Associations of Dietary and Circulating Choline and Glycine With Bone Mineral Density: UK Biobank Analyses With Mendelian Randomization.

Abstract

Osteoporosis, characterized by reduced bone mass and compromised bone microarchitecture, significantly impacts public health, particularly among the elderly population. Although choline and its related metabolites are believed to influence bone health, their exact role and the effects of these metabolites on bone mineral density (BMD) remain unclear. We analyzed data from 18,769 UK Biobank (UKB) participants, excluding those with missing data or specific health conditions. All observational associations were assessed cross-sectionally at baseline. Choline intake was assessed using a self-administered 24-h dietary assessment, while circulating choline and related metabolites were quantified by nuclear magnetic resonance spectroscopy. BMD was measured using ultrasound densitometry. Linear regression models were used to assess the associations, adjusting for various covariates. Overall, circulating choline levels demonstrated a borderline significant association with BMD ( β = -0.0056, p = 0.052), and glycine levels showed a significantly negative association ( β = -0.0486, p = 0.004). Subgroup analyses revealed that the association between circulating choline and BMD varied by gender, menopausal status, and renal function. Notably, higher choline levels were related to lower BMD in men ( β = -0.0097, p = 0.032) and those with impaired kidney function ( β = -0.01, p = 0.034). While dietary choline intake did not show an overall significant relationship with BMD ( β = -0.0128, p = 0.218), a negative association was observed in individuals with renal impairment ( β = -0.0385, p = 0.027). Furthermore, Mendelian randomization analyses suggested a potential causal association between circulating choline levels and BMD in men ( β = -0.079, 95% CI: -0.117 to -0.040, p < 0.001) and between glycine levels and BMD in women ( β = -0.022, 95% CI: -0.037 to -0.007, p = 0.005). Choline and glycine metabolism may play a role in bone metabolism, with choline showing particular effects in men and individuals with impaired renal function. Further research is necessary to better understand the underlying mechanisms and implications of these associations for osteoporosis risk in different populations.