Abstract
The skeleton forms a dynamic organ system, functioning in a highly metabolic environment continuously affecting the balance between bone resorption and bone formation. Highly differentiated cells and multiple hormonal and molecular pathways are involved in this remodeling process that is unavoidably affected by normal aging. Apart from aging, several factors such as geographic variation, climate conditions, nutritional status, socioeconomic status, culture, pollution, and endocrine disruptors have been suggested to have a direct or indirect impact on bone metabolism and influence bone health. Τhe positive or negative effect of each one of these factors on bone health depends on many variables such as age of exposure, duration of exposure, and intensity of exposure but also on the combined effects of other cofactors. The pathogenetic mechanisms and the molecular pathways by which bone metabolism is affected have not always been clarified. Therefore, in this chapter, we aim to summarize the current literature on the influence of environmental factors on bone metabolism and disease and to review any recent updates in research about the impact of endocrine disruptors on bone health.
This is a preview of subscription content, log in via an institution to check access.
References
Abnosi MH, Shojafar E. Biochemical and morphological changes in bone marrow mesenchymal stem cells induced by treatment of rats with p-Nonylphenol. Iran J Basic Med Sci. 2015;18(4):317–24.
Abnosi MH, Soleimani Mehranjani M, Shariatzadeh MA, Dehdehi L. Para-nonylphenol impairs osteogenic differentiation of rat bone marrow mesenchymal stem cells by influencing the osteoblasts mineralization. Iran J Basic Med Sci. 2012;15(6):1131–9.
Agas D, Sabbieti MG, Capacchietti M, et al. Benzyl butyl phthalate influences actin distribution and cell proliferation in rat Py1a osteoblasts. J Cell Biochem. 2007;101(3):543–51. https://doi.org/10.1002/jcb.21212.
Agas D, Lacava G, Sabbieti MG. Bone and bone marrow disruption by endocrine-active substances. J Cell Physiol. 2019;234(1):192–213. https://doi.org/10.1002/jcp.26837.
Alvaer K, Meyer HE, Falch JA, Nafstad P, Søgaard AJ. Outdoor air pollution and bone mineral density in elderly men – the Oslo health study. Osteoporos Int. 2007;18:1669–74.
Bhat FA, Ramajayam G, Parameswari S, et al. Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts – in vitro. Toxicol Vitr. 2013;27(1):250–6. https://doi.org/10.1016/j.tiv.2012.09.003.
Bjora R, Falch JA, Staaland H, Nordsletten L, Gjengedal E. Osteoporosis in the Norwegian moose. Bone. 2001;29(1):70–3.
Brennan SL, Pasco JA, Urquhart DM, Oldenburg B, Wang Y, Wluka AE. Association between socioeconomic status and bone mineral density in adults: a systematic review. Osteoporos Int. 2011;22(2):517–27.
Brzóska MM, Moniuszko-Jakoniuk J. Low-level exposure to cadmium during the lifetime increases the risk of osteoporosis and fractures of the lumbar spine in the elderly: studies on a rat model of human environmental exposure. Toxicol Sci. 2004;82(2):468–77.
Brzóska MM, Moniuszko-Jakoniuk J. Disorders in bone metabolism of female rats chronically exposed to cadmium. Toxicol Appl Pharmacol. 2005a;202(1):68–83.
Brzóska MM, Moniuszko-Jakoniuk J. Bone metabolism of male rats chronically exposed to cadmium. Toxicol Appl Pharmacol. 2005b;207(3):195–211.
Chang KH, Chang MY, Muo CH, et al. Exposure to air pollution increases the risk of osteoporosis: a nationwide longitudinal study. Medicine (Baltimore). 2015;94(17):e733. https://doi.org/10.1097/MD.0000000000000733.
Chen X, Zhu G, Gu S, Jin T, Shao C. Effects of cadmium on osteoblasts and osteoclasts in vitro. Environ Toxicol Pharmacol. 2009;28(2):232–6.
Chen X, Zhu G, Jin T, Lei L, Liang Y. Bone mineral density is related with previous renal dysfunction caused by cadmium exposure. Environ Toxicol Pharmacol. 2011;32(1):46–53.
Chen X, Zhu G, Jin T. Cadmium stimulates the osteoclastic differentiation of RAW264.7 cells in presence of osteoblasts. Biol Trace Elem Res. 2012;146(3):349–53.
Chiu C-Y, Sun S-C, Chiang C-K, et al. Plasticizer di(2-ethylhexyl)phthalate interferes with osteoblastogenesis and adipogenesis in a mouse model. J Orthop Res. 2017;36(4):1124–34. https://doi.org/10.1002/jor.23740.
Choi JI, Cho HH. Effects of di(2-ethylhexyl)phthalate on bone metabolism in Ovariectomized mice. J Bone Metab. 2019;26(3):169. https://doi.org/10.11005/jbm.2019.26.3.169.
Compston JE, Watts NB, Chapurlat R, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124(11):1043–50.
Coonse KG, Coonts AJ, Morrison EV, Heggland SJ. Cadmium induces apoptosis in the human osteoblast-like cell line Saos-2. J Toxicol Environ Health A. 2007;70(7):575–81.
Dawson-Hughes B, Harris S, Krall E, Dallal G. Effect of calcium and vitamin supplementation on bone density in men and women 65 years of age and older. N Engl J Med. 1997;337:670–6.
DeFlorio-Barker SA, Turyk ME. Associations between bone mineral density and urinary phthalate metabolites among post-menopausal women: a cross-sectional study of NHANES data 2005–2010. Int J Environ Health Res. 2016;26(3):326–45. https://doi.org/10.1080/09603123.2015.1111312.
Demontiero O, Vidal C, Duque G. Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis. 2012;4(2):61–76.
Di Nisio A, De Rocco PM, Giadone A, Rocca MS, Guidolin D, Foresta C. Perfluoroalkyl substances and bone health in young men: a pilot study. Endocrine. 2019;(September):1–7. https://doi.org/10.1007/s12020-019-02096-4.
Du Y, Zhao LJ, Xu Q, Wu KH, Deng HW. Socioeconomic status and bone mineral density in adults by race/ethnicity and gender: the Louisiana osteoporosis study. Osteoporos Int. 2017;28(5):1699–709.
Duque G, Li W, Vidal C, Bermeo S, Rivas D, Henderson J. Pharmacological inhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6 mice. J Bone Miner Res. 2013;28(3):639–48. https://doi.org/10.1002/jbmr.1782.
Engström A, Skerving S, Lidfeldt J, et al. Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D. Res. 2009 Feb;109(2):188–92.
Ersoy B, Kizilay DÖ, Yilmaz SK, Taneli F, Gümüşer G. Bone mineral density, vitamin D status, and calcium intake in healthy female university students from different socioeconomic groups in Turkey. Arch Osteoporos. 2018;13(1):135.
Fader KA, Nault R, Raehtz S, McCabe LR, Zacharewski TR. 2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice. Toxicol Appl Pharmacol. 2018;348:85–98. https://doi.org/10.1016/J.TAAP.2018.04.013.
Finnilä MAJ, Zioupos P, Herlin M, et al. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties. J Biomech. 2010;43(6):1097–103. https://doi.org/10.1016/j.jbiomech.2009.12.011.
Geens T, Aerts D, Berthot C, et al. A review of dietary and non-dietary exposure to bisphenol-a. Food Chem Toxicol. 2012;50(10):3725–40. https://doi.org/10.1016/j.fct.2012.07.059.
Ghezelbash F, Shirazi-Adl A, Plamondon A, et al. Obesity and obesity shape markedly influence spine biomechanics: a subject-specific risk assessment model. Ann Biomed Eng. 2017;45:2373–82.
Gore AC, Chappell VA, Fenton SE, et al. EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36(6):E1–E150. https://doi.org/10.1210/er.2015-1010.
Gracia-Marco L, Ortega FB, Casajús JA, et al. Socioeconomic status and bone mass in Spanish adolescents. The HELENA Study J Adolesc Health. 2012;50(5):484–90.
Guidance on identifying endocrine disruptors published – EFSA.: https://www.efsa.europa.eu/en/press/news/180607.
Hagiwara H, Sugizaki T, Tsukamoto Y, Senoh E, Goto T, Ishihara Y. Effects of alkylphenols on bone metabolism in vivo and in vitro. Toxicol Lett. 2008;181(1):13–8.
Hermanussen M, Rol de Lama MA, Romero AP, Ruiz CA, Burmeister J, Tresguerres JA. Differential catch-up in body weight and bone growth after short-term starvation in rats. Growth Regul. 1996;6(4):230–7.
Hu P, Kennedy RC, Chen X, et al. Differential effects on adiposity and serum marker of bone formation by post-weaning exposure to methylparaben and butylparaben. Environ Sci Pollut Res Int. 2016;23(21):21957–68.
Hwang JK, Min KH, Choi KH, et al. Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts. Life Sci. 2013;93(9–11):367–72. https://doi.org/10.1016/J.LFS.2013.07.020.
Johnell O, Gullberg B, Kanis JA, et al. Risk factors for hip fracture in European women: the MEDOS study. J Bone Miner Res. 1995;10:1802–15.
Johnell O, Borgstrom F, Jonsson B, Kanis J. Latitude, socioeconomic prosperity, mobile phones and hip fracture risk. Osteoporos Int. 2007;18(3):333–7.
Kaludjerovic J, Ward WE. Diethylstilbesterol has gender-specific effects on weight gain and bone development in mice. J Toxicol Environ Heal Part A. 2008;71(15):1032–42. https://doi.org/10.1080/15287390801988947.
Kamei S, Miyawaki J, Sakayama K, Yamamoto H, Masuno H. Perinatal and postnatal exposure to 4-tert-octylphenol inhibits cortical bone growth in width at the diaphysis in female mice. Toxicology. 2008;252(1–3):99–104.
Kanno S, Hirano S, Kayama F. Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells. Toxicology. 2004;196(1–2):137–45. https://doi.org/10.1016/J.TOX.2003.12.002.
Karlamangla AS, Mori T, Merkin SS, et al. Childhood socioeconomic status and adult femoral neck bone strength: findings from the midlife in the United States study. Bone. 2013;56(2):320–6.
Khalil N, Ebert JR, Honda M, et al. Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8–12 year old children: a pilot study. Environ Res. 2018;160:314–21. https://doi.org/10.1016/j.envres.2017.10.014.
Khanna S, Darbre PD. Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells. J Appl Toxicol. 2013;33:378–82.
Kim JC, Shin HC, Cha SW, Koh WS, Chung MK, Han SS. Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy. Life Sci. 2001;69:2611. https://doi.org/10.1016/S0024-3205(01)01341-8.
Kim DH, Oh CH, Hwang Y-C, et al. Serum bisphenol A concentration in postmenopausal women with osteoporosis. J Bone Metab. 2012;19(2):87. https://doi.org/10.11005/JBM.2012.19.2.87.
Korkalainen M, Kallio E, Olkku A, et al. Dioxins interfere with differentiation of osteoblasts and osteoclasts. Bone. 2009;44(6):1134–42. https://doi.org/10.1016/J.BONE.2009.02.019.
Koskela A, Finnilä MA, Korkalainen M, et al. Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation. Toxicol Appl Pharmacol. 2016;301:14–21. https://doi.org/10.1016/j.taap.2016.04.002.
Lejonklou MH, Christiansen S, Örberg J, et al. Low-dose developmental exposure to bisphenol A alters the femoral bone geometry in wistar rats. Chemosphere. 2016;164:339–46. https://doi.org/10.1016/j.chemosphere.2016.08.114.
Li G, Xu Z, Hou L, et al. Differential effects of bisphenol A diglycidyl ether on bone quality and marrow adiposity in ovary-intact and ovariectomized rats. Am J Physiol Metab. 2016;311(6):E922–7. https://doi.org/10.1152/ajpendo.00267.2016.
Lind T, Lejonklou MH, Dunder L, et al. Low-dose developmental exposure to bisphenol A induces sex-specific effects in bone of Fischer 344 rat offspring. Environ Res. 2017;159:61–8.
Lind T, Lejonklou MH, Dunder L, et al. Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only. Environ Res. 2019;177:108584.
Liu C, Fuertes E, Flexeder C, et al. Associations between ambient air pollution and bone turnover markers in 10-year old children: results from the GINIplus and LISAplus studies. Int J Hyg Environ Health. 2015;218(1):58–65.
Lv QB, Gao X, Liu X, et al. The serum 25-hydroxyvitamin D levels and hip fracture risk: a meta-analysis of prospective cohort studies. Oncotarget. 2017;8(24):39849–58.
Marcus L, Menczel J. Higher prevalence of osteoporosis among female holocaust survivors. Osteoporos Int. 2007;18(11):1501–6.
McAnulty PA, Skydsgaard M. Diethylstilbestrol (DES): carcinogenic potential in Xpa −/−, Xpa −/− /p53 +/−, and wild-type mice during 9 months’ dietary exposure. Toxicol Pathol. 2005;33(5):609–20. https://doi.org/10.1080/01926230500261377.
Miki Y, Hata S, Nagasaki S, et al. Steroid and xenobiotic receptor-mediated effects of bisphenol A on human osteoblasts. Life Sci. 2016;155:29–35. https://doi.org/10.1016/j.lfs.2016.05.013.
Min K, Min J. Urinary phthalate metabolites and the risk of low bone mineral density and osteoporosis in older women. J Clin Endocrinol Metab. 2014;99(10):E1997–2003. https://doi.org/10.1210/jc.2014-2279.
Misra M, Klibanski A. Anorexia nervosa and bone. J Endocrinol. 2014;221(3):R163–76.
Odén A, Kanis JA, McCloskey EV, Johansson H. The effect of latitude on the risk and seasonal variation in hip fracture in Sweden. J Bone Miner Res. 2014;29(10):2217–23.
Paunescu A-C, Dewailly E, Dodin S, Nieboer E, Ayotte P. Dioxin-like compounds and bone quality in Cree women of eastern James Bay (Canada): a cross-sectional study. Environ Health. 2013;12(1):54. https://doi.org/10.1186/1476-069X-12-54.
Pelch KE, Carleton SM, Phillips CL, Nagel SC. Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice. Biol Reprod. 2012;86(3):69. https://doi.org/10.1095/biolreprod.111.096545.
Raecker T, Thiele B, Boehme RM, Guenther K. Endocrine disrupting nonyl- and octylphenol in infant food in Germany: considerable daily intake of nonylphenol for babies. Chemosphere. 2011;82(11):1533–40.
Rodríguez J, Mandalunis PM. Effect of cadmium on bone tissue in growing animals. Exp Toxicol Pathol. 2016;68(7):391–7.
Rowas S, Haddad R, Gawri R, et al. Effect of in utero exposure to diethylstilbestrol on lumbar and femoral bone, articular cartilage, and the intervertebral disc in male and female adult mice progeny with and without swimming exercise. Arthritis Res Ther. 2012;14(1):R17. https://doi.org/10.1186/ar3696.
Sabbieti MG, Agas D, Palermo F, et al. 4-nonylphenol triggers apoptosis and affects 17-β-estradiol receptors in calvarial osteoblasts. Toxicology. 2011;290(2–3):334–41.
Schutte R, Nawrot TS, Richart T, et al. Bone resorption and environmental exposure to cadmium in women: a population study. Environ Health Perspect. 2008;116(6):777–83.
Seidlová-Wuttke D, Jarry H, Wuttke W. Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol A (BPA) and dibutylphtalate (DBP) in uterus, vagina and bone. Toxicology. 2004;205(1–2):103–12. https://doi.org/10.1016/j.tox.2004.06.042.
Shi T, Min M, Ye P, et al. Meteorological variables and the risk of fractures: a systematic review and meta-analysis. Sci Total Environ. 2019;685:1030–41.
Sun N, Wang H, Ju Z, Zhao H. Effects of chronic cadmium exposure on metamorphosis, skeletal development, and thyroid endocrine disruption in Chinese toad Bufo gargarizans tadpoles. Environ Toxicol Chem. 2018;37(1):213–23.
Swift SN, Baek K, Swift JM, Bloomfield SA. Restriction of dietary energy intake has a greater impact on bone integrity than does restriction of calcium in exercising female rats. J Nutr. 2012;142(6):1038–45.
Talbott SM, Rothkopf MM, Shapses SA. Dietary restriction of energy and calcium alters bone turnover and density in younger and older female rats. J Nutr. 1998;128(3):640–5.
Tang X, Liu G, Kang J, et al. Obesity and risk of hip fracture in adults: a meta-analysis of prospective cohort studies. PLoS One. 2013;8:e55077.
Toda K, Miyaura C, Okada T, Shizuta Y. Dietary bisphenol A prevents ovarian degeneration and bone loss in female mice lacking the aromatase gene (Cyp 19 ). Eur J Biochem. 2002;269(8):2214–22. https://doi.org/10.1046/j.1432-1033.2002.02879.x.
Trivedi D, Doll R, Khaw KT. Effect of four monthly oral vitamin D (cholecalciferol) supplementation on fractures and mortality in men and women: randomised double blind controlled trial. BMJ. 2003;326:469–5.
Vitku J, Kolatorova L, Franekova L, et al. Endocrine disruptors of the bisphenol and paraben families and bone metabolism. Physiol Res. 2018;67:455–64.
Watson ATD, Nordberg RC, Loboa EG, Kullman SW. Evidence for aryl hydrocarbon receptor-mediated inhibition of osteoblast differentiation in human mesenchymal stem cells. Toxicol Sci. 2019;167(1):145–56. https://doi.org/10.1093/toxsci/kfy225.
Wu L, Wei Q, Lv Y, et al. Wnt/β-catenin pathway is involved in cadmium-induced inhibition of osteoblast differentiation of bone marrow mesenchymal stem cells. Int J Mol Sci. 2019;20(6):1519.
Zhao H, Bi Y, Ma L, et al. The effects of bisphenol A (BPA) exposure on fat mass and serum leptin concentrations have no impact on bone mineral densities in non-obese premenopausal women. Clin Biochem. 2012;45(18):1602–6.
Zhao H, Liu W, Wang Y, et al. Cadmium induces apoptosis in primary rat osteoblasts through caspase and mitogen-activated protein kinase pathways. J Vet Sci. 2015;16(3):297–306.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Springer Nature Switzerland AG
About this entry
Cite this entry
Grammatiki, M., Antonopoulou, V., Kotsa, K. (2023). Environmental Impact on Bone Health. In: Pivonello, R., Diamanti-Kandarakis, E. (eds) Environmental Endocrinology and Endocrine Disruptors . Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-030-39044-0_12
Download citation
DOI: https://doi.org/10.1007/978-3-030-39044-0_12
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-39043-3
Online ISBN: 978-3-030-39044-0
eBook Packages: MedicineReference Module Medicine