Causal effects among hypertension, osteoporosis, and metabolites: A Mendelian randomization study
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Authors: Yiguo Chen, Wei Wang, Xidong Xu, Xiaohua Huang, Bing Wei, Hongliang Jin, Qiyuan Pan, Yang Yang, Zhangyu Wang, Chao Feng, Li Chen, Zhijun Zhao, Yao Su
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7164900616
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