A Di Nisio1, M De Rocco Ponce1, A Giadone1, M S Rocca2, D Guidolin3, C Foresta4. 1. Department of Medicine, Operative Unit of Andrology and Medicine of Human Reproduction, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. 2. Istituto di Ricerca Pediatrica (IRP)-Fondazione Città della Speranza, Haematology-Oncology Lab, Padova, Italy. 3. Department of Neurosciences, University of Padova, via Gabelli 65, 35128, Padova, Italy. 4. Department of Medicine, Operative Unit of Andrology and Medicine of Human Reproduction, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy. carlo.foresta@unipd.it.
Abstract
PURPOSE: Perfluoroalkyl substances (PFAS) are a class of endocrine-disrupting chemicals. Toxicological studies indicate that PFAS accumulate in bone tissue and could cause alterations in bone metabolism. The primary objective of this study was to examine the association between PFAS exposure and bone status in a cohort of young men resident in a well-defined area with high PFAS environmental pollution. METHODS: Bone status was assessed in 117 subjects aged 18-21 by quantitative ultrasound (QUS) at the heel. Subjects underwent an accurate medical visit. Socio-demographic characteristics, lifestyle, and medical histories were collected. We also verified the interaction between PFAS and hydroxyapatite by computational modelling. The organic anion-transporting peptide (OATP), the putative transporter of PFAS, was evaluated by qPCR in bone biopsies from femoral heads discarded during arthroplasty in three male subjects. RESULTS: Exposed subjects showed significantly lower stiffness index, which resulted in lower t-score and higher prevalence of subjects at medium-high risk of fracture (23.6%) compared with controls (9.7%). Data from computational modelling suggested that PFOA exhibits a high affinity for hydroxyapatite, since the estimated change in free energy is in the order of that exhibited by bisphosphonates. Finally, we observed consistent expression of OATP1A2 gene in primary human osteoblasts. CONCLUSIONS: This is the first study reporting increased osteoporosis risk in young men exposed to PFAS and provide preliminary information on molecular mechanisms that could explain this observation, in agreement with previous studies on animal models and humans. However, these results must be interpreted with caution given the cross-sectional study design and the small number of cases.
PURPOSE:Perfluoroalkyl substances (PFAS) are a class of endocrine-disrupting chemicals. Toxicological studies indicate that PFAS accumulate in bone tissue and could cause alterations in bone metabolism. The primary objective of this study was to examine the association between PFAS exposure and bone status in a cohort of young men resident in a well-defined area with high PFAS environmental pollution. METHODS: Bone status was assessed in 117 subjects aged 18-21 by quantitative ultrasound (QUS) at the heel. Subjects underwent an accurate medical visit. Socio-demographic characteristics, lifestyle, and medical histories were collected. We also verified the interaction between PFAS and hydroxyapatite by computational modelling. The organic anion-transporting peptide (OATP), the putative transporter of PFAS, was evaluated by qPCR in bone biopsies from femoral heads discarded during arthroplasty in three male subjects. RESULTS: Exposed subjects showed significantly lower stiffness index, which resulted in lower t-score and higher prevalence of subjects at medium-high risk of fracture (23.6%) compared with controls (9.7%). Data from computational modelling suggested that PFOA exhibits a high affinity for hydroxyapatite, since the estimated change in free energy is in the order of that exhibited by bisphosphonates. Finally, we observed consistent expression of OATP1A2 gene in primary human osteoblasts. CONCLUSIONS: This is the first study reporting increased osteoporosis risk in young men exposed to PFAS and provide preliminary information on molecular mechanisms that could explain this observation, in agreement with previous studies on animal models and humans. However, these results must be interpreted with caution given the cross-sectional study design and the small number of cases.
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