Background Cardiovascular disease (CVD) may have some association with osteoporosis (OP). This Mendelian randomization (MR) investigation aimed to explore the potential causal linkage between CVD and OP.

Methods Utilizing genome-wide association study data from individuals of European descent, we pinpointed Single Nucleotide Polymorphisms (SNPs) relevant to CVD, including those for coronary heart disease (CHD) with 64,762 cases and 22,233 controls, heart failure (HF) comprising 47,309 cases against 930,014 controls, and stroke with a case-control tally of 3,611 to 18,084, to serve as the instrumental variables. Later, we searched for total body bone mineral density (BMD) statistics which were used as phenotypes for OP(sample size = 56,284). In this paper, the traditional inverse variance weighting (IVW) method, the weighted median estimation method, and the MR-Egger method are used to estimate different results. The MR-Egger intercept test, outlier (Mr-PRESSO) test and Cochran-Q statistic are used to detect potential directional pleiotropy and heterogeneity, while we also draw the scatter plot, funnel plot and forest plot. Additionally, a reverse-direction MR analysis was performed to explore the potential for reverse causation.

Results The IVW analysis showed that CHD could significantly impact total body BMD levels, and every higher standard deviation in the risk of CHD decreased the average total body BMD by 0.0459 units in the IVW analysis(Beta = -0.0459; 95%CI = -0.0815 –-0.0104, P = 0.0113). Reverse MR analysis showed no significant correlation of the change of total body BMD on the prevalence effect of CHD. No particular relationship exists between HF and total body BMD. There was no significant effect between the changes in total body BMD induced by stroke. Reverse MR analysis revealed no significant correlation between alterations in total body BMD on stroke.

Conclusion Our analysis points to a substantial causative link between CHD and the vulnerability to OP, potentially paving the way for innovative approaches in treating and preventing OP.

The authors have declared no competing interest.

This research was funded by the project "Therapeutic Strategy and Instrument Development of the Bone Defect Caused by War Trauma," grant number CX2019LC121.

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