The Association between the Presence of Kidney Stones and the Risk of Developing Osteoporosis: A NHANES-based Cross-sectional Study and Mendelian Randomization Analysis

Abstract Background Kidney stone disease is thought to be a risk factor for osteoporosis, but the causality between the conditions remains unknown.. Thus, we implemented a NHANES-based cross-sectional study and mendelian randomization to investigate whether the presence of kidney stones increases the risk of developing osteoporosis. Methods First, we performed an observational study on the basis of data from the National Health and Nutrition Examination Survey (NHANES; 2007–2020). Kidney stone patients were identified on the basis of their affirmative response to the question "Have you ever experienced kidney stones?" (KIQ026). Participants whose T score at the femoral neck was <-2.5 were defined as osteoporosis patients. Multivariable-adjusted logistic regression was used to assess the correlation between the presence of kidney stones and the risk of developing osteoporosis. Second, Mendelian randomization (MR) was applied to further investigate the causal relationship between the presence of kidney stones and the risk of developing osteoporosis. Genetic instruments were obtained from large genome-wide association studies (GWASs) from the UK Biobank and FinnGen Biobank. Inverse-variance weighting (IVW) was the primary analytical method used. Results After adjustment for demographic and other covariates, a significant association between the presence of kidney stones and the risk of developing osteoporosis was detected (OR 1.778, CI: 1.345–2.351, P < 0.001). The MR results further revealed that genetically speaking, the presence of kidney stones was causally associated with a greater risk of developing osteoporosis (IVW: OR 1.088, CI: 1.015–1.167, P < 0.05). Conclusion The presence of kidney stones is associated with an increased risk of developing osteoporosis. Further prospective cohort studies are needed to validate our results.