Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density:​ the Health Outcomes and Measures of the Environment (HOME) study

Kuiper, Jordan R.; Braun, Joseph M.; Calafat, Antonia M.; Lanphear, Bruce P.; Cecil, Kim M.; Chen, Aimin; Xu, Yingying; Yolton, Kimberly; Kalkwarf, Heidi J.; Buckley, Jessie P.

Affiliations

¹Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

²Department of Epidemiology, Brown University, Providence, RI, USA

³Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA

⁴Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada

⁵Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

⁶Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

⁷Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA

Abstract and keywords

Background: The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce.

Objectives: To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort.

Methods: We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26 weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12 years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation.

Results: In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: −0.13, 1.10) greater ultradistal radius BMD Z-score in females.

Discussion: In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

Keywords: Bone mineral content; Bone mineral density; Phthalates; Adolescence; Pregnancy

Links

DOI: 10.1016/j.bone.2021.116251

PubMed: 34740813

WoS: 000717964700015

History

Received: 2021-09-13

Revised: 2021-10-22

Accepted: 2021-10-29

Online: 2021-11-2

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