Skip to main content
SpringerLink
Log in

Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

This longitudinal twin study documented that genetic factors explain 44–56% of the between-individual variance in bone loss at femoral neck, lumbar spine, and forearm in postmenopausal Caucasian women, providing a rationale for identifying the specific genes involved.

Introduction

Although there is a significant genetic effect on peak BMD, until recently, no substantive studies on heritability of bone loss in human were available. The aim of the study was to estimate the heritability of the bone loss at multiple sites in postmenopausal Caucasian women.

Methods

Postmenopausal female monozygotic (MZ) and dizygotic (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry and followed up for an average of 8 years (range 5–14 years). All twins were noncurrent hormone replacement therapy users and not on any osteoporosis treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip, lumbar spine, and forearm several times (range 2–9) during the follow-up period. Individual bone losses at femoral neck, lumbar spine, and forearm were estimated by linear regression modeling. Structural equation modeling was utilized to estimate the heritability of the bone loss.

Results

A total of 712 postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins had slightly higher bone loss at lumbar spine, but similar at femoral neck and forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the bone loss at all sites were significantly higher in MZ than DZ twin pairs (p = 0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm, respectively), indicating a significant genetic influence on bone loss at these sites. After adjustment for age at baseline and weight change during the follow-up, the heritability estimate was 47% (95% CI 27–63%) for bone loss at femoral neck, 44% (95% CI 27–58%) for lumbar spine, and 56% (95% CI 44–65%) for forearm.

Conclusions

Our data suggest that up to 56% of the between-individual variance in bone loss is due to genes, providing a rationale to identify specific genetic factors for bone loss.

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

Similar content being viewed by others

References

  1. Bainbridge KE, Sowers M, Lin X, Harlow SD (2004) Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women. Osteoporos Int 15(6):439–446

    Article  PubMed  Google Scholar 

  2. Guthrie JR, Ebeling PR, Hopper JL, Barrett-Connor E, Dennerstein L, Dudley EC, Burger HG, Wark JD (1998) A prospective study of bone loss in menopausal Australian-born women. Osteoporos Int 8(3):282–290

    Article  PubMed  CAS  Google Scholar 

  3. Zhai G, Hart DJ, Valdes AM, Kato BS, Richards JB, Hakim A, Spector TD (2008) Natural history and risk factors for bone loss in postmenopausal Caucasian women: a 15-year follow-up population-based study. Osteoporos Int 19:1211–1217

    Article  PubMed  CAS  Google Scholar 

  4. Keen RW, Nguyen T, Sobnack R, Perry LA, Thompson PW, Spector TD (1996) Can biochemical markers predict bone loss at the hip and spine?: a 4-year prospective study of 141 early postmenopausal women. Osteoporos Int 6(5):399–406

    Article  PubMed  CAS  Google Scholar 

  5. Hansen MA, Overgaard K, Christiansen C (1995) Spontaneous postmenopausal bone loss in different skeletal areas—followed up for 15 years. J Bone Miner Res 10(2):205–210

    PubMed  CAS  Google Scholar 

  6. Christian JC, Yu PL, Slemenda CW, Johnston CC Jr (1989) Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet 44(3):429–433

    PubMed  CAS  Google Scholar 

  7. Slemenda CW, Christian JC, Reed T, Reister TK, Williams CJ, Johnston CC Jr (1992) Long-term bone loss in men: effects of genetic and environmental factors. Ann Intern Med 117(4):286–291

    PubMed  CAS  Google Scholar 

  8. Kelly PJ, Nguyen T, Hopper J, Pocock N, Sambrook P, Eisman J (1993) Changes in axial bone density with age: a twin study. J Bone Miner Res 8(1):11–17

    PubMed  CAS  Google Scholar 

  9. Hui SL, Koller DL, Foroud TM, Econs MJ, Johnston CC, Peacock M (2006) Heritability of changes in bone size and bone mass with age in premenopausal white sisters. J Bone Miner Res 21(7):1121–1125

    Article  PubMed  Google Scholar 

  10. Makovey J, Nguyen TV, Naganathan V, Wark JD, Sambrook PN (2007) Genetic effects on bone loss in peri- and postmenopausal women: a longitudinal twin study. J Bone Miner Res 22(11):1773–1780

    Article  PubMed  Google Scholar 

  11. Andrew T, Hart DJ, Snieder H, de Lange M, Spector TD, MacGregor AJ (2001) Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. Twin Res 4(6):464–477

    Article  PubMed  CAS  Google Scholar 

  12. Nguyen ND, Center JR, Eisman JA, Nguyen TV (2007) Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women. J Bone Miner Res 22(8):1147–1154

    Article  PubMed  Google Scholar 

  13. Neale MC (1994) Mx: statistical modeling, 2nd edn. Box 710 MCV, Richmond, VA 23298: Department of Psychiatry. 2nd edition

  14. Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6(6):561–567

    PubMed  CAS  Google Scholar 

  15. Dequeker J, Nijs J, Verstraeten A, Geusens P, Gevers G (1987) Genetic determinants of bone mineral content at the spine and radius: a twin study. Bone 8(4):207–209

    Article  PubMed  CAS  Google Scholar 

  16. Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 11(4):530–534

    PubMed  CAS  Google Scholar 

  17. Lutz J (1986) Bone mineral, serum calcium, and dietary intakes of mother/daughter pairs. Am J Clin Nutr 44(1):99–106

    PubMed  CAS  Google Scholar 

  18. Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10(12):2017–2022

    Article  PubMed  CAS  Google Scholar 

  19. Harris M, Nguyen TV, Howard GM, Kelly PJ, Eisman JA (1998) Genetic and environmental correlations between bone formation and bone mineral density: a twin study. Bone 22(2):141–145

    Article  PubMed  CAS  Google Scholar 

  20. Tokita A, Kelly PJ, Nguyen TV, Qi JC, Morrison NA, Risteli L, Risteli J, Sambrook PN, Eisman JA (1994) Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover. J Clin Endocrinol Metab 78(6):1461–1466

    Article  PubMed  CAS  Google Scholar 

  21. Hunter D, De Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD (2001) Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res 16(2):371–378

    Article  PubMed  CAS  Google Scholar 

  22. Sowers MF, Kshirsagar A, Crutchfield MM, Updike S (1992) Joint influence of fat and lean body composition compartments on femoral bone mineral density in premenopausal women. Am J Epidemiol 136(3):257–265

    PubMed  CAS  Google Scholar 

  23. Blain H, Carriere I, Favier F, Jeandel C, Papoz L (2004) Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study. Calcif Tissue Int 75(1):32–39

    Article  PubMed  CAS  Google Scholar 

  24. Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP (2000) Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 15(4):710–720

    Article  PubMed  CAS  Google Scholar 

  25. Nguyen TV, Sambrook PN, Eisman JA (1998) Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res 13(9):1458–1467

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank all the twins and many staff at the TRU including Ursula Perks, Gail Clement, Juliet Baker, Liisa Carter, Liisa Bevan, Lucy Campbell, Feng Zhang, Jane Unwin, Zarko Stephan, who participated in this study and performed the bone density scans.

Sources of support: The Arthritis Research Campaign; The Wellcome Trust

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Twin Research and Genetic Epidemiology Unit, King’s College London School of Medicine, St Thomas’ Hospital Campus, Westminster Bridge Road, London, SE1 7EH, UK

    G. Zhai, T. Andrew, B. S. Kato & T. D. Spector

  2. Division of Imaging Sciences, King’s College London, Guy’s Campus, London, SE1 9RT, UK

    G. M. Blake

Authors
  1. G. Zhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Andrew
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. S. Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. M. Blake
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. D. Spector
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Zhai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhai, G., Andrew, T., Kato, B.S. et al. Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study. Osteoporos Int 20, 949–953 (2009). https://doi.org/10.1007/s00198-008-0751-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-008-0751-7

Keywords

Search

Navigation