Bone mineral density and Sex hormone binding globulin as potential mediators of the causal effect of urolithiasis on osteoporosis risk: A mendelian randomization

Jiawei Guo Xinyu Chen ^* Yongqi Dou Xinping Yi Yongjiang Xiong Tao Zhao ^*

• Yongchuan Hospital of Chongqing Medical University, Chongqing, China

Objective: Osteoporosis (OP) and urolithiasis (UL) are two metabolic diseases that are prevalent globally. Previous observational studies have found a relationship between these two diseases that increases the risk of each other, but whether there is a direct causal link is still unclear. Currently, research on the mechanisms of these two diseases mainly focuses on external factors such as diet and environment. Thus, this study used two-sample mendelian randomization (TS-MR) in conjunction with mediation analysis to explore the causal relationship between OP and UL and their potential mechanisms. Mediators included total body bone mineral density (T-BMD), sex hormone binding globulin (SHBG), serum 25-hydroxyvitamin D (serum 25(OH)D) levels, and calcium supplements.We acquired UL-related and BMD-related single nucleotide polymorphisms (SNPs) from the MRC IEU Open Genome-Wide Association Study (GWAS) database. The primary SNPs data of osteoporosis were from the FinnGen database. To clarify the mediators involved in the link between OP and UL, we performed a MR investigation. The primary approach to analysis was inverse variance weighting (IVW). In addition, we also used another osteoporosis data from UK biobank (UKB) to further verify the mediating role.Results: We discovered that there was a 14% increase in the incidence of OP in UL patients using the IVW approach.