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Perfluoroalkyl substances and bone health in young men: a pilot study

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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.

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References

  1. J.M. Conder, R.A. Hoke, W. De Wolf, M.H. Russell, R.C. Buck, Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ. Sci. Technol. 42, 995–1003 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. G.W. Olsen, C.C. Lange, M.E. Ellefson, D.C. Mair, T.R. Church, C.L. Goldberg, R.M. Herron, Z. Medhdizadehkashi, J.B. Nobiletti, J.A. Rios, W.K. Reagen, L.R. Zobel, Temporal trends of perfluoroalkyl concentrations in American Red Cross adult blood donors, 2000–2010. Environ. Sci. Technol. 46, 6330–6338 (2012). https://doi.org/10.1021/es300604p

    Article  CAS  PubMed  Google Scholar 

  3. C. Kubwabo, I. Kosarac, K. Lalonde, Determination of selected perfluorinated compounds and polyfluoroalkyl phosphate surfactants in human milk. Chemosphere 91, 771–7 (2013). https://doi.org/10.1016/j.chemosphere.2013.02.011

    Article  CAS  PubMed  Google Scholar 

  4. S. Kim, K. Choi, K. Ji, J. Seo, Y. Kho, J. Park, S. Kim, S. Park, I. Hwang, J. Jeon, H. Yang, J.P. Giesy, Trans-placental transfer of thirteen perfluorinated compounds and relations with fetal thyroid hormones. Environ. Sci. Technol. 45, 7465–7472 (2011). https://doi.org/10.1021/es202408a

    Article  CAS  PubMed  Google Scholar 

  5. C. Foresta, S. Tescari, A. Di Nisio, Impact of perfluorochemicals on human health and reproduction: a male’s perspective. J. Endocrinol. Investig. (2017). https://doi.org/10.1007/s40618-017-0790-z

  6. A. Di Nisio, C. Foresta, Water and soil pollution as determinant of water and food quality/contamination and its impact on male fertility. Reprod. Biol. Endocrinol. 17, 4 (2019). https://doi.org/10.1186/s12958-018-0449-4

    Article  PubMed  PubMed Central  Google Scholar 

  7. A. Koskela, M.A. Finnilä, M. Korkalainen, S. Spulber, J. Koponen, H. Håkansson, J. Tuukkanen, M. Viluksela, Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation. Toxicol. Appl. Pharmacol. 301, 14–21 (2016). https://doi.org/10.1016/j.taap.2016.04.002

    Article  CAS  PubMed  Google Scholar 

  8. L.Y. Lin, L.L. Wen, T.C. Su, P.C. Chen, C.Y. Lin, Negative association between serum perfluorooctane sulfate concentration and bone mineral density in US premenopausal women: NHANES, 2005–2008. J. Clin. Endocrinol. Metab. 99, 2173–2180 (2014). https://doi.org/10.1210/jc.2013-3409

    Article  CAS  PubMed  Google Scholar 

  9. N. Khalil, A. Chen, M. Lee, S.A. Czerwinski, J.R. Ebert, J.C. De Witt, K. Kannan, Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009–2010. Environ. Health Perspect. 124, 81–87 (2016). https://doi.org/10.1289/ehp.1307909

    Article  CAS  PubMed  Google Scholar 

  10. N. Khalil, J.R. Ebert, M. Honda, M. Lee, R.W. Nahhas, A. Koskela, T. Hangartner, K. Kannan, Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8–12 year old children: a pilot study. Environ. Res. 160, 314–321 (2018). https://doi.org/10.1016/j.envres.2017.10.014

    Article  CAS  PubMed  Google Scholar 

  11. Z. Jeddy, J.H. Tobias, E.V. Taylor, K. Northstone, W.D. Flanders, T.J. Hartman, Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17. Arch. Osteoporos. 13, (2018). https://doi.org/10.1007/s11657-018-0498-5

  12. J. Bogdanska, D. Borg, M. Sundström, U. Bergström, K. Halldin, M. Abedi-Valugerdi, Å. Bergman, B. Nelson, J. DePierre, S. Nobel, Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose. Toxicology 284, 54–62 (2011). https://doi.org/10.1016/j.tox.2011.03.014

    Article  CAS  PubMed  Google Scholar 

  13. F. Pérez, M. Nadal, A. Navarro-Ortega, F. Fàbrega, J.L. Domingo, D. Barceló, M. Farré, Accumulation of perfluoroalkyl substances in human tissues. Environ. Int. 59, 354–362 (2013). https://doi.org/10.1016/j.envint.2013.06.004

    Article  CAS  PubMed  Google Scholar 

  14. A. Koskela, J. Koponen, P. Lehenkari, M. Viluksela, M. Korkalainen, J. Tuukkanen, Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation. Sci. Rep. 7, 6841 (2017). https://doi.org/10.1038/s41598-017-07359-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. A. Di Nisio, I. Sabovic, U. Valente, S. Tescari, M.S. Rocca, D. Guidolin, S. Dall’Acqua, L. Acquasaliente, N. Pozzi, M. Plebani, A. Garolla, C. Foresta, Endocrine disruption of androgenic activity by perfluoroalkyl substances: clinical and experimental evidence. J. Clin. Endocrinol. Metab. 104, 1259–1271 (2019). https://doi.org/10.1210/jc.2018-01855

    Article  PubMed  Google Scholar 

  16. Y.M. Weaver, D.J. Ehresman, J.L. Butenhoff, B. Hagenbuch, Roles of rat renal organic anion transporters in transporting perfluorinated carboxylates with different chain lengths. Toxicol. Sci. 113, 305–314 (2010). https://doi.org/10.1093/toxsci/kfp275

    Article  CAS  PubMed  Google Scholar 

  17. N.E. Skakkebaek, E. Rajpert-De Meyts, K.M. Main, Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16, 972–8 (2001)

    Article  CAS  PubMed  Google Scholar 

  18. Veneto Region. Regional Council Resolution, D.G.R. 2133/2016, Annex A and subsequent modifications. (2016). Available at: https://bur.regione.veneto.it/BurvServices/pubblica/DettaglioDgr.aspx?id=336975

  19. M.-A. Krieg, R. Barkmann, S. Gonnelli, A. Stewart, D.C. Bauer, L. Del Rio Barquero, J.J. Kaufman, R. Lorenc, P.D. Miller, W.P. Olszynski, C. Poiana, A.-M. Schott, E.M. Lewiecki, D: Hans, Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J. Clin. Densitom. 11, 163–187 (2008). https://doi.org/10.1016/j.jocd.2007.12.011

    Article  PubMed  Google Scholar 

  20. R.M. Berg, H. Wallaschofski, M. Nauck, R. Rettig, M.R.P. Markus, R. Laqua, N. Friedrich, A. Hannemann, Positive association between adipose tissue and bone stiffness. Calcif. Tissue Int. 97, 40–49 (2015). https://doi.org/10.1007/s00223-015-0008-3

    Article  CAS  PubMed  Google Scholar 

  21. S.L. Greenspan, M.L. Bouxsein, M.E. Melton, A.H. Kolodny, J.H. Clair, P.T. Delucca, M. Stek, K.G. Faulkner, E.S. Orwoll, Precision and discriminatory ability of calcaneal bone assessment technologies. J. Bone Miner. Res. 12, 1303–1313 (1997). https://doi.org/10.1359/jbmr.1997.12.8.1303

    Article  CAS  PubMed  Google Scholar 

  22. P. Hadji, O. Hars, C. Wüster, K. Bock, U.-S. Alberts, H.-G. Bohnet, G. Emons, K.-D. Schulz, Stiffness index identifies patients with osteoporotic fractures better than ultrasound velocity or attenuation alone. Maturitas 31, 221–226 (1999). https://doi.org/10.1016/S0378-5122(99)00003-1

    Article  CAS  PubMed  Google Scholar 

  23. M. Jaworski, M. Lebiedowski, R.S. Lorenc, J. Trempe, Ultrasound bone measurement in pediatric subjects. Calcif. Tissue Int. 56, 368–371 (1995). https://doi.org/10.1007/BF00301604

    Article  CAS  PubMed  Google Scholar 

  24. H. Heinz, T.-J. Lin, R. Kishore Mishra, F.S. Emami, Thermodynamically consistent force fields for the assembly of inorganic, organic, and biological nanostructures: the INTERFACE force field. Langmuir 29, 1754–1765 (2013). https://doi.org/10.1021/la3038846

    Article  CAS  PubMed  Google Scholar 

  25. O. Trott, A.J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455–61 (2010). https://doi.org/10.1002/jcc.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. A. Ferlin, L. Perilli, L. Gianesello, G. Taglialavoro, C. Foresta, Profiling insulin like factor 3 (INSL3) signaling in human osteoblasts. PLoS One. 6, (2011). https://doi.org/10.1371/journal.pone.0029733

  27. K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–8 (2001). https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  28. L.F. Duarte, F.C. Teixeira, R. Fausto, Molecular modeling of the interaction of novel hydroxy- and aminobisphosphonates with hydroxyapatite. Arkivoc 2010, 117 (2009). https://doi.org/10.3998/ark.5550190.0011.512

    Article  Google Scholar 

  29. J.R. Thibodeaux, R.G. Hanson, J.M. Rogers, B.E. Grey, B.D. Barbee, J.H. Richards, J.L. Butenhoff, L.A. Stevenson, C. Lau, Exposure to Perfluorooctane Sulfonate during Pregnancy in Rat and Mouse. I: Maternal and Prenatal Evaluations. Toxicol. Sci. 74, 369–381 (2003). https://doi.org/10.1093/toxsci/kfg121

    Article  CAS  PubMed  Google Scholar 

  30. A.M. Ingelido, A. Abballe, S. Gemma, E. Dellatte, N. Iacovella, G. De Angelis, F. Zampaglioni, V. Marra, R. Miniero, S. Valentini, F. Russo, M. Vazzoler, E. Testai, E. De Felip, Biomonitoring of perfluorinated compounds in adults exposed to contaminated drinking water in the Veneto Region, Italy. Environ. Int. 110, 149–159 (2018). https://doi.org/10.1016/j.envint.2017.10.026

    Article  CAS  PubMed  Google Scholar 

  31. E. Hernlund, A. Svedbom, M. Ivergård, J. Compston, C. Cooper, J. Stenmark, E.V. McCloskey, B. Jönsson, J.A. Kanis, Osteoporosis in the European Union: medical management, epidemiology and economic burden. Arch. Osteoporos. 8, 136 (2013). https://doi.org/10.1007/s11657-013-0136-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. G.I. Baroncelli, Quantitative ultrasound methods to assess bone mineral status in children: technical characteristics, performance, and clinical application. Pediatr. Res. 63, 220–228 (2008). https://doi.org/10.1203/PDR.0b013e318163a286

    Article  PubMed  Google Scholar 

  33. G. Alwis, B. Rosengren, J.Å. Nilsson, S. Stenevi-Lundgren, M. Sundberg, I. Sernbo, M.K. Karlsson, Normative calcaneal quantitative ultrasound data as an estimation of skeletal development in Swedish children and adolescents. Calcif. Tissue Int. 87, 493–506 (2010). https://doi.org/10.1007/s00223-010-9425-5

    Article  CAS  PubMed  Google Scholar 

  34. J. Schalamon, G. Singer, G. Schwantzer, Y. Nietosvaara, Quantitative ultrasound assessment in children with fractures. J. Bone Miner. Res. 19, 1276–1279 (2004). https://doi.org/10.1359/JBMR.040401

    Article  PubMed  Google Scholar 

  35. K.-Y. Chin, S. Ima-Nirwana, Calcaneal quantitative ultrasound as a determinant of bone health status: what properties of bone does it reflect? Int. J. Med. Sci. 10, 1778 (2013). https://doi.org/10.7150/IJMS.6765

    Article  PubMed  PubMed Central  Google Scholar 

  36. B.K. Weeks, R. Hirsch, R.C. Nogueira, B.R. Beck, Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Jt. Res. 5, 538–543 (2016). https://doi.org/10.1302/2046-3758.511.BJR-2016-0116.R1

    Article  CAS  Google Scholar 

  37. Y. Xu, B. Guo, J. Gong, H. Xu, Z. Bai, The correlation between calcaneus stiffness index calculated by QUS and total body BMD assessed by DXA in Chinese children and adolescents. J. Bone Miner. Metab. 32, 159–166 (2014). https://doi.org/10.1007/s00774-013-0474-5

    Article  CAS  PubMed  Google Scholar 

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Correspondence to C. Foresta.

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Di Nisio, A., De Rocco Ponce, M., Giadone, A. et al. Perfluoroalkyl substances and bone health in young men: a pilot study. Endocrine 67, 678–684 (2020). https://doi.org/10.1007/s12020-019-02096-4

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