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

Cited Works (6)

Year	Entry
1990	Riggs BL, Hodgson SF, O'Fallon WM, Chao EYS, Wahner HW, Muhs JM, Cedel SL, Melton LJ III. Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. NEJM. March 22, 1990;322(12):802-809.
1994	Fratzl P, Roschger P, Eschberger J, Abendroth B, Klaushofer K. Abnormal bone mineralization after fluoride treatment in osteoporosis: a small‐angle x‐ray‐scattering study. J Bone Miner Res. October 1994;9(10):1541-1549.
2012	Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab. November 2012;23(11):576-581.
2016	Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O’Karma M, Wallace TC, Zemel BS. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. April 2016;27(4):1281-1386.
2011	Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Frederick MM, Huang X, Lu M, Mahboubi S, Hangartner T, Winer KK. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. October 2011;96(10):3160-3169.
2014	Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson‐Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. November 2014;29(11):2520-2526.