Sodium Intake and Osteoporosis Risk: Evidence From NHANES and Mendelian Randomization Analysis

Osteoporosis remains a critical public health challenge worldwide, particularly for older adults. Dietary sodium intake is considered a potentially modifiable factor related to bone mineral density (BMD) and osteoporosis risk, but existing findings remain inconsistent, and large-scale evidence is limited. This study combines cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) with Mendelian randomization (MR) to investigate the association and potential causal relationship between sodium intake and osteoporosis. Drawing on NHANES data from the 2005-2010, 2013-2014, and 2017-2018 cycles (n = 3350), we applied weighted multivariable logistic regression to evaluate the association between sodium intake and osteoporosis risk. Leveraging sodium metabolism-related single-nucleotide polymorphisms (SNPs) as instrumental variables, we performed two-sample Mendelian randomization (MR) analysis. MR estimates were derived using inverse-variance weighting (IVW), MR-Egger regression, and weighted median methods, with robustness assessed using pleiotropy tests and leave-one-out sensitivity analysis. Cross-sectional analysis showed that each 1 mg/day increase in two-day average dietary sodium intake was associated with approximately 0.011% lower odds of osteoporosis (OR = 0.99989, 95% CI: 0.99979-1.0000). Compared with the lowest quartile (Q1), participants in Q3 (OR = 0.48, 95% CI: 0.30-0.78, p = 0.004) and Q4 (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028) had lower odds of osteoporosis (p-trend < 0.05). MR analysis using the IVW method provided genetic evidence supporting a potential inverse association (OR = 0.51, 95% CI: 0.28-0.95), although the MR-Egger estimate was nonsignificant and had a wide confidence interval (p = 0.312). These findings support a potential inverse association between sodium intake and osteoporosis risk in this study population. Further prospective and experimental studies are needed to validate these findings, clarify the underlying mechanisms, and determine whether they have any implications for dietary recommendations.