Abstract
BACKGROUND: The impact of lipid metabolism on bone metabolism remains controversial, and the extent to which human traits mediate the effects of lipid metabolism on bone metabolism remains unclear. OBJECTIVE: This study utilized mendelian randomization to investigate the effects of blood lipids on bone mineral density (BMD) at various skeletal sites and examined the mediating role of human traits in this process. METHODS: We leveraged genetic data from large-scale genome-wide association studies on blood lipids (n=1,320,016), forearm bone mineral density (FA-BMD) (n=10,805), lumbar spine bone mineral density (LS-BMD) (n=44,731), and femoral neck bone mineral density (FN-BMD) (n=49,988) to infer causal relationships between lipid and bone metabolism. The coefficient product method was employed to calculate the indirect effects of human traits and the proportion of mediating effects. RESULTS: The results showed that a 1 standard deviation(SD) increase in HDL-C, LDL-C and TC was associated with a decrease in LS-BMD of 0.039 g/cm(2), 0.045 g/cm(2) and 0.054 g/cm(2), respectively. The proportion of mediating effects of systolic blood pressure (SBP) on HDL-C to LS-BMD was 3.17%, but suppression effects occurred in the causal relationship of LDL-C and TC to LS-BMD. Additionally, the proportion of mediating effects of hand grip strength (HGS) on the TC to LS-BMD pathway were 6.90% and 4.60% for the left and right hands, respectively. CONCLUSION: In conclusion, a negative causal relationship was established between lipid metabolism and bone metabolism. Our results indicated that SBP and HGS served as mediators for the effects of lipid metabolism on bone metabolism.