Association of nuclear magnetic resonance-based metabolomics with bone health in the UK Biobank

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.