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.