Serum per- and polyfluoroalkyl substances (PFAS) and bone mineral density in Norwegian adolescents: sex-specific associations and mixture effects

BACKGROUND: Adolescence is the critical period for the development of peak bone mass. Per- and polyfluoroalkyl substances (PFAS) are widespread endocrine disruptors that may disturb skeletal development, but evidence in Nordic adolescents is limited. OBJECTIVES: To evaluate sex-specific associations between serum PFAS and areal bone mineral density (aBMD) Z-scores among Norwegian adolescents. METHODS: This cross-sectional study utilised data from Fit Futures 1 (2010-2011), a cohort of adolescents in Northern Norway. Eighteen serum PFAS were quantified, and aBMD Z-scores (femoral neck, total hip, total body) were calculated using dual-energy X-ray absorptiometry. We used multivariable linear regression and mixture analyses (quantile g-computation and Bayesian kernel machine regression) to estimate sex-specific associations. RESULTS: Among 889 participants (421 girls and 468 boys; mean age 16.2 years), eight PFAS had detection rates >70%. The sum of linear and branched perfluorooctane sulfonic acid (ΣPFOS) had the highest median concentration (6.23 ng/ml). Perfluorononanoic acid (PFNA) (β = -0.16 per doubling, 95% CI: -0.26, -0.06) and perfluorodecanoic acid (PFDA) (β = -0.15 per doubling, 95% CI: -0.24, -0.06) showed consistent inverse association with total body aBMD. Mixture analyses suggested modest inverse overall mixture estimates, but 95% confidence intervals crossed the null. Sex-stratified analyses suggested that estimates tended to be more negative in boys than in girls. CONCLUSIONS: Higher concentrations of several PFAS, particularly PFNA and PFDA, were modestly associated with lower aBMD Z-scores in Norwegian adolescents, most consistently for total body aBMD. Evidence for mixture effects and sex-specific differences was limited, although inverse associations tended to be more pronounced in boys. Longitudinal studies are needed to clarify temporal relationships and long-term skeletal impacts.