Background: Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water ( , the maximum recommended by the World Health Organization) have been inconclusive. Objective: We assessed associations of fluoride in urine, and intake via diet and drinking water, with BMD and fracture incidence in postmenopausal women exposed to drinking water fluoride . Methods: Data were from participants in the Swedish Mammography Cohort–Clinical, a population-based prospective cohort study. At baseline (2004–2009), fluoride exposure was assessed based on urine concentrations ( ) and estimated dietary intake (including drinking water) ( ), and BMD was measured using dual energy X-ray absorptiometry. Incident fractures were ascertained via register-linkage through 2017. Residential history was collected to identify women with long-term consistent drinking water exposures prior to baseline. Results: At baseline, mean urine fluoride was creatinine ( ) and mean dietary intake was ( ), respectively. During follow-up, 850, 529, and 187 cases of any fractures, osteoporotic fractures, and hip fractures, respectively, were ascertained. Baseline BMD was slightly higher among women in the highest vs. lowest tertiles of exposure. Fluoride exposures were positively associated with incident hip fractures, with multivariable-adjusted hazard ratios of 1.50 (95% CI: 1.04, 2.17) and 1.59 (95% CI: 1.10, 2.30), for the highest vs. lowest tertiles of urine fluoride and dietary fluoride, respectively. Associations with other fractures were less pronounced for urine fluoride, and null for dietary fluoride. Restricting the analyses to women with consistent long-term drinking water exposures prior to baseline strengthened associations between fractures and urinary fluoride. Discussion: In this cohort of postmenopausal women, the risk of fractures was increased in association with two separate indicators of fluoride exposure. Our findings are consistent with RCTs and suggest that high consumption of drinking water with a fluoride concentration of may increase both BMD and skeletal fragility in older women. https://doi.org/10.1289/EHP7404

Evidence from observational studies suggests that increased exposure to calcium may increase the risk of coronary heart disease and stroke whereas magnesium might have a protective effect on disease risk. However, studies of the associations of these minerals with heart failure are scarce and limited by potential biases introduced by confounding and reverse causality. We applied a two-sample Mendelian randomization design using summary estimates to assess whether serum calcium and magnesium concentrations are causally associated with heart failure. Summary statistics data were collected for seven and six single-nucleotide polymorphisms associated with calcium and magnesium, respectively, from the hitherto largest genome-wide association studies on these minerals. Corresponding summary statistics for genetic associations with heart failure were available from publicly available data based on the UK Biobank study and based on participants of European ancestry. The findings showed that neither serum calcium nor magnesium concentrations were associated with heart failure. In the standard inverse-variance weighted analysis, the odds ratios of heart failure per genetically predicted one standard deviation increase in mineral concentrations were 0.89 (95% confidence interval 0.67–1.17; p = 0.41) for serum calcium and 0.89 (95% confidence interval 0.72–1.10; p = 0.28) for serum magnesium. Results were robust in sensitivity analyses, including the weighted median and Mendelian randomization Egger analyses. In conclusion, these findings do not support previous findings suggesting a link between serum calcium and magnesium and heart failure, but this study was underpowered to detect weak associations.

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