fracture were documented. Ninety-four of the 143 metabolomic biomarkers were significantly associated with incident all fractures, and 81 were significantly associated with incident hip fracture. The very low-density lipoprotein (VLDL) subclasses in different lipid constituents were associated with increased BMD at multiple sites, whereas high-density lipoprotein (HDL) subclasses were associated with decreased BMD. Higher concentrations of small (HR per SD increment: 0.92; 95 % CI: 0.88-0.97), medium (HR per SD increment: 0.91; 95 % CI: 0.88-0.94), and large (HR per SD increment: 0.93; 95 % CI: 0.90-0.96) low-density lipoprotein (LDL) particles were associated with a lower risk of all fractures. Similarly, higher VLDL subclasses (excluding very small VLDL particles) were associated with a lower risk of all fractures. Besides, higher levels of lipid constituents (including total lipids, cholesteryl esters, cholesterol, and free cholesterol) of very large and large HDL were associated with an increased risk of all fractures. PC1 (mainly contributed by lipid subclasses of LDL and VLDL), which explained the most variance of individual biomarkers, showed a negative association with the risk of all fractures (P = 7.80E-08). Similar associations were observed for hip fracture.
Higher levels of large and very large HDL were associated with an increased risk of fractures, whereas higher lipid subclasses of LDL and VLDL were associated with a lower risk of fracture. Higher levels of VLDL subclasses in different lipid constituents were associated with increased BMD at multiple sites, while higher level of HDL was associated with decreased BMD.
本研究旨在探讨基于核磁共振（NMR）的代谢组学数据与骨折风险及骨密度（BMD）之间的关联。
我们纳入了英国生物银行中69963名基线时无骨折的参与者。采用Cox比例风险模型来估计通过NMR技术测量的代谢组学生物标志物与所有骨折和髋部骨折风险之间的关联。我们使用主成分分析（PCA）来获得不相关的主成分（PC），并进一步分别用于估计每个PC与BMD、所有骨折和髋部骨折之间的关联。
在中位随访12.6年期间，记录了3840例所有骨折事件和666例髋部骨折事件。143种代谢组学生物标志物中的94种与所有骨折事件显著相关，81种与髋部骨折事件显著相关。不同脂质成分中的极低密度脂蛋白（VLDL）亚类与多个部位的骨密度增加相关，而高密度脂蛋白（HDL）亚类与骨密度降低相关。较小（每标准差增量的风险比：0.92；95%置信区间：0.88 - 0.97）、中等（每标准差增量的风险比：0.91；95%置信区间：0.88 - 0.94）和较大（每标准差增量的风险比：0.93；95%置信区间：0.90 - 0.96）的低密度脂蛋白（LDL）颗粒水平较高与所有骨折风险较低相关。同样，较高的VLDL亚类（不包括非常小的VLDL颗粒）与所有骨折风险较低相关。此外，非常大的和大的HDL的较高脂质成分水平（包括总脂质、胆固醇酯、胆固醇和游离胆固醇）与所有骨折风险增加相关。解释个体生物标志物最大变异的PC1（主要由LDL和VLDL的脂质亚类贡献）与所有骨折风险呈负相关（P = 7.80E - 08）。髋部骨折也观察到类似的关联。
较大和非常大的HDL水平较高与骨折风险增加相关，而LDL和VLDL的较高脂质亚类与骨折风险较低相关。不同脂质成分中较高的VLDL亚类水平与多个部位的骨密度增加相关，而较高的HDL水平与骨密度降低相关。
