Exposure to perfluoroalkyl substances and longitudinal changes in bone mineral density in adolescents and young adults: A multi-cohort study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood. OBJECTIVES: To examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic). METHODS: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were measured at baseline and dual x-ray absorptiometry scans were performed at baseline and follow-up to measure BMD. We estimated longitudinal associations between BMD and five PFAS via separate covariate-adjusted linear mixed effects models, and between BMD and the PFAS mixture via quantile g-computation. RESULTS: In SOLAR adolescents, baseline plasma perfluorooctanesulfonic acid (PFOS) was associated with longitudinal changes in BMD. Each doubling of PFOS was associated with an average -0.003 g/cm2 difference in change in trunk BMD per year over follow-up (95% CI: -0.005, -0.0002). Associations with PFOS persisted in CHS young adults, where each doubling of plasma PFOS was associated with an average -0.032 g/cm2 difference in total BMD at baseline (95% CI -0.062, -0.003), though longitudinal associations were non-significant. We did not find associations of other PFAS with BMD; associations of the PFAS mixture with BMD outcomes were primarily negative though non-significant. DISCUSSION: PFOS exposure was associated with lower BMD in adolescence and young adulthood, important periods for bone development, which may have implications on future bone health and risk of osteoporosis in adulthood.

Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps. OBJECTIVE: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies. METHODS: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7th, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis. RESULTS: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all ß [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (pone-tailed = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (pone-tailed = 0.02) and paraoxonase-1 (pone-tailed = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase. CONCLUSIONS: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity.