Association of Maternal Bone Resorption with Urinary Fluoride Levels During Pregnancy

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.