Skip to main content

Advertisement

SpringerLink
Log in

Genetic and Constitutional Influences on Bone Turnover Markers: A Study of Male Twin Pairs

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Biochemical markers of bone turnover originating from type I procollagen synthesis or type I collagen breakdown were examined in men using a classic twin study design based on monozygotic (MZ) and dizygotic (DZ) twins. The aim was to estimate the influence of heredity (genes and shared family childhood elements) and constitutional factors in determining procollagen type I amino-terminal propeptide (PINP), type I collagen carboxy-terminal telopeptide (ICTP), and urinary amino-terminal type I collagen telopeptide (NTx) marker levels in a sample of in 98 MZ and 108 DZ male twin pairs. We are not aware of any prior studies conducted in men that address the influence of genetic factors on bone turnover marker variability. The findings support a dominant role for heredity in the variation of bone resorption marker levels in men, with additive genetic effects explaining two-thirds of the variance in the bone resorption markers NTx and ICTP. Genetic factors may contribute less for PINP, a marker of bone formation. The genetic loci influencing PINP or NTx and body weight/disc axial area, although related in part, appeared to be largely independent, indicating that genetic effects on bone turnover are unlikely to be to a large degree a result of genetic regulation of individual body weight.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Bjarnason NH, Sarkar S, Duong T, Mitlak B, Delmas PD, Christiansen C (2001) Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos Int 12:922–930

    Article  PubMed  CAS  Google Scholar 

  2. Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PJ, Delmas PD (1996) Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 11:1531–1538

    PubMed  CAS  Google Scholar 

  3. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536

    Article  PubMed  CAS  Google Scholar 

  4. Riggs BL, Khosla S (1995) Role of biochemical markers in assessment of osteoporosis. Acta Orthop Scand Suppl 266:14–18

    PubMed  CAS  Google Scholar 

  5. Srivastava AK, Vliet EL, Lewiecki EM, Maricic M, Abdelmalek A, Gluck O, Baylink DJ (2005) Clinical use of serum and urine bone markers in the management of osteoporosis. Curr Med Res Opin 21:1015–1026

    Article  PubMed  CAS  Google Scholar 

  6. Pouilles JM, Tremollieres FA, Ribot C (2006) Osteoporosis in otherwise healthy perimenopausal and early postmenopausal women: physical and biochemical characteristics. Osteoporos Int 17:193–200

    Article  PubMed  CAS  Google Scholar 

  7. Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest 100:1755–1759

    Article  PubMed  CAS  Google Scholar 

  8. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A (1996) Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 81:4358–4365

    Article  PubMed  CAS  Google Scholar 

  9. Donescu OS, Battie MC, Videman T, Risteli J, Eyre D (2005) Anthropometrics and biochemical markers in men. J Clin Densitom 8:222–227

    Article  PubMed  Google Scholar 

  10. Watts NB (1999) Clinical utility of biochemical markers of bone remodeling. Clin Chem 45:1359–1368

    PubMed  CAS  Google Scholar 

  11. Szulc P, Delmas PD (2001) Biochemical markers of bone turnover in men. Calcif Tissue Int 69:229–234

    Article  PubMed  CAS  Google Scholar 

  12. Hobson EE, Ralston RH (2001) Role of genetic factors in the pathophysiology and management of osteoporosis. Clin Endocrinol (Oxf) 54:1–9

    Article  CAS  Google Scholar 

  13. Risteli J, Risteli L (1997) Assays of type I procollagen domains and collagen fragments: problems to be solved and future trends. Scand J Clin Lab Invest 57(suppl 227):105–113

    Article  CAS  Google Scholar 

  14. Khosla S, Kleerekoper M (1999) Biochemical markers of bone turnover. In: Favus MJ (ed) Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Lippincott Williams, Wilkins, Philadelphia, pp 128–134

    Google Scholar 

  15. Hanley DA (2000) Biochemical markers of bone turnover. In: Golzman D, Henderson JE (eds) The Osteoporosis Primer. Cambridge University Press, Cambridge, pp 239–252

    Google Scholar 

  16. Garnero P, Arden NK, Griffiths G, Delmas PD, Spector TD (1996) Genetic influence on bone turnover in postmenopausal twins. Clin Endocrinol Metab 81:140–146

    Article  CAS  Google Scholar 

  17. Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA (1991) Genetic factors in bone turnover. J Clin Endocrinol Metab 72:808–813

    PubMed  CAS  Google Scholar 

  18. 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 78:1461–1466

    Article  PubMed  CAS  Google Scholar 

  19. 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 16:371–378

    Article  PubMed  CAS  Google Scholar 

  20. Battié MC, Videman T, Gibbons L, Fisher LD, Manninen H, Gill K (1995) Determinants of lumbar disc degeneration: a study relating lifetime exposures and MRI findings in identical twins. Spine 20:2601–2612

    Article  PubMed  Google Scholar 

  21. Sarna S, Kaprio J, Sistonen P, Koskenvuo M (1978) Diagnosis of twin zygosity by mailed questionnaire. Hum Hered 28:241–254

    Article  PubMed  CAS  Google Scholar 

  22. Simonen RL, Videman T, Kaprio J, Levalahti E, Battie MC (2003) Factors associated with exercise lifestyle – a study of monozygotic twins. Int J Sports Med 24:499–505

    Article  PubMed  CAS  Google Scholar 

  23. Videman T, Battie MC, Gibbons LE, Vanninen E, Kaprio J, Koskenvuo M (2002) The roles of adulthood behavioural factors and familial influences in bone density among men. Ann Med 34:434–443

    Article  PubMed  CAS  Google Scholar 

  24. Neale MC, Cardon LR (1992) Methodology for Genetic Studies of Twins and Families. Kluwer Academic, Dordrecht, the Netherlands

    Google Scholar 

  25. Akaike H (1987) Factor analysis and AIC. Psychometrika 52:317–332

    Article  Google Scholar 

  26. Stata Corporation (2005) Stata statistical software: release 9.2. College Station, TX

    Google Scholar 

  27. Neale MC, Walters EE, Eaves LJ, Maes HH, Kendler KS (1994) Multivariate genetic analysis of twin-family data on fears: Mx models. Behav Genet 24:119–139

    Article  PubMed  CAS  Google Scholar 

  28. Falconer DS (1981) Introduction to Quantitative Genetics, 2nd ed. Longman, New York

    Google Scholar 

  29. Valimaki VV, Piippo K, Valimaki S, Loyttyniemi E, Kontula K, Valimaki MJ (2005) The relation of the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene to peak bone mass and bone turnover rate among young healthy men. Osteoporos Int 16:1633–1640

    Article  PubMed  CAS  Google Scholar 

  30. Van Pottelbergh I, Lumbroso S, Goemaere S, Sultan C, Kaufman JM (2001) Lack of influence of the androgen receptor gene CAG-repeat polymorphism on sex steroid status and bone metabolism in elderly men. Clin Endocrinol (Oxf) 55:659–666

    Article  Google Scholar 

  31. Khosla S, Riggs BL, Atkinson EJ, Oberg AL, Mavilia C, Del Monte F, Melton LJ 3rd, Brandi ML (2004) Relationship of estrogen receptor genotypes to bone mineral density and to rates of bone loss in men. J Clin Endocrinol Metab 89:1808–1816

    Article  PubMed  CAS  Google Scholar 

  32. Sapir-Koren R, Livshits G, Kobyliansky E (2003) Genetic effects of estrogen receptor alpha and collagen IA1 genes on the relationships of parathyroid hormone and 25 hydroxyvitamin D with bone mineral density in Caucasian women. Metabolism 52:1129–1135

    Article  PubMed  CAS  Google Scholar 

  33. Hansen MA, Overgaard K, Riis BJ, Christiansen C (1991) Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study. BMJ 303:961–964

    PubMed  CAS  Google Scholar 

  34. Uebelhart D, Schlemmer A, Johansen JS, Gineyts E, Christiansen C, Delmas PD (1991) Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab72:367–373

    Article  PubMed  CAS  Google Scholar 

  35. Smerdely P, Seller M, Smith A, Day P, Diamond T (2000) Predictors of bone mass in healthy older men in the community. Med J Aust 173:183–186

    PubMed  CAS  Google Scholar 

  36. Compston J (2001) Secondary causes of osteoporosis in men. Calcif Tissue Int 69:193–195

    Article  PubMed  CAS  Google Scholar 

  37. Tanaka T, Latorre MR, Jaime PC, Florindo AA, Pippa MG, Zerbini CA (2001) Risk factors for proximal femur osteoporosis in men aged 50 years or older. Osteoporos Int 12:942–949

    Article  PubMed  CAS  Google Scholar 

  38. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    Article  PubMed  CAS  Google Scholar 

  39. Christgau S (2000) Circadian variation in serum CrossLaps concentration is reduced in fasting individuals. Clin Chem 46:431

    PubMed  CAS  Google Scholar 

  40. Rosen CJ, Tenenhouse A (1998) Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad Med 104:101–102, 107–110, 113–114

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by the National Institutes of Health, USA (AR 40857); the Academy of Finland (38332 and 42044); the Alberta Heritage Foundation for Medical Research, Canada; the CIHR Canada Research Chairs Program; and EURODISC (QLK6-CT-2002-02582). O. S. D. was supported by the Alberta Provincial CIHR Training Program in Bone and Joint Health.

Author information

Authors and Affiliations

  1. Faculty of Rehabilitation Medicine, University of Alberta, 3-50 Corbett Hall, Edmonton, Alberta, T6G 2G4, Canada

    O. S. Donescu & T. Videman

  2. Department of Physical Therapy, University of Alberta, 2-50 Corbett Hall, Edmonton, Alberta, T6G 2G4, Canada

    M. C. Battié

  3. Finnish Twin Cohort Study, Department of Public Health, University of Helsinki, P.O. Box 41, (Mannerheimintie 172), FIN-00014, Helsinki, Finland

    J. Kaprio & E. Levalahti

  4. Department of Clinical Chemistry, University of Oulu, 90014, Oulu, Finland

    J. Risteli

  5. Department of Orthopedics and Sports Medicine, University of Washington, 1959 N.E. Pacific Street, Box 356500, Seattle, WA, 98195-6500, USA

    D. Eyre

Authors
  1. O. S. Donescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. C. Battié
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Kaprio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Levalahti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Risteli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Eyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Videman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. S. Donescu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donescu, O.S., Battié, M.C., Kaprio, J. et al. Genetic and Constitutional Influences on Bone Turnover Markers: A Study of Male Twin Pairs. Calcif Tissue Int 80, 81–88 (2007). https://doi.org/10.1007/s00223-006-0210-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-006-0210-4

Keywords

Search

Navigation