Skip to main content

Genetic Predisposition for Osteoporosis and Fractures in Postmenopausal Women

  • Chapter
  • First Online:
Advancements and Innovations in Health Sciences

Abstract

Osteoporosis is a disease with complex etiology where the genetic factors may account for as much as 50–85% of the risk of its development in postmenopausal women. The polymorphism of estrogen receptor genes (ESR1, ESR2) seems essential among the genetic factors. The goal of this study was to analyze polymorphisms of selected genes in a population of postmenopausal women treated for osteoporosis and to evaluate the influence of genetic and nongenetic factors on the estimated 10-year risk of fracture. The study group consisted of 214 women hospitalized for treatment of postmenopausal osteoporosis. We investigated the presence of ESR1, ESR2, LRP5, and WNT16 genetic polymorphisms and the risk of fracture in each woman. The main finding was that of significant differences in the polymorphisms of the WNT16 rs2908004 genetic variant, notably, the less frequent presence of TC allele in women with a greater risk of osteoporotic fractures. We conclude that the polymorphism of the WNT16 gene seems highly relevant in the pathogenesis of osteoporosis, which makes it a promising object for further research on the genetic background of fracture risk.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Albagha OME, Pettersson U, Stewart A, McGuigan FEA, MacDonald HM, Reid DM, Ralston SH (2005) Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone. J Med Genet 42:240–246

    Article  CAS  Google Scholar 

  • Becherini L, Gennari L, Masi L, Mansani R, Massart F, Morelli A, Falchetti A, Gonnelli S, Fiorelli G, Tanini A, Brandi ML (2000) Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor-alpha gene and their relationship to bone mass variation in postmenopausal Italian women. Hum Mol Genet 9:2043–2050

    Article  CAS  Google Scholar 

  • Bord S, Horner A, Beavan S, Compston J (2001) Estrogen receptors α and β are differentially expressed in developing human bone. J Clin Endocrinol Metab 86:2309–2314

    CAS  PubMed  Google Scholar 

  • Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346(20):1513–1521

    Article  CAS  Google Scholar 

  • Colin EM, Uitterlinden AG, Meurs JBJ, Bergink AP, van de Klift M, Fang Y, Arp PP, Hofman A, van Leeuwen JPTM, Pols HAP (2003) Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk. J Clin Endocrinol Metab 88:3777–3784

    Article  CAS  Google Scholar 

  • Del Real A, Riancho-Zarrabeitia L, López-Delgado L, Riancho JA (2018) Epigenetics of skeletal diseases. Curr Osteoporos Rep 16(3):246–255

    Article  Google Scholar 

  • Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE (2004) Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 74:866–875

    Article  CAS  Google Scholar 

  • García-Ibarbia C, Pérez-Núñez MI, Olmos JM (2013) Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry, and fractures. Osteoporos Int 24(9):2449–2454

    Article  Google Scholar 

  • Ichikawa S, Koller DL, Peacock M, Johnson ML, Lai D, Hui SL, Johnston CC, Foroud TM, Econs MJ (2005) Polymorphisms in the estrogen receptor β (ESR2) gene are associated with bone mineral density in Caucasian men and women. J Clin Endocrinol Metab 90(11):5921–5927

    Article  CAS  Google Scholar 

  • Kanis JA, on behalf of the World Health Organisation Scientific Group (2007) Assessment of osteoporosis at the primary health care level. WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield

    Google Scholar 

  • Kanis JA, Oden A, Johansson H, Borgström F, Ström O, McCloskey E (2009) FRAX® and its applications to clinical practice. Bone 44:734–774

    Article  Google Scholar 

  • Koller DL, Zheng HF, Karasik D (2013) Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women. J Bone Miner Res 28(3):547–558

    Article  CAS  Google Scholar 

  • Lorentzon M, Mellstrom D, Ohlsson C (2005) Age of attainment of peak bone mass is site-specific in Swedish men―The GOOD Study. J Bone Miner Res 20:1223–1227

    Article  Google Scholar 

  • Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, Ohta T, Kishino T, Matsumoto N, Minakami H, Niikawa N, Yoshiura K (2004) LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. J Hum Genet 49:80–86

    Article  CAS  Google Scholar 

  • Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492(1):1–18

    Article  CAS  Google Scholar 

  • Mozioğlu E, Akgöz M, Tamerler C, Kocagöz ZT (2014) A simple guanidinium isothiocyanate method for bacterial genomic DNA isolation. Turk J Biol 38:125–129

    Article  Google Scholar 

  • Ogawa S, Hosoi T, Shiraki M, Orimo H, Emi M, Muramatsu M, Ouchi Y, Inoue S (2000) Association of estrogen receptor β gene polymorphism with bone mineral density. Biochem Biophys Res Commun 269:537–541

    Article  CAS  Google Scholar 

  • Ralston SH, Uitterlinden AG (2010) Genetics of osteoporosis. Endocr Rev 31(5):629–662

    Article  CAS  Google Scholar 

  • Richards JB, Kavvoura FK, Rivadeneira F et al (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 151(8):528–537

    Article  Google Scholar 

  • Sowers M, Jannausch ML, Liang W, Willing M (2004) Estrogen receptor genotypes and their association with the 10-year changes in bone mineral density and osteocalcin concentrations. J Clin Endocrinol Metab 89:733–739

    Article  CAS  Google Scholar 

  • Stewart TL, Ralston SH (2000) Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol 166:235–245

    Article  CAS  Google Scholar 

  • van Meurs JB, Schuit SC, Weel AE, van der Klift M, Bergink AP, Arp PP, Colin EM, Fang Y, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG (2003) Association of 5-prime estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet 12:1745–1754

    Article  Google Scholar 

  • Zheng HF, Tobias JH, Duncan E et al (2012) WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet 8(7):e1002745

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ernest Kuchar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mitek, T., Nagraba, Ł., Deszczyński, J., Stolarczyk, M., Kuchar, E., Stolarczyk, A. (2019). Genetic Predisposition for Osteoporosis and Fractures in Postmenopausal Women. In: Pokorski, M. (eds) Advancements and Innovations in Health Sciences. Advances in Experimental Medicine and Biology(), vol 1211. Springer, Cham. https://doi.org/10.1007/5584_2019_413

Download citation

Publish with us

Policies and ethics