Thursday, April 3, 2025
4/3/2025
Serum PFAS and risk of fracture and bone loss - PROJECT SUMMARY With aging of the U.S. population, the burden of osteoporotic fractures will increase well beyond the current estimate of 2 million per year and $17 billion cost. The 10-year absolute risk of fracture for those aged 75-84 is 24% in women and 14% in men. PFAS are chemicals that are stable in the environment and can bioaccumulate in human tissue. Biomonitoring studies document PFAS exposure in >98% of the U.S. population, with up to 200 million Americans exposed to PFAS through their drinking water. PFAS have been isolated in human bone and may be linked to osteoporosis and increased risk of fracture; these concerning findings need to be verified in additional cohorts. Rigorous epidemiologic studies are critically needed to understand the impact of PFAS on bone health, especially those that include racially diverse populations. Our overarching hypothesis is that PFAS concentrations are associated with increased bone loss and fracture risk. We will leverage existing samples and data from the two largest prospective US osteoporosis cohort studies to perform an in-depth study of serum PFAS, bone loss, and fractures that will include long-term follow-up of up to 20 years using: 1) The Osteoporotic Fractures in Men (MrOS) Study and 2) the Study of Osteoporotic Fractures (SOF). Additionally, we will confirm findings in the Health Aging and Body Composition Study (HABC), a racially diverse cohort of older adults. Aim 1: Using efficient case-cohort study designs, investigate the prospective association between serum PFAS and incident fractures in 1321 MrOS men and 1578 SOF women who will be sex matched with 1500 randomly selected persons from each respective cohort. PFAS will be analyzed in serum. We will confirm findings in a third case-cohort selected from the racially diverse HABC study (479 incident fractures and a sex- and race- matched cohort of 480 randomly selected participants). Aim 2: Evaluate the prospective association between serum PFAS and rate of loss of total hip bone mineral density (BMD) separately in men and women from the three subcohorts. Aim 3: Utilize markers of bone metabolism and structure to provide novel insights into the cellular and structural mechanisms by which PFAS may adversely affect bone. #3a: Evaluate the association between serum PFAS and markers of bone formation (PINP) and bone resorption (CTX) separately in men and women from the cohorts. #3b: In a substudy using data already available in MrOS, evaluate the association between serum PFAS and bone structure (HR-pQCT). #3c: Also, in an exploratory sub-Aim, apply mediation analyses using a counterfactual framework-based approach to estimate the extent to which PFAS’s influence on bone loss might be mediated via biomarkers of bone metabolism (serum PINP, CTX). Aim 4: Leverage rich data on urine Cd exposure in this study population to investigate mixtures of PFAS and Cd in the preceding analyses. We have an excellent opportunity to capitalize on pre-existing data and biospecimens to conduct a rigorous evaluation of the associations between PFAS and fracture risk, bone mineral density, and bone turnover in a diverse study population.
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