Correlations between bone metabolism biomarkers and fluoride exposure in adults and children

Abstract

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P⁵⁺), and calcium (Ca²⁺). For adults, the biomarkers included ALP, CT, PTH, β-CrossLaps (β-CTX), P⁵⁺, and Ca²⁺. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P⁵⁺ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P⁵⁺, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between β-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca²⁺, β-CTX, and PTH contents. There was a non-linear correlation between serum Ca²⁺, P⁵⁺, and β- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P⁵⁺ levels can serve as sensitive bone metabolism biomarkers in children, while β-CTX, P⁵⁺, and Ca²⁺ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

Keywords: Bone metabolism; Dose–effect relationship; Fluoride; Threshold effect.