Objective:This study was aimed to explore the associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children.Methods:A total of 502 children aged 7 - 12 years were selected by cluster sampling from 4 primary schools in Tongxu County, Kaifeng City, Henan Province from April to May 2017. Morning urine and fasting peripheral blood samples were collected from each participant. Urinary fluoride concentration was determined by fluoride ion selective electrode method. Serum calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), calcitonin (CT) and parathyroid hormone (PTH) levels were measured using an automatic biochemical analyzer. Dean method was used to evaluate the prevalence of dental fluorosis in children, and the participants were divided into dental fluorosis group ( n = 173) and control group ( n = 329) after being diagnosed by trained physicians for their dental fluorosis. The associations between the risk of dental fluorosis and the serum biomarkers of bone metabolism in children were analyzed by logistic regression. Results:The levels of serum phosphorus (mmol/L: 1.54 ± 0.19 vs 1.58 ± 0.21) and OC (ng/ml: 11.59 ± 5.22 vs 12.78 ± 5.88) in children in dental fluorosis group were significantly lower than those in children in control group ( P < 0.05). Logistic regression analysis showed that serum OC level affected the risk of dental fluorosis [odds ratio ( OR) = 0.96, 95% confidence interval ( CI): 0.92 - 0.99, P < 0.05]. The relative contribution of the biomarkers of bone metabolism to the risk of dental fluorosis in descending order were serum OC (36.34%), phosphorus (25.89%), BALP (13.16%), PTH (9.73%), calcium (9.44%), CT (3.72%) and ALP (1.72%). Conclusions:The prevalence of dental fluorosis in children is related to the changes of serum biomarkers of bone metabolism. Serum OC plays an important role in the occurrence of dental fluorosis.

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)