The association of fluoride exposure with bone density and fracture risk: a dose-response meta-analysis
Abstract
BACKGROUND: Fluoride exposure and its effects on human health are controversial and highly debated. While beneficial in preventing dental caries, fluoride has been linked to skeletal and dental fluorosis at high levels, as well as other adverse health endpoints in children and adults. However, the safe range of exposure for bone health remains poorly defined. We used existing literature to quantify the dose-response relation between fluoride exposure and bone health, focusing on fracture risk and bone mineral density (BMD). METHODS: We conducted a systematic review and dose-response meta-analysis by searching literature in online databases (MEDLINE/PubMed, Embase and Web of Science) up to August 26, 2025, and by pooling results of studies examining fluoride exposure and its associations with bone health outcomes, namely fracture risk and BMD. We also conducted stratified analyses by sex, age, and fracture site. This study is registered in PROSPERO (CRD42022321899). RESULTS: We included 37 studies published between 1945 and 2024. 10 pertained to bone density only; 19 to bone fractures only; and eight to both outcomes. We found a non-linear, positive relation between fluoride exposure and fracture risk, with an indication of an approximate threshold around 1.5 mg/L of fluoride in drinking water and a nearly linear increasing fracture risk above that concentration (risk ratios of 1.06, 1.19 and 1.35 at 2.0, 3.0 and 4.0 mg/L, respectively, compared to null exposure).…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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