Joint effects of phenol, chlorophenol pesticide, phthalate, and polycyclic aromatic hydrocarbon on bone mineral density: comparison of four statistical models

Exposure to phenols, phthalates, pesticides, and polycyclic aromatic hydrocarbons (PAHs) can harm the skeleton. However, data about the joint effects of these chemicals’ mixture on bone health are limited. The final analysis involved 6766 participants aged over 20 years recruited from the National Health and Nutrition Examination Survey. Generalized linear regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were performed to investigate the association of the urinary levels of chemicals (three phenols, two chlorophenol pesticides, nine phthalates, and six polycyclic aromatic hydrocarbon [PAH] metabolites) with bone mineral density (BMD) measurements and osteoporosis (OP) risk. Generalized linear regression identified that benzophenone-3, 2,4-dichlorophenol, mono-n-butyl phthalate, 1-napthol, 3-fluorene, 2-fluorene, and 1-phenanthrene were significantly associated with lower BMD and increased OP risk. The WQS index was negatively associated with total femur, femoral neck, and lumbar spine vertebra 1 (L1) BMD among all the participants, with corresponding β (95% confidence interval) values of −0.028 g/cm 2 (−0.040, −0.017), −0.015 g/cm 2 (−0.025, −0.004), and −0.018 g/cm 2 (−0.033, −0.003). In the BKMR analysis, the overall effect of the mixture was significantly associated with femoral neck BMD among males and OP risk among females. The qgcomp model found a significant association between co-exposure and L1 BMD among all the participants and among males. Our study presents compelling epidemiological evidence that co-exposure to phenols, chlorophenol pesticides, phthalates, and PAHs is associated with reduced BMD and elevated OP risk. It provides epidemiologic evidence for the detrimental effects of these chemicals on bone health.