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

BACKGROUND

Studies have examined the connection between blood metabolites, osteoporosis (OP), and hypertension; however, there is not enough data to pinpoint their precise cause.

METHODS

OP and associated traits served as outcomes, with hypertension serving as the 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. Finally, to find putative mediating metabolites, a two-step Mendelian randomization (MR) analysis was carried out.

RESULTS

IVW analysis revealed a substantial negative connection between hypertension and lumbar spine bone mineral density (odds ratio [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.