Association of Maternal Bone Resorption with Urinary Fluoride Levels During Pregnancy

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Abstract
Evidence is accumulating linking prenatal fluoride exposure with adverse neurodevelopment. Maternal urinary fluoride (MUF) is a well-established biomarker of fluoride exposure. Because most fluoride is stored in calcified tissues, pregnancy-associated changes in bone metabolism may contribute to fetal fluoride exposure. We evaluated whether maternal bone resorption, indexed by urinary N-telopeptide of type I collagen (NTX), is associated with MUF across pregnancy. Participants were drawn from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts. Each woman contributed one paired MUF–NTX measurement per trimester. Both biomarkers were creatinine-normalized to account for urine dilution. Trimester-specific generalized linear models with a Gamma distribution estimated associations between NTX and MUF, adjusting for maternal age, birth order, infant birthweight, and cohort. Across the trimesters, MUF was relatively stable (0.89 ± 0.37, 0.91 ± 0.41, and 0.83 ± 0.42 mg/L), whereas NTX increased with gestation (68.0 ± 33.5, 99.0 ± 50.3, and 132.4 ± 65.4 nmol BCE/mM creatinine). Higher NTX was consistently associated with higher MUF: β = 0.00315 (p < 0.0001) in Trimester 1, β = 0.00207 (p = 0.001) in Trimester 2, and β = 0.00253 (p < 0.0001) in Trimester 3, corresponding to 11%, 11%, and 18% higher MUF per 1-SD increase in NTX. Results were unchanged after adjustment for estimated fluoride intake, with no evidence of non-linearity. Maternal bone resorption was independently associated with MUF, consistent with a skeletal contribution to urinary fluoride. Research may be needed on measures that can blunt bone mobilization of fluoride during pregnancy.
Funding Information
  • U.S. National Institutes of Healthh (R01ES021446)
  • U.S. National Institutes of Healthh (R01-ES007821)
  • National Institute of Environmental Health Sciences (P01ES022844)
  • National Institute of Environmental Health Sciences (RD83543601)
  • National Institute of Environmental Health Sciences (P42-ES005947)
  • National Institute of Environmental Health Sciences (P20ES018171)
  • National Institute of Environmental Health Sciences (P30ES017885)
  • National Institute of Public Health/Ministry of Health of Mexico

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