Gestational phthalate exposures and bone mineral density in early adolescence: the HOME Study

Abstract

Background/Aim: Phthalate exposures have been associated with lower areal bone mineral density (aBMD) and osteoporosis in adults. Although early life may be a period of heightened susceptibility to environmental osteotoxicants, we are unaware of any studies of phthalate exposures in utero and aBMD in children. Thus, we examined gestational phthalate exposures and early adolescent aBMD in a prospective birth cohort study. Methods: We used data from 225 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003-2006. We measured monobutyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and four metabolites of di-2-ethylhexyl phthalate (DEHP) in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We measured children’s femoral neck, distal forearm (1/3 radius), spine, total hip, and total body (excluding head) aBMD with dual x-ray absorptiometry at 12 years of age and calculated height-, age-, sex-, and race-specific aBMD z-scores. We estimated covariate-adjusted associations per 2-fold increase in maternal urinary phthalate concentrations and assessed effect measure modification (EMM) by child’s sex using sex-stratified models. Results: In adjusted analyses, higher MCPP and MEP concentrations were associated with greater aBMD at all sites with estimates generally stronger for MCPP. For example, associations of MCPP and MEP concentrations with total hip aBMD z-score were 0.16 (95% CI: 0.01, 0.32) and 0.09 (95% CI: 0.01, 0.17), respectively. Sex modified urinary MEP and MiBP concentration’s associations with spine aBMD. Higher MEP concentrations were associated with greater spine aBMD z-score in males (β = 0.19, 95% CI: 0.09, 0.30; EMM p-value 0.06) while higher MiBP concentrations were associated with greater spine aBMD z-score in females (β = 0.24, 95% CI: 0.07, 0.41; EMM p-value 0.07). Conclusions: Gestational phthalate exposures may increase bone mineral density in early adolescence.