Associations between mixed urinary phenols and parabens metabolites and bone mineral density: Four statistical models

Phenols and parabens widely exist in personal care and consumer products and have been proved to be endocrine disrupting chemicals that could disturb bone metabolism. The current studies focusing on the associations between phenols and parabens with bone mineral density (BMD) drew contradictory conclusions. Considering the bias might be due to not considering the effects of mixed exposure, we conducted the first cross-sectional study to investigate the associations of both single and mixed metabolites of phenols and parabens with BMD in three populations by setting up four models: generalized linear regression model (GLM), weighted quantile sum (WQS) regression model, quantile g-computation (qgcomp) model and Bayesian kernel machine regression (BKMR) model, based on the US National Health and Nutrition Examination Survey (NHANES) database. We found that the association between the mixtures and total femur BMD in men was significantly negative. Bisphenol A (BPA) was shown to play the most important role in this negative association in the BKMR model, and this negative association was also confirmed in the GLM model with β coefficient (95% CI) being -0.02 (-0.04, -0.01). The relationships between the mixtures and femoral neck and trochanter BMD in postmenopausal women were significantly positive. Benzophenone-3 (BP-3) played the most significant role in the positive association with trochanter BMD, as confirmed by the WQS, qgcomp and BKMR models, and this positive association was also verified by the GLM model with β coefficient (95% CI) being 0.01 (0.00, 0.02). In conclusion, the association between the mixed phenols and parabens and BMD was negative in men while was positive in postmenopausal women, which was gender-specific. This study might provide new ideas for the prevention and treatment of osteoporosis and the control of personal care and consumer products containing phenols and parabens in the future.