Skip to main content

Bone Turnover Markers

  • Chapter
  • First Online:
Principles of Bone and Joint Research

Abstract

Bone is a very active tissue that is constantly remodeled in order to adapt to mechanic or metabolic requirements. Since disturbances in bone remodeling may result in relevant skeletal diseases, there is great interest in tools to assess bone remodeling for scientific and clinical applications. Bone turnover markers (BTMs) are among these tools; this chapter presents established markers of bone resorption and bone formation and also selected novel markers. For each marker the biochemical background will be described; in addition you will learn about non-pathological and pathological conditions that lead to alterations of the levels of BTMs. Finally, strengths and weaknesses of the BTMs – especially with regard to their potential clinical applications – will be discussed.

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

Access this chapter

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

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Similar content being viewed by others

References

  1. Johansson H, Oden A, Kanis JA, et al. A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif Tissue Int. 2014;94:560–7.

    Article  CAS  PubMed  Google Scholar 

  2. Vasikaran S, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011;22:391–420.

    Article  CAS  PubMed  Google Scholar 

  3. Vasikaran S, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory medicine. Position on bone markers standards in osteoporosis. Clin Chem Lab Med. 2011;49:1271–4.

    Article  CAS  PubMed  Google Scholar 

  4. Garnero P, Ferreras M, Karsdal MA, Nicamhlaoibh R, Risteli J, Borel O, Qvist P, Delmas PD, Foged NT, Delaissè JM. The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003;18:859–67.

    Article  CAS  PubMed  Google Scholar 

  5. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Vaananen HK. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab. 2006;52:499–509.

    CAS  PubMed  Google Scholar 

  6. Fahrleitner-Pammer A, Herberth J, Browning SR, Obermayer-Pietsch B, Wirnsberger G, Holzer H, Dobnig H, Malluche HH. Bone markers predict cardiovascular events in chronic kidney disease. J Bone Miner Res. 2008;23:1850–8.

    Article  CAS  PubMed  Google Scholar 

  7. Melkko J, Niemi S, Risteli L, Risteli J. Radioimmunoassay for the carboxyterminal propeptide of human type I procollagen (PICP). Clin Chem. 1990;36:1328–32.

    CAS  PubMed  Google Scholar 

  8. Melkko J, et al. Immunoassay for intact amino-terminal propeptide of human type I procollagen. Clin Chem. 1996;42:947–54.

    CAS  PubMed  Google Scholar 

  9. Vergnaud P, et al. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women; the EPIDOS study. J Clin Endocrinol Metab. 1997;82:719–24.

    CAS  PubMed  Google Scholar 

  10. Pietschmann P, Skalicky M, Kneissel M, Rauner M, Hofbauer G, Stupphann D, Viidik A. Bone structure and metabolism in a rodent model of male senile osteoporosis. Exp Gerontol. 2007;42:1099–108.

    Article  CAS  PubMed  Google Scholar 

  11. Sipos W, Zysset P, Kostenuik P, Mayrhofer E, Bogdan C, Rauner M, Stolina M, Dwyer D, Sommerfeld-Stur I, Pendl G, Resch H, Dall’Ara E, Varga P, Pietschmann P. OPG-Fc treatment in growing pigs leads to rapid reduction in bone resorption markers, serum calcium, and bone formation markers. Horm Metab Res. 2011;43:944–9.

    Article  CAS  PubMed  Google Scholar 

  12. Rauner M, Föger-Samwald U, Kurz MF, Brünner-Kubath C, Schamall D, Kapfenberger A, Varga P, Kudlacek S, Wutzl A, Höger H, Zysset PK, Shi GP, Hofbauer LC, Sipos W, Pietschmann P. Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture. Bone. 2014;64:281–7.

    Article  CAS  PubMed  Google Scholar 

  13. Garnero P. New developments in biological markers of bone metabolism. Bone. 2014;66:46–55.

    Article  CAS  PubMed  Google Scholar 

  14. Bonnet N, Garnero P, Ferrari S. Periostin action in bone. Mol Cell Endocrinol. 2016;432:75–82.

    Article  CAS  PubMed  Google Scholar 

  15. Merle B, Garnero P. The multiple facets of periostin in bone metabolism. Osteoporos Int. 2012;23:1199–212.

    Article  CAS  PubMed  Google Scholar 

  16. Rousseau JC, Sornay-Rendu E, Bertholon C, Chapurlat R, Garnero P. Serum periostin is associated with fracture risk in postmenopausal women: a 7 years prospective analysis of the OFELY study. J Clin Endocrinol Metab. 2014;99:2533–9.

    Article  CAS  PubMed  Google Scholar 

  17. Kerschan-Schindl K, Ebenbichler G, Gruther W, Petrikic A, Föger-Samwald U, Kudlacek S, Patsch J, Jaksch P, Klepetko W, Pietschmann P. Serum levels of musculoskeletal markers of lung transplantation recipients (manuscript in preparation).

    Google Scholar 

  18. Murali SK, Roschger P, Zeitz U, Klaushofer K, Andrukhova O, Erben RG. FGF23 regulates bone mineralization in a 1,25(OH)2 D3 and Klotho-independent manner. J Bone Miner Res. 2016;31(1):129–42.

    Article  CAS  PubMed  Google Scholar 

  19. Lian JB, Stein HS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T, et al. Micro RNA control of bone formation and homeostasis. Nat Rev Endocrinol. 2012;8:212–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sugatani T, Hruska KA. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem. 2009;284:4667–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Weilner S, Schraml E, Wieser M, Messner P, Schneider K, Wasermann K, Micutkova L, Fortschegger K, Maier AB, Westendorp R, Resch H, Wolbank S, Redl H, Jamsen-Dürr P, Pietschmann P, Grillari-Voglauer R, Grillari J. Secreted microvascular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. Aging Cell. 2016;15:744–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Weilner S, Skalicky S, Salzer B, Keider V, Wagner M, Hildner F, Gabriel C, Dovjak P, Pietschmann P, Grillari-Voglauer R, Grillari J, Hackl M. Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation. Bone. 2015;79:43–51.

    Article  CAS  PubMed  Google Scholar 

  23. Michelsen J, Wallaschofski H, Friedrich N, Spelhagen C, Rettig R, Ittermann T, Nauck M, Hannemann A. Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone. 2013;57:399–404.

    Article  CAS  PubMed  Google Scholar 

  24. Kerschan-Schindl K, Thalmann M, Sodeck GH, Skenderi K, Matalas AL, Grampp S, Ebner C, Pietschmann P. A 246-km continuous running race causes significant changes in bone metabolism. Bone. 2009;45:1079–83.

    Article  CAS  PubMed  Google Scholar 

  25. Kerschan-Schindl K, Thalmann M, Weiss E, Tsironi M, Föger-Samwald U, Meinhart J, Skenderi K, Pietschmann P. Changes in serum levels of myokines and Wnt-antagonists after and ultramarathon race. PLoS One. 2015;10:e0132478.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lombardi G, Sanchis-Gomar F, Perego S, Sansoni V, Banfi G. Implications of exercise-induced adipo-myokines in bone metabolism. Endocrine. 2016;54:284–305.

    Article  CAS  PubMed  Google Scholar 

  27. Cavalier E, Bergmann P, Bruyere O, Delanaye P, Durnez A, Devogelaer JP, Ferrari SL, Gielen E, Goemare S, Kaufmann JM, Nzeusseu Toukap A, Reginster JY, Rousseau AF, Rozenberg S, Scheen AJ, Body JJ. The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club. Osteoporos Int. 2016;27:2181–95.

    Article  CAS  PubMed  Google Scholar 

  28. Bergmann P, Body JJ, Boonen S, et al. Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club. Int J Clin Pract. 2009;63:19–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bandeira F, Costa AG, Filho MAS, Pimentel L, Lima L, Bilezikian JP. Bone markers and osteoporosis therapy. Arq Bras Endocrinol Metab. 2014;58:504–13.

    Article  Google Scholar 

  30. Ensrud KE, Barrett-Connor EL, Schwartz A, Santora AC, Bauer DC, Suryawanshi S, Feldstein A, Haskell WL, Hochberg MC, Torner JC, Lombardi A, Black DM, Fracture Intervention Trial Long-Term Extension Research Group. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res. 2004;19:1259–69.

    Article  CAS  PubMed  Google Scholar 

  31. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J, Amg Bone Loss Study Group. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008;43:222–9.

    Article  CAS  PubMed  Google Scholar 

  32. Glover S, Eastell R, McCloskey EV, Rogers A, Garnero P, Lowery J, Belleli R, Wright TM, John MR. Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Bone. 2009;45:1053–8.

    Article  CAS  PubMed  Google Scholar 

  33. Bouxsein ML, Delmas PD. Considerations for development of surrogate endpoints for antifracture efficacy of new treatments in osteoporosis: a perspective. J Bone Miner Res. 2008;23:1155–67.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kerschan-Schindl K, Mikosch P, Obermayer-Pietsch B, Gasser RW, Dimai HP, Fahrleitner-Pammer A, Dobnig H, Roschger P, Preisinger E, Klaushofer K, Resch H, Pietschmann P. Current controversies in clinical management of postmenopausal osteoporosis. Exp Clin Endocrinol Diabetes. 2014;122:437–44.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katharina Kerschan-Schindl .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Kerschan-Schindl, K., Föger-Samwald, U., Pietschmann, P. (2017). Bone Turnover Markers. In: Pietschmann, P. (eds) Principles of Bone and Joint Research. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-319-58955-8_4

Download citation

Publish with us

Policies and ethics