Causal effects among hypertension, osteoporosis, and metabolites: A Mendelian randomization study

BACKGROUND: Studies have looked at the connection between blood metabolites, osteoporosis (OP), and hypertension; however, there is not enough data to pinpoint their precise cause. METHOD: OP and associated traits served as outcomes, with hypertension serving as exposure variable. The main methodology was the random-effects inverse variance weighted (IVW) technique. Horizontal pleiotropy and heterogeneity of outcomes were assessed by sensitivity testing. Lastly, to find putative mediating metabolites, a two-step MR analysis was carried out. RESULTS: IVW analysis revealed a substantial negative connection of hypertension with lumbar spine bone mineral density (OR=0.961, 95%CI: 0.927-0.997, P<0.05) and heel bone mineral density (OR=0.982, 95%CI: 0.971-0.992, P<0.001), as well as a strong positive correlation with OP (OR=1.165, 95%CI: 1.067-1.273, P<0.001). Sensitivity analysis validated the robustness of the results. The blood metabolites (R)-3-hydroxybutyrylcarnitine, 1-(1-enyl-palmitoyl)-GPE (p-16:0), hydroxyasparagine, Adenosine 5'-diphosphate (ADP) to 5-oxoproline ratio, Sphinganine-1-phosphate levels and Sphingosine 1-phosphate levels showed preliminary suggestive mediating effects on the association between hypertension and decreased bone mineral density in statistics. CONCLUSION: Our study revealed a positive correlation between hypertension and OP, and suggested that blood metabolites may play a mediating role in it. These findings provide clues for a deeper understanding of the potential mechanisms between hypertension and bone health, and lay a scientific foundation for exploring targeted intervention strategies in the future.