Higher frequency of adding salt to foods increases the risk of low bone mineral density in individuals over 60 - A Mendelian randomization study

Background: Adding salt to foods is associated with an increased osteoporosis risk, but the causality of this relationship remains unknown. Methods: in this study, we conducted a two-sample Mendelian randomization (MR) study to investigate the potential causal effect of adding salt to foods on bone mineral density (BMD). Utilizing data from the UK Biobank to estimate adding salt to foods based on self-reported consumption and genetic association data for BMD from the Genetic Factors for Osteoporosis (GEFOS) consortium, we examined various BMD sites: forearm (distal 1/3 radius), lumbar spine (L1-4), femoral neck, total body BMD (TB-BMD), and age-specific TB-BMD (0-15, 15-30, 30-45, 45-60, and over 60 years). The primary analysis used the inverse variance weighted method, supplemented by sensitivity analyses employing multiple MR methods, MR-PRESSO, and leave-one-out approach. Pleiotropy and heterogeneity were assessed using MR-Egger intercept, funnel plots, Cochran's Q, and Rucker's Q. Results: we found a suggestive association between higher frequency of adding salt to foods and decreased TB-BMD in Europeans over 60 (OR = 0.84, 95 % CI = 0.721-0.979, p = 0.026). This association remained robust across different methods and sensitivity analyses, showing no apparent heterogeneity or pleiotropy. However, no causal effect was detected on BMD in other age groups or skeletal sites. Conclusion: this MR study suggests a higher frequency of adding salt to foods significantly increases low BMD risk in individuals over 60, underscoring the importance of reducing salt consumption in this demographic for osteoporosis prevention.