Fluoride exposure and risk of fractures: a systematic review and dose-response meta-analysis

Abstract

Abstract Introduction Fluoride (F) is a widespread natural element, whose exposure occurs mostly through drinking water, fluoridated foods and use of toothpastes. At high levels, it may adversely affect human health by altering thyroid and cognitive function in children, and inducing dental and skeletal fluorosis. Since bone health significantly impacts quality of life, we performed a systematic review and meta-analysis to evaluate the effect of F exposure on risk of bone fractures. Methods We conducted a literature search in online databases and selected studies that were carried out in humans and reported risk estimates with 95% confidence intervals for bone fractures according to F exposure. We eventually performed a meta-analysis using a random effects model, comparing the highest versus the lowest exposure, and one-stage dose-response model, to explore the shape of the association. Results Of the 1052 potentially eligible articles, 28 were included in the quantitative analyses. Most studies were conducted in adults (n = 26) and in Western countries (North America=16, Europe=11) and assessed fluoride exposure in drinking water, urine, serum, toenail or diet. The preliminary dose-response curve showed a positive non-linear relation between F exposure through drinking water and bone fracture risk, regardless of site, starting at 1.5 mg/L. Sex-stratified analyses, based on a lower number of studies, showed similar trends, with an indication of higher susceptibility in males compared with females. Conclusions Overall, risk of bone fractures appears to non-linearly increase along with exposure to fluoride in drinking water, regardless of bone site and sex, at levels of exposure above the WHO standard and similar to those that have associated to altered thyroid and cognitive function. Under a public health perspective, fluoride in drinking water should be kept below 1.5 mg/L to prevent bone fractures. Key messages • Our analysis revealed a positive non-linear association between fluoride in drinking water and bone fracture risk. • Public Health actions should be oriented in keeping fluoride in drinking water below 1.5 mg/L to prevent bone fractures.