Associations of PFAS concentrations during pregnancy and midlife with bone health in midlife: Cross-sectional and prospective findings from Project Viva

Pi-I Debby Lin, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Andres Cardenas, Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
Lisa B. Rokoff, Center for Interdisciplinary Population & Health Research, MaineHealth Institute for Research, Westbrook, ME, USA.
Sheryl L. Rifas-Shiman, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Mingyu Zhang, Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Julianne Botelho, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Antonia M. Calafat, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Diane R. Gold, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Ami R. Zota, Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
Tamarra James-Todd, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Russ Hauser, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Thomas F. Webster, Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
Emily Oken, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abby F. Fleisch, Center for Interdisciplinary Population & Health Research, MaineHealth Institute for Research, Westbrook, ME, USA; Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA. Electronic address: Abby.Fleisch@mainehealth.org.

Abstract

BACKGROUND: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown. METHODS: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife. RESULTS: Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g. , PFOA: 1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women. DISCUSSION: Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.