Abstract
SUMMARY: Utilizing the Mendelian randomization technique, this research clarifies the putative causal relationship between body mass index (BMI) andbone mineral density (BMD), and the mediating role of low-density lipoprotein (LDL). The implications of these findings present promising opportunities for enhancing our understanding of complex bone-related characteristics and disorders, offering potential directions for treatment and intervention. OBJECTIVE: The objective of this study is to examine the correlation between BMI and BMD, while exploring the intermediary role of LDL in mediating the causal impact of BMI on BMD outcomes via Mendelian randomization. METHODS: In this study, we employed genome-wide association study (GWAS) data on BMI, LDL, and BMD to conduct a comparative analysis using both univariate and multivariate Mendelian randomization. RESULTS: Our study employed a two-sample Mendelian randomization design. Considering BMI as the exposure and BMD as the outcome, our results suggest that BMI may function as a potential protective factor for BMD (β = 0.05, 95% CI 1.01 to 1.09, P = 0.01). However, when treating LDL as the exposure and BMD as the outcome, our findings indicate LDL as a risk factor for BMD (β = -0.04, 95% CI 0.92 to 0.99, P = 0.04). In our multivariate Mendelian randomization (MVMR) model, the combined influence of BMI and LDL was used as the exposure for BMD outcomes. The analysis pointed towards a substantial protective effect of LDL on BMD (β = 0.08, 95% CI 0.85 to 0.97, P = 0.006). In the analysis of mediation effects, LDL was found to mediate the relationship between BMI and BMD, and the effect was calculated at (β = 0.05, 95% CI 1.052 to 1.048, P = 0.04). CONCLUSION: Our findings suggest that BMI may be considered a protective factor for BMD, while LDL may act as a risk factor. Moreover, LDL appears to play a mediatory role in the causal influence of BMI on BMD.