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An analysis of data from a long-term study of environmental contaminants found concerning associations between certain “forever chemicals” and bone development in children and adolescents, researchers reported.

Higher serum concentrations of perfluorooctanoic acid (PFOA) were associated with lower bone mineral density (BMD) at the one third distal radius of the forearm, particularly at age 12 years, according to Jessie P. Buckley, PhD, MPH, of the University of North Carolina at Chapel Hill, and colleagues.

The findings add to growing evidence suggesting that exposure to per- and polyfluoroalkyl substances (PFASs), particularly PFOA, may negatively affect adolescent bone health.

“Exposure to PFAS around this important time for laying down bone could be contributing to less accrual and less bone mass, and that could be important for fractures or later life health outcomes like osteoporosis,” Buckley told Medscape Medical News.

The findings were published in the Journal of the Endocrine Society.

Hazardous Associations

Researchers measured blood concentrations of several PFASs, including PFOA, perfluorohexane sulfonic acid (PFHxS), perfluoroctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA). Samples were obtained at delivery via cord blood, and at ages 3, 8, and 12 years.

The strongest adjusted associations between PFOA exposure and lower one third distal radius Z-scores were observed at age 3 years for boys (beta-coefficient, -0.93) and at age 12 years for girls (beta-coefficient, -0.74).

Higher PFOA concentrations were consistently associated with lower one third distal radius BMD at delivery (beta-coefficient, -0.39), 3 years (beta-coefficient, -0.36), 8 years (beta-coefficient, -0.54), and 12 years (beta-coefficient, -0.40).

Results for other PFASs were mixed. Higher PFHxS and PFOS concentrations at age 3 years were significantly associated with higher whole-body, total hip, and femoral neck BMD Z-scores, whereas higher PFNA concentrations at age 12 years were associated with lower BMD Z-scores.

More research is needed to determine whether these associations persist or evolve into adulthood, the authors noted.

The HOME Study’s Influential Reach

For this study, Buckley and colleagues made new use of data collected through the HOME study.

Their paper is one of more than 200 scientific publications generated from the HOME study. This is a rare long-term investigation of the effects of environmental pollutants on children, Kimberly Yolton, PhD, professor of pediatrics at Cincinnati Children’s at the University of Cincinnati College of Medicine in Cincinnati, and the HOME study’s principal investigator, told Medscape Medical News.

Launched in 2003, the HOME study has expanded substantially in scope over time. It began as an observational study of common environmental exposures and included a randomized trial in which families either received home remediation for potential lead hazards or safety interventions to prevent child injury.

HOME researchers recruited 468 women from prenatal practices affiliated with three hospitals in Cincinnati from March 2003 to January 2006. The original aim was to examine the relationships between prenatal exposure to lead, tobacco smoke, mercury, polychlorinated biphenyl, and pesticides and children’s general health and cognitive and behavioral development through age 3 years.

Additional federal funding and foundation grants later allowed investigators to extend follow-up of the children enrolled in the study. Participants have since completed assessments through age 18 years.

What to Make of PFAS Research

Because of their oil- and water-repellent properties, PFAS have been used since the 1940s in thousands of products, ranging from nonstick cookware to firefighting foams.

Concerns about PFAS exposure arose in the late 1990s following reports of contamination linked to a manufacturing plant in West Virginia. Subsequent research has documented how widespread PFAS exposure has become. According to the CDC, at least one PFAS was detected in more than 99% of samples collected during the 1999-2000 National Health and Nutrition Examination Survey cycle.

Groups such as the American Academy of Pediatrics (AAP) offer guidance on reducing PFAS exposure while cautioning against routine PFAS blood testing.

“Routine measurement of serum PFAS is not recommended as the results do not provide clinical information to guide medical management or predict future health effects,” the AAP stated. “However, if a family is known to have been chronically exposed to high levels of PFAS in drinking water or other sources, the clinician should have a discussion with them, weighing their preferences and the advisability of such testing.”

The AAP also noted that regardless of PFAS blood level, “the best next step for concerned patients is to reduce future sources of exposure.”

“There are currently no evidence-based treatments for removal of PFAS from the body,” the organization stated.

A panel convened by the National Academies of Sciences, Engineering, and Medicine (NASEM) offered similar guidance in a 2022 report. Among the committee’s challenges was determining who would benefit from PFAS testing.

“For example, determining that an individual had a harmful environmental exposure might not help that person but could lead to broader public health measures that could protect the community,” the committee wrote in its report.

The report also advised clinicians caring for patients in regions with known PFAS contamination to explain the limitations of current testing, given that the test results cannot reliably predict whether an individual will develop a particular condition.

Alex R. Kemper, MD, MPH, MS, division chief of primary care pediatrics at Nationwide Children’s Hospital in Columbus, Ohio, served on the NASEM committee and shared a clinician’s perspective to those discussions.

Speaking with Medscape Medical News, Kemper contrasted the evolving PFSA evidence base with the much clearer guidance available to clinicians on lead exposure testing and interventions.

“We don’t have that same story yet for the forever chemicals,” Kemper said. “That may develop over time, but at this point, there are still questions about exactly which chemicals you should test for, where to get that testing done, and what are the right interventions based on the results.”

Research such as Buckley and colleagues’ highlights the need for continued efforts to reduce PFAS exposure at a societal level, Kemper added.

“Families can be a powerful voice of advocacy for PFAS regulation and legislation,” he said. “The lack of information about testing and treatment underscores the important role of preventing exposure.”

Among the study authors, Joseph Braun reported receiving financial compensation as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water. Bruce P. Lanphear served as an expert witness in cases related to childhood lead poisoning but was not personally compensated. Buckley and the other authors reported no actual or potential competing financial interests. Kemper reported having no relevant financial disclosures.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She has covered medical research and healthcare policy for more than 20 years.