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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Mini-Review Article

Selenium: A Trace Element for a Healthy Skeleton - A Narrative Review

Author(s): Fabio Vescini, Iacopo Chiodini, Andrea Palermo, Roberto Cesareo, Vincenzo De Geronimo, ">Alfredo Scillitani, Luigi Gennari and Alberto Falchetti*

Volume 21, Issue 4, 2021

Published on: 27 June, 2020

Page: [577 - 585] Pages: 9

DOI: 10.2174/1871530320666200628030913

Price: $65


Inadequate serum selenium levels may delay the growth and physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an antioxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and selenium-proteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric sites. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism.

Keywords: Selenium, bone metabolism, bone turnover, osteoclasts, anti-oxidation activity, inflammation.

Graphical Abstract
Epidemiology for Public Health. Available at:. http://www.epicentro.iss. it/problemi/sali/oligoelementi.asp
Recommendations, N.N. 2012 Working Group. Nordic Nutrition Recommendations 2012, 5th Ed; Nordic Council of Ministers: Copenhagen, Denmark, 2014, p. 128.
Joint Food and Agriculture Organization/World Health Organization Expert Consultation on Human Vitamin and Mineral Requirements. Vitamin and Mineral Requirements in Human Nutrition, 2nd Ed; World Health Organization and Food and Agriculture Organization of the United Nations: Geneva, Switzerland, 2004, pp. 194-210.
Jones, G.D.; Droz, B.; Greve, P.; Gottschalk, P.; Poffet, D.; McGrath, S.P.; Seneviratne, S.I.; Smith, P.; Winkel, L.H. Selenium deficiency risk predicted to increase under future climate change. Proc. Natl. Acad. Sci. USA, 2017, 114(11), 2848-2853.
[] [PMID: 28223487]
Fordyce Fordyce, F.M. Selenium deficiency and toxicity in the environment. Essentials of Medical Geology; Selinus, O.; Alloway, B.; Centeno, J.A.; Finkelman, R.B.; Fuge, R.; Lindh, U; Smedley, P., Ed.; Elsevier: London, 2005, pp. 373-415.
European Food Safety Authority (EFSA), The Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for selenium. EFSA J., 2014, 12, 1-67.
Dickson, R.C.; Tomlinson, R.H. Selenium in blood and human tissues. Clin. Chim. Acta, 1967, 16(2), 311-321.
[] [PMID: 4166400]
Beckett, G.J.; Arthur, J.R. Selenium and endocrine systems. J. Endocrinol., 2005, 184(3), 455-465.
[] [PMID: 15749805]
Jablonska, E.; Vinceti, M. Selenium and Human Health: Witnessing a Copernican Revolution? J. Environ. Sci. Health C. Environ. Carcinog. Ecotoxicol. Rev., 2015, 33(3), 328-368.
[] [PMID: 26074278]
Rayman, M.P.; Winther, K.H.; Pastor-Barriuso, R.; Cold, F.; Thvilum, M.; Stranges, S.; Guallar, E.; Cold, S. Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radic. Biol. Med., 2018, 127, 46-54.
[] [PMID: 29454039]
Fazzalari, N.L. Bone remodeling: a review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip. Semin. Cell Dev. Biol., 2008, 19(5), 467-472.
[] [PMID: 18771742]
Vescini, F.; Attanasio, R.; Balestrieri, A.; Bandeira, F.; Bonadonna, S.; Camozzi, V.; Cassibba, S.; Cesareo, R.; Chiodini, I.; Francucci, C.M.; Gianotti, L.; Grimaldi, F.; Guglielmi, R.; Madeo, B.; Marcocci, C.; Palermo, A.; Scillitani, A.; Vignali, E.; Rochira, V.; Zini, M. Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis. J. Endocrinol. Invest., 2016, 39(7), 807-834.
[] [PMID: 26969462]
Zeng, H.; Cao, J.J.; Combs, Jr., G.F. Selenium in bone health: roles in antioxidant protection and cell proliferation. Nutrients, 2013, 5(1), 97-110.
[] [PMID: 23306191]
Langdahl, B.; Ferrari, S.; Dempster, D.W. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther. Adv. Musculoskelet. Dis., 2016, 8(6), 225-235.
[] [PMID: 28255336]
Tian, A.; Ma, J.; Feng, K.; Liu, Z.; Chen, L.; Jia, H.; Ma, X. Reference markers of bone turnover for prediction of fracture: a meta-analysis. J. Orthop. Surg. Res., 2019, 14(1), 68.
[] [PMID: 30819222]
Morris, H.A.; Eastell, R.; Jorgensen, N.R.; Cavalier, E.; Vasikaran, S.; Chubb, S.A.P.; Kanis, J.A.; Cooper, C.; Makris, K. IFCC-IOF working group for standardisation of bone marker assays (WG-BMA). Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin. Chim. Acta, 2017, 467, 34-41.
[] [PMID: 27374301]
Parfitt, A.M. What is the normal rate of bone remodeling? Bone, 2004, 35(1), 1-3.
[] [PMID: 15207734]
Parfitt, A.M.; Mundy, G.R.; Roodman, G.D.; Hughes, D.E.; Boyce, B.F. A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J. Bone Miner. Res., 1996, 11(2), 150-159.
[] [PMID: 8822338]
Ebert, R.; Ulmer, M.; Zeck, S.; Meissner-Weigl, J.; Schneider, D.; Stopper, H.; Schupp, N.; Kassem, M.; Jakob, F. Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro. Stem Cells, 2006, 24(5), 1226-1235.
Duntas, L.H. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm. Metab. Res., 2009, 41(6), 443-447.
[] [PMID: 19418416]
Mehta, S.L.; Kumari, S.; Mendelev, N.; Li, P.A. Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci., 2012, 13, 79.
[] [PMID: 22776356]
Cosso, R.; Falchetti, A. Mitochondriopathies and bone health. J. Tre. Bio. Res., 2018, 1(1), 1-7.
Moreno-Reyes, R.; Egrise, D.; Nève, J.; Pasteels, J.L.; Schoutens, A. Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia. J. Bone Miner. Res., 2001, 16(8), 1556-1563.
[] [PMID: 11499879]
Cao, J.J.; Gregoire, B.R.; Zeng, H. Selenium deficiency decreases antioxidative capacity and is detrimental to bone microarchitecture in mice. J. Nutr., 2012, 142(8), 1526-1531.
[] [PMID: 22739365]
Hoeg, A.; Gogakos, A.; Murphy, E.; Mueller, S.; Köhrle, J.; Reid, D.M.; Glüer, C.C.; Felsenberg, D.; Roux, C.; Eastell, R.; Schomburg, L.; Williams, G.R. Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women. J. Clin. Endocrinol. Metab., 2012, 97(11), 4061-4070.
[] [PMID: 22904175]
Dreher, I.; Schütze, N.; Baur, A.; Hesse, K.; Schneider, D.; Köhrle, J.; Jakob, F. Selenoproteins are expressed in fetal human osteoblast-like cells. Biochem. Biophys. Res. Commun., 1998, 245(1), 101-107.
[] [PMID: 9535791]
Jakob, F.; Becker, K.; Paar, E.; Ebert-Duemig, R.; Schütze, N. Expression and regulation of thioredoxin reductases and other selenoproteins in bone. Methods Enzymol., 2002, 347, 168-179.
[] [PMID: 11898403]
Köhrle, J.; Jakob, F.; Contempré, B.; Dumont, J.E. Selenium, the thyroid, and the endocrine system. Endocr. Rev., 2005, 26(7), 944-984.
[] [PMID: 16174820]
Xu, Z.S.; Wang, X.Y.; Xiao, D.M.; Hu, L.F.; Lu, M.; Wu, Z.Y.; Bian, J.S. Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage-implications for the treatment of osteoporosis. Free Radic. Biol. Med., 2011, 50(10), 1314-1323.
[] [PMID: 21354302]
Liu, H.; Bian, W.; Liu, S.; Huang, K. Selenium protects bone marrow stromal cells against hydrogen peroxide-induced inhibition of osteoblastic differentiation by suppressing oxidative stress and ERK signaling pathway. Biol. Trace Elem. Res., 2012, 150(1-3), 441-450.
[] [PMID: 22890880]
Pietschmann, N.; Rijntjes, E.; Hoeg, A.; Stoedter, M.; Schweizer, U.; Seemann, P.; Schomburg, L.P. Selenoprotein P is the essential selenium transporter for bones. Metallomics, 2014, 6(5), 1043-1049.
[] [PMID: 24626785]
Kim, H.; Lee, K.; Kim, J.M.; Kim, J-R.; Lee, H-W.; Chung, Y.W.; Shin, H-I.; Park, E-S.; Rho, J.; Lee, S.H.; Kim, N.; Lee, S.Y.; Choi, Y.; Jeong, D. Gradual repression of selenoprotein W ensures physiological bone remodeling. bioRxiv, 2018.
Ren, F.L.; Guo, X.; Zhang, R.J.; Wang, ShJ.; Zuo, H.; Zhang, Z.T.; Geng, D.; Yu, Y.; Su, M. Effects of selenium and iodine deficiency on bone, cartilage growth plate and chondrocyte differentiation in two generations of rats. Osteoarthritis Cartilage, 2007, 15(10), 1171-1177.
[] [PMID: 17490897]
Downey, C.M.; Horton, C.R.; Carlson, B.A.; Parsons, T.E.; Hatfield, D.L.; Hallgrímsson, B.; Jirik, F.R. Osteo-chondroprogenitor-specific deletion of the selenocysteine tRNA gene, Trsp, leads to chondronecrosis and abnormal skeletal development: a putative model for Kashin-Beck disease. PLoS Genet., 2009, 5(8)e1000616
[] [PMID: 19696890]
Mlakar, S.J.; Osredkar, J.; Prezelj, J.; Marc, J. Opposite effects of GSTM1--and GSTT1: gene deletion variants on bone mineral density. Dis. Markers, 2011, 31(5), 279-287.
[] [PMID: 22048269]
Jurkovic Mlakar, S.; Prezelj, J.; Osredkar, J.; Marc, J. BMD values and GSTM3 gene polymorphisms in combination with GSTT1/GSTM1 genes: a genetic association study in Slovenian elderly. Gerontology, 2012, 58(3), 238-248.
[] [PMID: 22327174]
Mlakar, S.J.; Prezelj, J.; Marc, J. Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process. Maturitas, 2012, 71(2), 180-187.
[] [PMID: 22221655]
Allen, J.R.; Humphries, I.R.; Waters, D.L.; Roberts, D.C.; Lipson, A.H.; Howman-Giles, R.G.; Gaskin, K.J. Decreased bone mineral density in children with phenylketonuria. Am. J. Clin. Nutr., 1994, 59(2), 419-422.
[] [PMID: 8310995]
Zeman, J.; Bayer, M.; Stepán, J. Bone mineral density in patients with phenylketonuria. Acta Paediatr., 1999, 88(12), 1348-1351.
[] [PMID: 10626520]
Wu, J.; Xu, G.L. Plasma selenium content, platelet glutathione peroxidase and superoxide dismutase activity of residents in Kashin-Beck disease affected area in China. J. Trace Elem. Electrolytes Health Dis., 1987, 1(1), 39-43.
[PMID: 2856563]
Zhang, J.; Munger, R.G.; West, N.A.; Cutler, D.R.; Wengreen, H.J.; Corcoran, C.D. Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am. J. Epidemiol., 2006, 163(1), 9-17.
[] [PMID: 16306312]
Wang, L.; Yu, H.; Yang, G.; Zhang, Y.; Wang, W.; Su, T.; Ma, W.; Yang, F.; Chen, L.; He, L.; Ma, Y.; Zhang, Y. Correlation between bone mineral density and serum trace element contents of elderly males in Beijing urban area. Int. J. Clin. Exp. Med., 2015, 8(10), 19250-19257.
[PMID: 26770561]
Wang, Y.; Xie, D.; Li, J.; Long, H.; Wu, J.; Wu, Z.; He, H.; Wang, H.; Yang, T.; Wang, Y. Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study. BMC Musculoskelet. Disord., 2019, 20(1), 585.
[] [PMID: 31801509]
Rayman, M.P. Food-chain selenium and human health: emphasis on intake. Br. J. Nutr., 2008, 100(2), 254-268.
[] [PMID: 18346308]
Beukhof, C.M.; Medici, M.; van den Beld, A.W.; Hollenbach, B.; Hoeg, A.; Visser, W.E.; de Herder, W.W.; Visser, T.J.; Schomburg, L.; Peeters, R.P. Selenium status is positively associated with bone mineral density in healthy aging European men. PLoS One, 2016, 11(4)e0152748
[] [PMID: 27055238]
Combs, G.F., Jr; Watts, J.C.; Jackson, M.I.; Johnson, L.K.; Zeng, H.; Scheett, A.J.; Uthus, E.O.; Schomburg, L.; Hoeg, A.; Hoefig, C.S.; Davis, C.D.; Milner, J.A. Determinants of selenium status in healthy adults. Nutr. J., 2011, 10, 75.
[] [PMID: 21767397]
Hoeflich, J.; Hollenbach, B.; Behrends, T.; Hoeg, A.; Stosnach, H.; Schomburg, L. The choice of biomarkers determines the selenium status in young German vegans and vegetarians. Br. J. Nutr., 2010, 104(11), 1601-1604.
[] [PMID: 20637135]
Ma, S.; Hill, K.E.; Caprioli, R.M.; Burk, R.F. Mass spectrometric characterization of full-length rat selenoprotein P and three isoforms shortened at the C terminus. Evidence that three UGA codons in the mRNA open reading frame have alternative functions of specifying selenocysteine insertion or translation termination. J. Biol. Chem., 2002, 277(15), 12749-12754.
[] [PMID: 11821412]
Cosso, R.; Falchetti, A. Vitamin K and bone metabolism: the myth and the truth. Expert Rev. Precis. Med. Drug Dev., 2016, 1(3), 301-317.
Falchetti, A.; Cosso, R. The interaction between vitamin C and bone health: a narrative review. Expert Rev. Precis. Med. Drug Dev., 2018, 3(3), 215-223.
Wolf, R.L.; Cauley, J.A.; Pettinger, M.; Jackson, R.; Lacroix, A.; Leboff, M.S.; Lewis, C.E.; Nevitt, M.C.; Simon, J.A.; Stone, K.L.; Wactawski-Wende, J. Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am. J. Clin. Nutr., 2005, 82(3), 581-588.
[] [PMID: 16155271]
Melhus, H.; Michaëlsson, K.; Holmberg, L.; Wolk, A.; Ljunghall, S. Smoking, antioxidant vitamins, and the risk of hip fracture. J. Bone Miner. Res., 1999, 14(1), 129-135.
[] [PMID: 9893075]
Bédard, A.; Northstone, K.; Holloway, J.W.; Henderson, A.J.; Shaheen, S.O. Maternal dietary antioxidant intake in pregnancy and childhood respiratory and atopic outcomes: birth cohort study. Eur. Respir. J., 2018, 52(2)1800507
[] [PMID: 30093569]
van Woudenbergh, G.J.; van Ballegooijen, A.J.; Kuijsten, A.; Sijbrands, E.J.; van Rooij, F.J.; Geleijnse, J.M.; Hofman, A.; Witteman, J.C.; Feskens, E.J. Eating fish and risk of type 2 diabetes: A population-based, prospective follow-up study. Diabetes Care, 2009, 32(11), 2021-2026.
[] [PMID: 19675200]
Rayman, M.P. Selenium and human health. Lancet, 2012, 379(9822), 1256-1268.
[] [PMID: 22381456]
Tonelli, M.; Wiebe, N.; Hemmelgarn, B.; Klarenbach, S.; Field, C.; Manns, B.; Thadhani, R.; Gill, J. Alberta kidney disease network. Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med., 2009, 7, 25.
[] [PMID: 19454005]
Stone, C.A.; Kawai, K.; Kupka, R.; Fawzi, W.W. Role of selenium in HIV infection. Nutr. Rev., 2010, 68(11), 671-681.
[] [PMID: 20961297]
Drake, E.N. Cancer chemoprevention: selenium as a prooxidant, not an antioxidant. Med. Hypotheses, 2006, 67(2), 318-322.
[] [PMID: 16574336]
Fairweather-Tait, S.J.; Bao, Y.; Broadley, M.R.; Collings, R.; Ford, D.; Hesketh, J.E.; Hurst, R. Selenium in human health and disease. Antioxid. Redox Signal., 2011, 14(7), 1337-1383.
[] [PMID: 20812787]
World Health Organization. Selenium. A Report of the International Programme on Chemical Safety. Environmental Health Criteria no. 58; WHO: Geneva, 1987.

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