Association between relatively low fluoride exposure and bone mineral density in children and adolescents: Insights from NHANES and a wistar rat model of fluorosis

This study employed an integrated approach combining a population-based study with animal experiments to evaluate the effects of fluoride exposure on bone mineral density (BMD) in children and adolescents. Population data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle, and a Wistar rat model of fluorosis was established for the animal study. Fluoride concentrations in drinking water, blood, and urine were measured using the ion-selective electrode method. BMD in the population was measured using dual-energy X-ray absorptiometry (DXA), whereas the BMD in rats was measured using digital X-ray imaging. Multivariate linear regression and restricted cubic spline (RCS) models were used to assess the association between fluoride exposure and BMD. Results from the population study showed that water fluoride concentration was inversely associated with BMD in the left arm and left leg. Additionally, urinary fluoride concentration was inversely associated with BMD in the left leg, right arm, and right leg. The RCS model further revealed a nonlinear association between water fluoride concentration and BMD in the left arm. In the animal experiments, urinary fluoride concentration was inversely associated with BMD in the left arm, right leg, and pelvis. Additionally, the RCS model indicated nonlinear associations between urinary fluoride concentration and BMD across the left arm, right leg, and pelvis. This study suggests that fluoride exposure is associated with BMD in multiple skeletal regions in children and adolescents.