Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year

IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

See all formats and pricing
More options …
Volume 51, Issue 8 (Aug 2013)


Trace elements and bone health

Ivana Zofková / Petra Nemcikova
  • Department of Internal Medicine, Hospital of Jindrichuv Hradec, Jindrichuv Hradec, Czech Republic
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Petr Matucha
Published Online: 2013-03-18 | DOI: https://doi.org/10.1515/cclm-2012-0868


The importance of nutrition factors such as calcium, vitamin D and vitamin K for the integrity of the skeleton is well known. Moreover, bone health is positively influenced by certain elements (e.g., zinc, copper, fluorine, manganese, magnesium, iron and boron). Deficiency of these elements slows down the increase of bone mass in childhood and/or in adolescence and accelerates bone loss after menopause or in old age. Deterioration of bone quality increases the risk of fractures. Monitoring of homeostasis of the trace elements together with the measurement of bone density and biochemical markers of bone metabolism should be used to identify and treat patients at risk of non-traumatic fractures. Factors determining the effectivity of supplementation include dose, duration of treatment, serum concentrations, as well as interactions among individual elements. Here, we review the effect of the most important trace elements on the skeleton and evaluate their clinical importance.

Keywords: bone density; bone quality; cadmium; copper; magnesium; manganese; zinc


  • 1.

    Lowe NM, Fraser WD, Jackson MJ. Micronutrient Group Symposium on Micronutrient Supplementation: is there a case? Is there a potential therapeutic value of copper and zinc for osteoporosis? Proc Nutr Soc 2002;61:181–5.CrossrefGoogle Scholar

  • 2.

    Ryz NR, Weiler HA, Tailor CG. Zinc deficiency reduces bone mineral density in the spine of young adult rats: a pilot study. Ann Nutr Metab 2009;54:218–26.CrossrefPubMedGoogle Scholar

  • 3.

    Headley KB, Newman SM, Hunt JR. Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats. J Nutr Biochem 2010;21:297–303.CrossrefGoogle Scholar

  • 4.

    Hill T, Meunier N, Andriollo-Sanchez M, Ciarapica D, Hininger-Favier I, Polito A, et al. The relationship between the zinc nutritive status and biochemical markers of bone turnover in older European adults: the ZENITH study. Eur J Clin Nutr 2005;59(Suppl 2):S73–8.Google Scholar

  • 5.

    Saltman PD, Strause LG. The role of trace minerals in osteoporosis. J Am Coll Nutr 1993;12:384–9.PubMedCrossrefGoogle Scholar

  • 6.

    Atik OS, Uslu MM, Eksioglu F, Satana T. Etiology of senile osteoporosis. A hypothesis. Clin Orthopaed Related Res 2006;443:25–7.Google Scholar

  • 7.

    Strause L, Saltman P, Smyth KT, Bracker M, Andon MB. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 1994;124:1060–4.PubMedGoogle Scholar

  • 8.

    Yamaguchi M, Uchiyama S, Ishiyama K, Hashimoto K. Oral administration in combination with zinc enhances β-cryptoxanthin-induced anabolic effects on bone components in the femoral tissues of rats in vivo. Biol Pharm Bull 2006;29:371–4.CrossrefGoogle Scholar

  • 9.

    Gonzalez-Reimers E, Duran-Castellon MC, Martin-Olivera R, Polez-Lirola S, Santolaria-Fernandez F, Della Vega-Prieto MJ, et al. Effects of zinc supplementation on ethanol-mediated bone alterations. Food Chem Toxicol 2005;43:1497–505.CrossrefGoogle Scholar

  • 10.

    Jamieson JA, Tailor CG, Weiler HA. Marginal zinc deficiency exacerbates bone lead accumulation and high dietary zinc attenuates lead accumulation at the expense of bone density in growing rats. Toxicol Sci 2006;92:286–94.CrossrefPubMedGoogle Scholar

  • 11.

    Brzóska MM, Rogalska J, Galazyn-Sidorczuk M, Jurczuk M, Roszczenko A, Kulikowska-Karpińska E, et al. Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology 2007;237:89–103.Google Scholar

  • 12.

    Suzuki Y, Merita I, Yamane Y, Murota S. Preventive effects of zinc on cadmium-induced inhibition of alkaline phosphatase activity and mineralization activity in osteoblast-like cells, MC3T3-E1. J Pharmacobiodyn 1989;12:94–9.CrossrefGoogle Scholar

  • 13.

    Kalinowski J, Chavez ER. Tissue composition and trace mineral content of the dam and litter under low dietary zinc intake during gestation and lactation of first-litter gilts. J Trace Elem Electrolytes Health Dis 1991;5:35–46.Google Scholar

  • 14.

    Bolze MS, Reeves RD, Lindbeck FE, Elders MJ. Influence of zinc on growth, somatomedin, and glycosaminoglycan metabolism in rats. Am J Physiol 1987;252:421–6Google Scholar

  • 15.

    Meunier N, O’Connor JM, Maiani G, Cashman KD, Secker DL, Ferry M, et al. Importance of zinc in the elderly: the ZENITH study. Eur J Clin Nutr 2005;59(Suppl 2):S1–4.Google Scholar

  • 16.

    Hosea HJ, Taylor CG, Wood T, Mollard R, Weiler HA. Zinc-deficient rats have more limited bone recovery during repletion than diet-restricted rats. Exp Biol Med (Maywood) 2004;229:303–11.Google Scholar

  • 17.

    Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 2006;20:3–18.CrossrefPubMedGoogle Scholar

  • 18.

    Palacios C. The role of nutrients in bone health, from A to Z. Crit Rev Food Sci Nutr 2006;46:621–8.CrossrefGoogle Scholar

  • 19.

    Harris ED, Rayton JK, Balthrop JE, Di Silvestro RA, Garcia-de-Quevedo M. Copper and the synthesis of elastin and collagen. Ciba Found Symp 1980;79:163–82.Google Scholar

  • 20.

    Rucker RB, Kosinem T, Clegg MS, Mitechell AE, Rucker BR, Uriu-Hare JY, et al. Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr 1998;67: 996S–1002S.Google Scholar

  • 21.

    Kubiak K, Klimczak A, Dziki L, Modranka R, Malinowska K. Influence of copper (II) complex on the activity of selected oxidative enzymes. Pol Merkur Lakarski 2010;28:22–5.Google Scholar

  • 22.

    Li BB, Yu SF. In vitro study of the effects of copper ion on osteoclastic resorption in various dental mineralized tissues. Zhoghua Kou Qiang Yi Xue Za Zhi 2007;42:110–3.Google Scholar

  • 23.

    Marquardt ML, Done SL, Sandrock M, Bermon WE, Feldman KW. Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants. Pediatrics 2012;130:e695–8.CrossrefGoogle Scholar

  • 24.

    Mutlu M, Argun N, Kilic E, Saraymen R, Yazar S. Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. J Int Med Res 2007;35:692–5.CrossrefPubMedGoogle Scholar

  • 25.

    Price CT, Langfordt JR, Liporace FA. Essential nutrients for bone health and a review of their availability in the average North American diet. Open Orthop J 2012;6:143–9.PubMedGoogle Scholar

  • 26.

    Aina V, Lusvardi G, Annaz B, Gibbon IR, Imrie FE, Malavasi G, et al. Magnesium- and stroncium-co-substituted hydroxyapatite: the effects of doped-ions on the structure and chemico-physical properties. J Mater Sci Mater Med 2012;23:2867–79.CrossrefGoogle Scholar

  • 27.

    Kanazawa I, Yamamoto M, Yamaguchi T, Yano S, Sugimoto T. A case of magnesium deficiency associated with insufficient parathyroid hormone action and severe osteoporosis. Endocr J 2007;54:935–40.CrossrefPubMedGoogle Scholar

  • 28.

    Rude RK, Singer FR, Gruber HE. Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr 2009;28:131–41.PubMedCrossrefGoogle Scholar

  • 29.

    Matias CN, Santos DA, Monteiro CP, Vasco AM, Baptista F, Sardinha LB, et al. Magnesium intake mediates the association between bone mineral density and lean soft tissue in elite swimmers. Magnes Res 2012;25:120–5.PubMedGoogle Scholar

  • 30.

    Kim MH, Yeon JY, Choi MK, Bae YJ. Evaluation of magnesium intake and its relation with bone quality in healthy young women. Biol Trace Elem Res 2011;144:109–17.CrossrefPubMedGoogle Scholar

  • 31.

    New SA, Robins SP, Campbell MK, Martin JC, Garton MJ, Bolton-Smith C, et al. Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr 2000;71:142–51.Google Scholar

  • 32.

    Saito N, Tabata N, Saito S, Andou Y, Onaga Y, Iwamitsu A, et al. Bone mineral density, serum albumin and serum magnesium. J Am Coll Nutr 2004;23:701S–3S.CrossrefGoogle Scholar

  • 33.

    Nieves JW. Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D. Osteoporos Int 2013;24:771–86.CrossrefPubMedGoogle Scholar

  • 34.

    Meyer TE, Verwoert GC, Hwang SJ, Glazer NL, Smith AV, van Rooij FJ, et al. Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six loci influencing serum magnesium levels. PLoS Genet 2010;6:e1001–45.Google Scholar

  • 35.

    Madeiros DM, Stoecker B, Plattner A, Jennings D, Haub M. Iron deficiency negatively affects vertebrae and femurs of rats independently of energy intake and body weight. J Nutr 2004;134:3061–7.Google Scholar

  • 36.

    Parelman M, Stoecker B, Baker A, Medeiros D. Iron restriction negatively affects bone in female rats and mineralization of hFOB osteoblast cells. Exp Biol Med (Maywood) 2006;231:378–86.Google Scholar

  • 37.

    Diaz-Castro J, López-Frias MR, Campos MS, López-Frias M, Alférez MJ, Nestares T, et al. Severe nutritional iron-deficiency anaemia has a negative effect on some bone turnover biomarkers in rats. Eur J Nutr 2012;51:241–7.CrossrefGoogle Scholar

  • 38.

    Diaz-Castro J, Ramírez López-Frias M, Campos MS, López-Frias M, Alférez MJ, Nestares T, et al. Goat milk during iron repletion improves bone turnover impaired by severe iron deficiency. J Dairy Sci 2011;94:2752–61.CrossrefGoogle Scholar

  • 39.

    Guggenbuhl P, Deugnier Y, Boisdet JF, Rolland Y, Perdriger A, Pawlotsky Y, et al. Bone mineral density in men with genetic hemochromatosis and HFGE gene mutation. Osteoporosis Int 2005;16:1809–14.CrossrefGoogle Scholar

  • 40.

    Clegg MS, Donovan SM, Monaco MH, Baly DL, Ensunsa JL, Keen CL. The influence of manganese deficiency on serum IGF-1 and IGF binding proteins in the male rat. Proc Soc Exp Biol Med 1998;219:41–7.Google Scholar

  • 41.

    Itokawa Y. Trace elements in long-term total parenteral nutrition. Nihon Rinsho 1996;54:172–8.PubMedGoogle Scholar

  • 42.

    Rico H, Gómez-Raso N, Sevilla M, Hernándfez ER, Seco C, Páez E, et al. Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitometric study. Eur J Obstet Gynecol Reprod Biol 2000;90:97–101.CrossrefGoogle Scholar

  • 43.

    Rahnama M, Bloniarz J, Zareba S, Swiatkowski W. Study of estrogen deficiency impact on manganese levels in teeth and mandible of rats after ovariectomy. Rocz Panstw Zakl Hig 2003;54:33–8.Google Scholar

  • 44.

    Nemcikova P, Spevackova V, Cejchanova M, Hill M, Zofkova I. Relationship of serum manganese and copper levels to bone density and quality in postmenopausal women. A pilot study. Osteol Bull 2009;14:97–100.Google Scholar

  • 45.

    Devirian TA, Volpe SL. The physiological effects of dietary boron. Crit Rev Food Sci Nutr 2003;43:219–31.CrossrefPubMedGoogle Scholar

  • 46.

    Hunt CD. Dietary boron: progress in establishing essentials roles in human physiology. J Trace Elem Med Biol 2012;26:2–3.CrossrefGoogle Scholar

  • 47.

    Nielsen FH, Stoecker BJ. Boron and fish oil have different beneficial effects on strength and trabecular microarchitecture of bone. J Trace Elem Med Biol 2009;23:195–203.PubMedCrossrefGoogle Scholar

  • 48.

    Cao JJ, Gregoire BR, Zeng H. Selenium deficiency decreases antioxidative capacity and is detrimental to bone microarchitecture in mice. J Nutr 2012;142:1526–31.Google Scholar

  • 49.

    Moreno-Reyes R, Egrise D, Neve 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;16:1556–63.CrossrefGoogle Scholar

  • 50.

    Hoeg A, Gogakos A, Mureny E, Mueller S, Köhrle J, Reid DM, et al. Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women. Clin Endocrinol Metab 2012;97:4061–70.CrossrefGoogle Scholar

  • 51.

    Arikan DC, Coskun A, Ozer A, Kilinc M, Atalay F, Arikan T. Plasma selenium, zinc, copper and lipid levels in postmenopausal Turkish women and their relation with osteoporosis. Biol Trace Elem Res 2011;144:407–17.CrossrefPubMedGoogle Scholar

  • 52.

    Turner CH, Garetto LP, Dunipace AJ, Zhang W, Wilson ME, Grynpas MD, et al. Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif Tissue Int 1997;61:77–83.CrossrefGoogle Scholar

  • 53.

    Khandare AL, Suresh P, Kumar PU, Laksmaiah N, Manula N, Rao GS. Beneficial effect of copper supplementation on deposition of fluoride in bone in fluoride- and molybdenum-fed rabbits. Calcif Tissue Int 2005;77:233–8.PubMedCrossrefGoogle Scholar

  • 54.

    Ohba K, Okawa Y, Matsumoto Y, Nakamura Y, Ohta H. A study of investigation of cadmium genotoxicity in rat bone cells using DNA microarray. J Toxicol Sci 2007;32:107–9.PubMedCrossrefGoogle Scholar

  • 55.

    Kazantzis G. Cadmium, osteoporosis and calcium metabolism. Biometals mechanical, biochemical, and histopathological evaluation. Ecotoxicol Environ Saf 2007;66:267–71.Google Scholar

  • 56.

    Akesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, et al. Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 2006;114:830–4.CrossrefGoogle Scholar

  • 57.

    Comelekoglu U, Yalin S, Bagis S, Ogenler O, Sahin NO, Yildiz A, et al. Low-exposure cadmium is more toxic on osteoporotic rat femoral bone: mechanical, biochemical, and histopathological evaluation. Ecotoxicol Environ Saf 2007;66:267–71.PubMedCrossrefGoogle Scholar

  • 58.

    Sakai T, Wariishi M, Nishiyama K. Changes in trace element concentrations in hair of growing children. Biol Trace Elem Res 2000;77:43–51.PubMedCrossrefGoogle Scholar

About the article

Ivana Zofková

Prof. Ivana Žofková, MD, PhD, DSc. is involved in the study of sample enlargement, postmenopausal osteoporosis treatment and in results analysis. Medicine, Charles University, Prague, graduated in 1966. Postgradual experiences and main fields of interest: PhD Thesis – Humoral factors in the pathogenesis of arterial hypertension, Charles University, Prague, 1975. Doctor of Science (DSc.)– The influence of calcium and calciotropic drugs on humoral regulations, Charles University, Prague, 1992. Associate Professor of Internal Medicine – The pathogenesis of osteoporosis, 3rd Faculty of Medicine, Charles University, Prague, 1996. Professor of Internal Medicine – Sex steroids and the skeleton, 3rd Faculty of Medicine, Charles University, Prague, 2003. Research into genetics of osteoporosis, 2003 until now. Clinical praxis – Department of Internal Medicine, Charles University Hospitals in Pilsen and in Prague, Department of Clinical Endocrinology in the Institute of Endocrinology.

Petra Nemcikova

Petra Nemcikova, MD, graduated from Charles University, Prague in 2010. After graduation she started to work in the District Hospital of Internal Medicine, Jindrichuv Hradec. Now she is a PhD student of Professor Zofkova, Institute of Endocrinology, Prague. Her PhD thesis is: Trace elements and calcium-phosphate metabolism.

Petr Matucha

Petr Matucha, MSc. Highest achieved education: Faculty of Sciences, Charles University, 1986–91, analytical chemistry. Clinical, educational and professional activity: 1992–1997 in Institute of Endocrinology Prague; 1996–97 as biochemist in Institute of Inherited Metabolic Disorders, General Faculty Hospital Prague; 1997 to present as scientist in the Institute of Endocrinology Prague, Department of Clinical Immunoendocrinology.

Corresponding author: Prof. MUDr. Ivana Zofková, DrSc., Institute of Endocrinology, Narodni 8, 116 94 Prague 1, Czech Republic

Received: 2012-12-11

Accepted: 2013-02-07

Published Online: 2013-03-18

Published in Print: 2013-08-01

Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0868.

Export Citation

©2013 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Christina L. Brunnquell, Reinier Hernandez, Stephen A. Graves, Ivy Smit-Oistad, Robert J. Nickles, Weibo Cai, M. Elizabeth Meyerand, and Masatoshi Suzuki
Contrast Media & Molecular Imaging, 2016, Volume 11, Number 5, Page 371
Xiaoman Luo, Davide Barbieri, Noel Davison, Yonggang Yan, Joost D. de Bruijn, and Huipin Yuan
Acta Biomaterialia, 2014, Volume 10, Number 1, Page 477
Binxiu Zhao, Kunzheng Wang, Jiexiu Zhao, and Yufeng Luo
Biological Trace Element Research, 2013, Volume 154, Number 3, Page 333

Comments (0)

Please log in or register to comment.
Log in