Jordan R Kuiper1, Joseph M Braun2, Antonia M Calafat3, Bruce P Lanphear4, Kim M Cecil5, Aimin Chen6, Yingying Xu7, Kimberly Yolton7, Heidi J Kalkwarf7, Jessie P Buckley8. 1. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 2. Department of Epidemiology, Brown University, Providence, RI, USA. 3. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. 4. Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada. 5. Department of Radiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 6. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 7. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 8. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: jbuckl19@jhu.edu.
Abstract
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.
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.
Authors: Astrid K Stunes; Irene Westbroek; Björn I Gustafsson; Reidar Fossmark; Jan H Waarsing; Erik F Eriksen; Christiane Petzold; Janne E Reseland; Unni Syversen Journal: BMC Endocr Disord Date: 2011-05-26 Impact factor: 2.763
Authors: Carmen Streicher; Alexandra Heyny; Olena Andrukhova; Barbara Haigl; Svetlana Slavic; Christiane Schüler; Karoline Kollmann; Ingrid Kantner; Veronika Sexl; Miriam Kleiter; Lorenz C Hofbauer; Paul J Kostenuik; Reinhold G Erben Journal: Sci Rep Date: 2017-07-25 Impact factor: 4.379
Authors: Unni Syversen; Astrid K Stunes; Björn I Gustafsson; Karl J Obrant; Lars Nordsletten; Rolf Berge; Liv Thommesen; Janne E Reseland Journal: BMC Endocr Disord Date: 2009-03-30 Impact factor: 2.763