PMID- 34740813 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20230322 IS - 1873-2763 (Electronic) IS - 8756-3282 (Print) IS - 1873-2763 (Linking) VI - 154 DP - 2022 Jan TI - 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. PG - 116251 LID - S8756-3282(21)00417-8 [pii] LID - 10.1016/j.bone.2021.116251 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Kuiper, Jordan R AU - Kuiper JR AD - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. FAU - Braun, Joseph M AU - Braun JM AD - Department of Epidemiology, Brown University, Providence, RI, USA. FAU - Calafat, Antonia M AU - Calafat AM AD - Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. FAU - Lanphear, Bruce P AU - Lanphear BP AD - Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada. FAU - Cecil, Kim M AU - Cecil KM AD - 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. FAU - Chen, Aimin AU - Chen A AD - Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. FAU - Xu, Yingying AU - Xu Y AD - Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Yolton, Kimberly AU - Yolton K AD - Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Kalkwarf, Heidi J AU - Kalkwarf HJ AD - Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Buckley, Jessie P AU - Buckley JP AD - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: jbuckl19@jhu.edu. LA - eng GR - R01 ES030078/ES/NIEHS NIH HHS/United States GR - R01 ES027224/ES/NIEHS NIH HHS/United States GR - L40 ES032257/ES/NIEHS NIH HHS/United States GR - P01 ES011261/ES/NIEHS NIH HHS/United States GR - P30 ES006096/ES/NIEHS NIH HHS/United States GR - R01 ES025214/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20211102 PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Environmental Pollutants) RN - 0 (Phthalic Acids) RN - 6O7F7IX66E (phthalic acid) SB - IM MH - Adolescent MH - Bayes Theorem MH - *Bone Density MH - Child MH - *Environmental Pollutants/urine MH - Female MH - Humans MH - Male MH - Outcome Assessment, Health Care MH - Phthalic Acids MH - Pregnancy MH - Prospective Studies PMC - PMC8671261 MID - NIHMS1754525 OTO - NOTNLM OT - Adolescence OT - Bone mineral content OT - Bone mineral density OT - Phthalates OT - Pregnancy COIS- Declaration of competing financial interests Dr. Braun's institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; but he has not personally received any compensation for these services. Dr. Lanphear served as an expert witness in cases related to childhood lead poisoning, but he has not personally received any compensation for these services. The other authors declare they have no actual or potential competing financial interests. EDAT- 2021/11/07 06:00 MHDA- 2022/03/12 06:00 PMCR- 2023/01/01 CRDT- 2021/11/06 05:35 PHST- 2021/09/13 00:00 [received] PHST- 2021/10/22 00:00 [revised] PHST- 2021/10/29 00:00 [accepted] PHST- 2021/11/07 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/11/06 05:35 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - S8756-3282(21)00417-8 [pii] AID - 10.1016/j.bone.2021.116251 [doi] PST - ppublish SO - Bone. 2022 Jan;154:116251. doi: 10.1016/j.bone.2021.116251. Epub 2021 Nov 2.