Investigating the association between osteoporosis and acute myocardial infarction using Mendelian randomisation and bioinformatics.

Background

Osteoporosis and acute myocardial infarction (AMI) are major health challenges in the aging population. Osteoporosis increases bone fragility, while AMI, often due to atherosclerosis, causes myocardial ischemia and inflammation. Their co-morbidity and shared mechanisms remain unclear.

Objective

To explore the causal relationship and shared molecular mechanisms between osteoporosis and AMI.

Methods

GWAS data from the Risteys FinnGen R9 database (osteoporosis: 621 cases, 122,861 controls) and the IEU Open GWAS program (AMI: 20,917 cases, 461,823 controls) were analyzed using Mendelian Randomization (IVW, MR-Egger, weighted median). Gene expression datasets (GSE56815, GSE48060) were used to identify differentially expressed genes (DEGs). Functional enrichment, immune infiltration (MCPcounter), and weighted gene co-expression network analysis (WGCNA) were performed, and overlapping hub genes were identified.

Results

MR analysis demonstrated a significant causal association between osteoporosis and AMI. Transcriptomic analysis revealed 2434 DEGs in osteoporosis and 2827 in AMI. Enrichment highlighted pathways including immune regulation, MAPK signaling, and cancer-related pathways. Immune infiltration showed altered monocytes and dendritic cells in osteoporosis, and cytotoxic lymphocytes and neutrophils in AMI. WGCNA identified 6 modules in osteoporosis and 11 in AMI, with 1423 common hub genes.

Conclusion

Osteoporosis and AMI share genetic and molecular mechanisms, especially involving inflammation and calcium signaling. These findings provide new insights into their co-morbidity and suggest that targeting shared therapeutic pathways may support integrated strategies for improving bone and cardiovascular health.