Skip to main content

Advertisement

SpringerLink
Log in

Low Serum Levels of Zinc, Copper, and Iron as Risk Factors for Osteoporosis: a Meta-analysis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the growth, development, and maintenance of healthy bones. However, there are conflicting reports as to the relationship between serum level of Zn, Cu, or Fe and osteoporosis (OP). The purpose of the present study is to clarify the relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach. We searched all articles indexed in PubMed published up to May 2014 concerning the association between serum level of Zn, Cu, or Fe and OP. Eight eligible articles involving 2,188 subjects were identified. Overall, pooled analysis indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the healthy controls (Zn standardized mean difference (SMD) = −1.396, 95 % confidence interval (CI) = [−2.129, −0.663]; Cu SMD = −0.386, 95 % CI = [−0.538, −0.234]; Fe SMD = −0.22, 95 % CI = [−0.30, −0.13]). Further subgroup analysis found that geographical location and gender had an influence on the serum level of Zn in OP and healthy controls, but not on the serum level of Cu or Fe. No evidence of publication bias was observed. In conclusion, this meta-analysis suggests that low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and well-designed studies with adequate control for confounding factors are required in future investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zofkova I, Nemcikova P, Matucha P (2013) Trace elements and bone health. Clin Chem Lab Med 51:1555–1561

    CAS  PubMed  Google Scholar 

  2. Zheng J, Mao X, Ling J, He Q, Quan J et al (2014) Association between serum level of magnesium and postmenopausal osteoporosis: a meta-analysis. Biol Trace Elem Res. doi:10.1007/s12011-014-9961-3

    Google Scholar 

  3. Wynchank S, Saltman PD (1997) Trace elements and osteoporosis. S Afr Med J 87:473–474

    CAS  PubMed  Google Scholar 

  4. Davey DA (1997) Trace elements and osteoporosis. S Afr Med J 87:902

    CAS  PubMed  Google Scholar 

  5. Hsieh HS, Navia JM (1980) Zinc deficiency and bone formation in guinea pig alveolar implants. J Nutr 110:1581–1588

    CAS  PubMed  Google Scholar 

  6. Burch RE, Hahn HK, Sullivan JF (1975) Newer aspects of the roles of zinc, manganese, and copper in human nutrition. Clin Chem 21:501–520

    CAS  PubMed  Google Scholar 

  7. Nagata M, Kayanoma M, Takahashi T, Kaneko T, Hara H (2011) Marginal zinc deficiency in pregnant rats impairs bone matrix formation and bone mineralization in their neonates. Biol Trace Elem Res 142:190–199

    Article  CAS  PubMed  Google Scholar 

  8. Yamaguchi M, Goto M, Uchiyama S, Nakagawa T (2008) Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions. Mol Cell Biochem 312:157–166

    Article  CAS  PubMed  Google Scholar 

  9. Hie M, Iitsuka N, Otsuka T, Nakanishi A, Tsukamoto I (2011) Zinc deficiency decreases osteoblasts and osteoclasts associated with the reduced expression of Runx2 and RANK. Bone 49:1152–1159

    Article  CAS  PubMed  Google Scholar 

  10. Yamaguchi M, Segawa Y, Shimokawa N, Tsuzuike N, Tagashira E (1992) Inhibitory effect of beta-alanyl-L-histidinato zinc on bone resorption in tissue culture. Pharmacology 45:292–300

    Article  CAS  PubMed  Google Scholar 

  11. Shaw JC (1988) Copper deficiency and non-accidental injury. Arch Dis Child 63:448–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Rucker RB, Murray J, Riggins RS (1977) Nutritional copper deficiency and penicillamine administration: some effects on bone collagen and arterial elastin crosslinking. Adv Exp Med Biol 86B:619–648

    Article  CAS  PubMed  Google Scholar 

  13. Tranquilli AL, Lucino E, Garzetti GG, Romanini C (1994) Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecol Endocrinol 8:55–58

    Article  CAS  PubMed  Google Scholar 

  14. Katsumata S, Tsuboi R, Uehara M, Suzuki K (2006) Dietary iron deficiency decreases serum osteocalcin concentration and bone mineral density in rats. Biosci Biotechnol Biochem 70:2547–2550

    Article  CAS  PubMed  Google Scholar 

  15. Leek JC, Vogler JB, Gershwin ME, Golub MS, Hurley LS et al (1984) Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects. Am J Clin Nutr 40:1203–1212

    PubMed  Google Scholar 

  16. Da CFR, Marquiegui IM, Elizaga IV (1989) Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton. Teratology 39:181–194

    Article  Google Scholar 

  17. Oner G, Bhaumick B, Bala RM (1984) Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats. Endocrinology 114:1860–1863

    Article  CAS  PubMed  Google Scholar 

  18. Medeiros DM, Plattner A, Jennings D, Stoecker B (2002) Bone morphology, strength and density are compromised in iron-deficient rats and exacerbated by calcium restriction. J Nutr 132:3135–3141

    CAS  PubMed  Google Scholar 

  19. Parelman M, Stoecker B, Baker A, Medeiros D (2006) Iron restriction negatively affects bone in female rats and mineralization of hFOB osteoblast cells. Exp Biol Med (Maywood) 231:378–386

    CAS  Google Scholar 

  20. Rico H, Roca-Botran C, Hernandez ER, Seco C, Paez E et al (2000) The effect of supplemental copper on osteopenia induced by ovariectomy in rats. Menopause 7:413–416

    Article  CAS  PubMed  Google Scholar 

  21. Rico H, Gomez-Raso N, Revilla M, Hernandez ER, Seco C et al (2000) Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitomeric study. Eur J Obstet Gynecol Reprod Biol 90:97–101

    Article  CAS  PubMed  Google Scholar 

  22. Ronaghy HA, Reinhold JG, Mahloudji M, Ghavami P, Fox MR et al (1974) Zinc supplementation of malnourished schoolboys in Iran: increased growth and other effects. Am J Clin Nutr 27:112–121

    CAS  PubMed  Google Scholar 

  23. Gur A, Colpan L, Nas K, Cevik R, Sarac J et al (2002) The role of trace minerals in the pathogenesis of postmenopausal osteoporosis and a new effect of calcitonin. J Bone Miner Metab 20:39–43

    Article  CAS  PubMed  Google Scholar 

  24. Mutlu M, Argun M, Kilic E, Saraymen R, Yazar S (2007) Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. J Int Med Res 35:692–695

    Article  CAS  PubMed  Google Scholar 

  25. Hyun TH, Barrett-Connor E, Milne DB (2004) Zinc intakes and plasma concentrations in men with osteoporosis: the Rancho Bernardo Study. Am J Clin Nutr 80:715–721

    CAS  PubMed  Google Scholar 

  26. Strause L, Saltman P, Smith KT, Bracker M, Andon MB (1994) Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 124:1060–1064

    CAS  PubMed  Google Scholar 

  27. D’Amelio P, Cristofaro MA, Tamone C, Morra E, Di Bella S et al (2008) Role of iron metabolism and oxidative damage in postmenopausal bone loss. Bone 43:1010–1015

    Article  PubMed  Google Scholar 

  28. Marquardt ML, Done SL, Sandrock M, Berdon WE, Feldman KW (2012) Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants. Pediatrics 130:e695–e698

    Article  PubMed  Google Scholar 

  29. Relea P, Revilla M, Ripoll E, Arribas I, Villa LF et al (1995) Zinc, biochemical markers of nutrition, and type I osteoporosis. Age Ageing 24:303–307

    Article  CAS  PubMed  Google Scholar 

  30. Liu SZ, Yan H, Xu P, Li JP, Zhuang GH et al (2009) Correlation analysis between bone mineral density and serum element contents of postmenopausal women in Xi’an urban area. Biol Trace Elem Res 131:205–214

    Article  CAS  PubMed  Google Scholar 

  31. Arikan DC, Coskun A, Ozer A, Kilinc M, Atalay F et al (2011) Plasma selenium, zinc, copper and lipid levels in postmenopausal Turkish women and their relation with osteoporosis. Biol Trace Elem Res 144:407–417

    Article  CAS  PubMed  Google Scholar 

  32. Okyay E, Ertugrul C, Acar B, Sisman AR, Onvural B et al (2013) Comparative evaluation of serum levels of main minerals and postmenopausal osteoporosis. Maturitas 76:320–325

    Article  CAS  PubMed  Google Scholar 

  33. Yamaguchi M, Ozaki K (1990) Aging affects cellular zinc and protein synthesis in the femoral diaphysis of rats. Res Exp Med (Berl) 190:295–300

    Article  CAS  Google Scholar 

  34. Segawa Y, Tsuzuike N, Tagashira E, Yamaguchi M (1993) Preventive effect of beta-alanyl-L-histidinato zinc on the deterioration of bone metabolism in ovariectomized rats. Biol Pharm Bull 16:486–489

    Article  CAS  PubMed  Google Scholar 

  35. Yamaguchi M, Uchiyama S (2003) Preventive effect of zinc acexamate administration in streptozotocin-diabetic rats: restoration of bone loss. Int J Mol Med 12:755–761

    CAS  PubMed  Google Scholar 

  36. Hashizume M, Yamaguchi M (1993) Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells. Mol Cell Biochem 122:59–64

    Article  CAS  PubMed  Google Scholar 

  37. Hashizume M, Yamaguchi M (1994) Effect of beta-alanyl-L-histidinato zinc on differentiation of osteoblastic MC3T3-E1 cells: increases in alkaline phosphatase activity and protein concentration. Mol Cell Biochem 131:19–24

    Article  CAS  PubMed  Google Scholar 

  38. Yamaguchi M, Kishi S (1996) Zinc compounds inhibit osteoclast-like cell formation at the earlier stage of rat marrow culture but not osteoclast function. Mol Cell Biochem 158:171–177

    Article  CAS  PubMed  Google Scholar 

  39. Yamaguchi M, Uchiyama S (2004) Receptor activator of NF-kappaB ligand-stimulated osteoclastogenesis in mouse marrow culture is suppressed by zinc in vitro. Int J Mol Med 14:81–85

    CAS  PubMed  Google Scholar 

  40. Zou W, Hakim I, Tschoep K, Endres S, Bar-Shavit Z (2001) Tumor necrosis factor-alpha mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism. J Cell Biochem 83:70–83

    Article  CAS  PubMed  Google Scholar 

  41. Yamaguchi M, Inamoto K (1986) Differential effects of calcium-regulating hormones on bone metabolism in weanling rats orally administered zinc sulfate. Metabolism 35:1044–1047

    Article  CAS  PubMed  Google Scholar 

  42. Yamaguchi M, Yamaguchi R (1986) Action of zinc on bone metabolism in rats. Increases in alkaline phosphatase activity and DNA content. Biochem Pharmacol 35:773–777

    Article  CAS  PubMed  Google Scholar 

  43. Yamaguchi M, Kitajima T (1991) Effect of estrogen on bone metabolism in tissue culture: enhancement of the steroid effect by zinc. Res Exp Med (Berl) 191:145–154

    Article  CAS  Google Scholar 

  44. Dahl SL, Rucker RB, Niklason LE (2005) Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries. Cell Transplant 14:367–374

    Article  PubMed  Google Scholar 

  45. Rucker RB, Kosonen T, Clegg MS, Mitchell AE, Rucker BR et al (1998) Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr 67:996S–1002S

    CAS  PubMed  Google Scholar 

  46. Milkovic L, Hoppe A, Detsch R, Boccaccini AR, Zarkovic N (2013) Effects of Cu-doped 45S5 bioactive glass on the lipid peroxidation-associated growth of human osteoblast-like cells in vitro. J Biomed Mater Res A. doi:10.1002/jbm.a.35032

    Google Scholar 

  47. Ding H, Gao YS, Wang Y, Hu C, Sun Y, et al. (2014) Dimethyloxaloylglycine increases the bone healing capacity of adipose-derived stem cells by promoting osteogenic differentiation and angiogenic potential. DOI: 10.1089/scd.2013.0486.

  48. Sato K, Nohtomi K, Demura H, Takeuchi A, Kobayashi T et al (1997) Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin D production in renal tubules. Bone 21:57–64

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The project was supported by the Guangzhou Municipal Science and Technology Project (11C32060748) and the National Natural Science Foundation of China (81100728).

Author information

Authors and Affiliations

  1. Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China

    Jianmao Zheng, Xueli Mao, Junqi Ling & Jingjing Quan

  2. Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China

    Jianmao Zheng, Xueli Mao, Junqi Ling & Jingjing Quan

  3. Guangdong Provincial Institute of Public Health, Center for Disease Prevention and Control of Guangdong Provinice, Guangzhou, Guangdong, China

    Qun He

Authors
  1. Jianmao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xueli Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junqi Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingjing Quan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junqi Ling.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, J., Mao, X., Ling, J. et al. Low Serum Levels of Zinc, Copper, and Iron as Risk Factors for Osteoporosis: a Meta-analysis. Biol Trace Elem Res 160, 15–23 (2014). https://doi.org/10.1007/s12011-014-0031-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0031-7

Keywords

Search

Navigation