We conducted this cross-sectional study to investigate the independent associations between lipid metabolites and osteoporotic fractures among participants aged 40–69 years from the UK Biobank. Serum lipid, lipoprotein levels and nuclear magnetic resonance (NMR) based metabolic biomarkers were measured at the baseline. We conducted multivariable logistic analyses to investigate potential independent associations between concentrations of lipid metabolites and osteoporotic fractures in both men and women. The odds ratios (ORs) for lipid metabolites were calculated based on their lowest tertile. Over a median follow-up period of 15 years, a total of 978 men and 4515 women were diagnosed with osteoporosis, whereas 138 men and 327 women encountered incident fractures. Statistically significant disparities were identified in NMR-based metabolic biomarkers among men and women with incident fractures compared to those without. Out of the 144 distinct lipid metabolites known, 35 exhibited significant associations with incident fractures in patients diagnosed with osteoporosis. Following the adjustment for confounding factors, degree of unsaturation (p = 0.0066) and docosahexaenoic acids (p = 0.0011) in male patients increased the risk of incident fractures. And high level of different metabolites of HDL (p = 0.0153), 3-Hydroxybutyrate (p = 0.0012) and Sphingomyelins (p = 0.0036) decreased the risk of incident fractures in female patients. This outcome indicates that these identified lipid metabolites may potentially have unique roles in independently contributing to the occurrence of osteoporotic fractures.
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