Skip to main content
SpringerLink
Log in

Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Associations between polymorphisms of the osteoprotegerin gene (OPG) and bone mineral density (BMD) have been studied by several research groups, but results are mixed. Accordingly, the authors performed a meta-analysis on studies of associations between OPG polymorphisms and BMD. Appropriate studies were identified using MEDLINE and by manual searching. A total of eight separate comparisons were considered in this meta-analysis. Individuals with the GG genotype of G1181C were found to have a significantly lower mean lumbar BMD than subjects with the CC genotype (WMDs −0.051 g/cm2, 95% confidence interval −0.079−−0.023, P < 0.001), and similar results were obtained in European and Asian populations. In contrast to G1181C, no association was found between the A163G and T950C polymorphisms and lumbar BMD. In terms of femoral neck BMD, the GG genotype of G1181C was associated with a significantly lower BMD than the CC genotype in Europeans but not in Asians. Total hip BMD was lower for the GG genotype of G1181C than for the CC or GC genotypes in Europeans. A difference in total hip BMD was found between the AG and GG genotypes of the A163G polymorphism by meta-analyses in Europeans, but no differences were found between the genotypes of the T950C polymorphism and total hip BMD in Europeans. Summarizing, the present study demonstrates that the OPG G1181C polymorphism is associated with lumbar BMD in Europeans and Asians, and with femoral neck and total hip BMD in Europeans only.

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

Similar content being viewed by others

References

  1. Nguyen TV, Blangero J, Eisman JA (2000) Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res 15:392–401

    Article  CAS  PubMed  Google Scholar 

  2. Zmuda JM, Cauley JA, Ferrell RE (1999) Recent progress in understanding the genetic susceptibility to osteoporosis. Genet Epidemiol 16:356–367

    Article  CAS  PubMed  Google Scholar 

  3. Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 9(Suppl 1):S1

    Article  PubMed  Google Scholar 

  4. Reid P, Holen I (2008) Pathophysiological roles of osteoprotegerin (OPG). Eur J Cell Biol 88:1–17

    Article  CAS  PubMed  Google Scholar 

  5. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268

    Article  CAS  PubMed  Google Scholar 

  6. Garcia-Unzueta MT, Riancho JA, Zarrabeitia MT, Sanudo C, Berja A, Valero C, Pesquera C, Paule B, Gonzalez-Macias J, Amado JA (2008) Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density. Horm Metab Res 40:219–224

    Article  CAS  PubMed  Google Scholar 

  7. Moffett SP, Oakley JI, Cauley JA, Lui LY, Ensrud KE, Taylor BC, Hillier TA, Hochberg MC, Li J, Cayabyab S, Lee JM, Peltz G, Cummings SR, Zmuda JM (2008) Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women. J Clin Endocrinol Metab 93:2002–2008

    Article  CAS  PubMed  Google Scholar 

  8. Kim JG, Kim JH, Kim JY, Ku SY, Jee BC, Suh CS, Kim SH, Choi YM (2007) Association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women. Menopause 14:913–918

    Article  PubMed  Google Scholar 

  9. Ueland T, Bollerslev J, Wilson SG, Dick IM, Islam FM, Mullin BH, Devine A, Prince RL (2007) No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women. Bone 40:175–181

    Article  CAS  PubMed  Google Scholar 

  10. Zhao HY, Liu JM, Ning G, Zhao YJ, Zhang LZ, Sun LH, Xu MY, Uitterlinden AG, Chen JL (2005) The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporos Int 16:1519–1524

    Article  CAS  PubMed  Google Scholar 

  11. Yamada Y, Ando F, Niino N, Shimokata H (2003) Association of polymorphisms of the osteoprotegerin gene with bone mineral density in Japanese women but not men. Mol Genet Metab 80:344–349

    Article  CAS  PubMed  Google Scholar 

  12. Langdahl BL, Carstens M, Stenkjaer L, Eriksen EF (2002) Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res 17:1245–1255

    Article  CAS  PubMed  Google Scholar 

  13. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537

    CAS  PubMed  Google Scholar 

  14. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  PubMed  Google Scholar 

  15. Davey Smith G, Egger M (1997) Meta-analyses of randomised controlled trials. Lancet 350:1182

    Article  CAS  PubMed  Google Scholar 

  16. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  17. Zajickova K, Zemanova A, Hill M, Zofkova I (2008) Is A163G polymorphism in the osteoprotegerin gene associated with heel velocity of sound in postmenopausal women? Physiol Res 57(Suppl 1):S153–S157

    CAS  PubMed  Google Scholar 

  18. Arko B, Prezelj J, Kocijancic A, Komel R, Marc J (2005) Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas 51:270–279

    Article  CAS  PubMed  Google Scholar 

  19. Jorgensen HL, Kusk P, Madsen B, Fenger M, Lauritzen JB (2004) Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab 22:132–138

    Article  CAS  PubMed  Google Scholar 

  20. Arko B, Prezelj J, Komel R, Kocijancic A, Hudler P, Marc J (2002) Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab 87:4080–4084

    Article  CAS  PubMed  Google Scholar 

  21. Ohmori H, Makita Y, Funamizu M, Hirooka K, Hosoi T, Orimo H, Suzuki T, Ikari K, Nakajima T, Inoue I, Hata A (2002) Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis. J Hum Genet 47:400–406

    Article  CAS  PubMed  Google Scholar 

  22. Hsu YH, Niu T, Terwedow HA, Xu X, Feng Y, Li Z, Brain JD, Rosen CJ, Laird N (2006) Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. Hum Genet 118:568–577

    Article  CAS  PubMed  Google Scholar 

  23. Choi JY, Shin A, Park SK, Chung HW, Cho SI, Shin CS, Kim H, Lee KM, Lee KH, Kang C, Cho DY, Kang D (2005) Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif Tissue Int 77:152–159

    Article  CAS  PubMed  Google Scholar 

  24. Wynne F, Drummond F, O’Sullivan K, Daly M, Shanahan F, Molloy MG, Quane KA (2002) Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1 polymorphisms on BMD in the Irish population. Calcif Tissue Int 71:26–35

    Article  CAS  PubMed  Google Scholar 

  25. Brandstrom H, Gerdhem P, Stiger F, Obrant KJ, Melhus H, Ljunggren O, Kindmark A, Akesson K (2004) Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women. Calcif Tissue Int 74:18–24

    Article  CAS  PubMed  Google Scholar 

  26. Soufi M, Schoppet M, Sattler AM, Herzum M, Maisch B, Hofbauer LC, Schaefer JR (2004) Osteoprotegerin gene polymorphisms in men with coronary artery disease. J Clin Endocrinol Metab 89:3764–3768

    Article  CAS  PubMed  Google Scholar 

  27. Wada T, Nakashima T, Hiroshi N, Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12:17–25

    Article  CAS  PubMed  Google Scholar 

  28. Song C, Jin B (2005) TRAIL (CD253), a new member of the TNF superfamily. J Biol Regul Homeost Agents 19:73–77

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A084794).

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee, Jin-Hyun Woo, Seong Jae Choi, Jong Dae Ji & Gwan Gyu Song

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Hyun Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seong Jae Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong Dae Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.H., Woo, JH., Choi, S.J. et al. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep 37, 227–234 (2010). https://doi.org/10.1007/s11033-009-9637-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9637-9

Keywords

Search

Navigation