Osteoporosis International

, Volume 18, Issue 9, pp 1297–1305 | Cite as

Prediction of bone loss using biochemical markers of bone turnover

  • J. Lenora
  • K. K. Ivaska
  • K. J. Obrant
  • P. Gerdhem
Original Article



The association between baseline levels of eleven bone turnover markers and 5-year rate of bone density change was prospectively studied in a population-based sample of 601 75-year-old women. Several bone formation and resorption markers as well as urinary osteocalcin were modestly correlated to rate of bone density change.


Prediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly.


Eleven bone turnover markers were analyzed in 75-year old women in the OPRA study (n = 601) and compared to the 5-year change of areal bone mineral density (aBMD) in seven skeletal regions.


Annual aBMD change varied between +0.4% (spine) and −2.0% (femoral neck). Significant associations (p < 0.01) were found for four different serum osteocalcins (S-OCs) (standardized regression coefficient −0.20 to −0.22), urinary deoxypyridinoline (−0.19), serum TRACP5b (−0.19), serum CTX-I (−0.21), two of the three urinary osteocalcins (U-OCs) (−0.16) and aBMD change of the leg region (derived from the total body measurement). After adjustment for baseline aBMD, associations were found for all S-OCs (−0.11 to −0.16), two of the three U-OCs (−0.14 to −0.16) and aBMD change at the total hip, and for three of the four S-OCs (−0.14 to −0.15), S-TRACP5b (−0.11), two of the three U-OCs (−0.14 to −0.15) and aBMD change at the femoral neck. There were no significant results concerning aBMD change at the spine.


This study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women.


Bone density Bone loss Bone turnover markers Elderly 



Financial support was received from the Swedish Medical Research Council, Malmö University Hospital Funds, and the Greta and Johan Kock Foundation.

Conflict of interest statement

None of the authors has a conflict of interest.


  1. 1.
    Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ 3rd, O’Neill T, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20:1185–1194PubMedCrossRefGoogle Scholar
  2. 2.
    Stewart A, Kumar V, Reid DM (2006) Long-term fracture prediction by DXA and QUS: a 10-year prospective study. J Bone Miner Res 21:413–418PubMedCrossRefGoogle Scholar
  3. 3.
    Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, Pettersson K, Vaananen HK, Akesson K, Obrant KJ (2004) Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 19:386–393PubMedCrossRefGoogle Scholar
  4. 4.
    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 11:1531–1538PubMedGoogle Scholar
  5. 5.
    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 15:1526–1536PubMedCrossRefGoogle Scholar
  6. 6.
    Sornay-Rendu E, Munoz F, Duboeuf F, Delmas PD (2005) Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study. J Bone Miner Res 20:1929–1935PubMedCrossRefGoogle Scholar
  7. 7.
    Nguyen TV, Center JR, Eisman JA (2005) Femoral neck bone loss predicts fracture risk independent of baseline BMD. J Bone Miner Res 20:1195–1201PubMedCrossRefGoogle Scholar
  8. 8.
    Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C, Kelaghan J (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res 14:1583–1595PubMedCrossRefGoogle Scholar
  9. 9.
    Sarkar S, Reginster JY, Crans GG, Diez-Perez A, Pinette KV, Delmas PD (2004) Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res 19:394–401PubMedCrossRefGoogle Scholar
  10. 10.
    Rogers A, Hannon RA, Eastell R (2000) Biochemical markers as predictors of rates of bone loss after menopause. J Bone Miner Res 15:1398–1404PubMedCrossRefGoogle Scholar
  11. 11.
    Lofman O, Magnusson P, Toss G, Larsson L (2005) Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study. Clin Chim Acta 356:67–75PubMedCrossRefGoogle Scholar
  12. 12.
    Chapurlat RD, Gamero P, Sornay-Rendu E, Arlot ME, Claustrat B, Delmas PD (2000) Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women. Osteoporos Int 11:493–498PubMedCrossRefGoogle Scholar
  13. 13.
    Bauer DC, Sklarin PM, Stone KL, Black DM, Nevitt MC, Ensrud KE, Arnaud CD, Genant HK, Garnero P, Delmas PD, Lawaetz H, Cummings SR (1999) Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. J Bone Miner Res 14:1404–1410PubMedCrossRefGoogle Scholar
  14. 14.
    Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD (1999) Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14:1614–1621PubMedCrossRefGoogle Scholar
  15. 15.
    Melton LJ 3rd, Atkinson EJ, O’Connor MK, O’Fallon WM, Riggs BL (2000) Determinants of bone loss from the femoral neck in women of different ages. J Bone Miner Res 15:24–31PubMedCrossRefGoogle Scholar
  16. 16.
    Stepan JJ, Havrdova E, Tyblova M, Horakova D, Ticha V, Novakova I, Zikan V (2004) Markers of bone remodeling predict rate of bone loss in multiple sclerosis patients treated with low dose glucocorticoids. Clin Chim Acta 348:147–154PubMedCrossRefGoogle Scholar
  17. 17.
    Dresner-Pollak R, Parker RA, Poku M, Thompson J, Seibel MJ, Greenspan SL (1996) Biochemical markers of bone turnover reflect femoral bone loss in elderly women. Calcif Tissue Int 59:328–333PubMedCrossRefGoogle Scholar
  18. 18.
    Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10:384–391PubMedCrossRefGoogle Scholar
  19. 19.
    Obrant KJ, Ivaska KK, Gerdhem P, Alatalo SL, Pettersson K, Vaananen HK (2005) Biochemical markers of bone turnover are influenced by recently sustained fracture. Bone 36:786–792PubMedCrossRefGoogle Scholar
  20. 20.
    Gluer CC, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK (1995) Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int 5:262–270PubMedCrossRefGoogle Scholar
  21. 21.
    Kakonen SM, Hellman J, Karp M, Laaksonen P, Obrant KJ, Vaananen HK, Lovgren T, Pettersson K (2000) Development and evaluation of three immunofluorometric assays that measure different forms of osteocalcin in serum. Clin Chem 46:332–337PubMedGoogle Scholar
  22. 22.
    Hellman J, Kakonen SM, Matikainen MT, Karp M, Lovgren T, Vaananen HK, Pettersson K (1996) Epitope mapping of nine monoclonal antibodies against osteocalcin: combinations into two-site assays affect both assay specificity and sample stability. J Bone Miner Res 11:1165–1175PubMedCrossRefGoogle Scholar
  23. 23.
    Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK (2000) Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 15:1337–1345PubMedCrossRefGoogle Scholar
  24. 24.
    Ivaska KK, Hellman J, Likojarvi J, Kakonen SM, Gerdhem P, Akesson K, Obrant KJ, Pettersson K, Vaananen HK (2003) Identification of novel proteolytic forms of osteocalcin in human urine. Biochem Biophys Res Commun 306:973–980PubMedCrossRefGoogle Scholar
  25. 25.
    Ivaska KK, Kakonen SM, Gerdhem P, Obrant KJ, Pettersson K, Vaananen HK (2005) Urinary osteocalcin as a marker of bone metabolism. Clin Chem 51:618–628PubMedCrossRefGoogle Scholar
  26. 26.
    Halleen JM, Alatalo SL, Janckila AJ, Woitge HW, Seibel MJ, Vaananen HK (2001) Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption. Clin Chem 47:597–600PubMedGoogle Scholar
  27. 27.
    Janckila AJ, Takahashi K, Sun SZ, Yam LT (2001) Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. Clin Chem 47:74–80PubMedGoogle Scholar
  28. 28.
    Halleen JM, Ylipahkala H, Alatalo SL, Janckila AJ, Heikkinen JE, Suominen H, Cheng S, Vaananen HK (2002) Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density. Calcif Tissue Int 71:20–25PubMedCrossRefGoogle Scholar
  29. 29.
    Akesson K, Kakonen SM, Josefsson PO, Karlsson MK, Obrant KJ, Pettersson K (2005) Fracture-induced changes in bone turnover: a potential confounder in the use of biochemical markers in osteoporosis. J Bone Miner Metab 23:30–35PubMedCrossRefGoogle Scholar
  30. 30.
    Srivastava AK, Mohan S, Singer FR, Baylink DJ (2002) A urine midmolecule osteocalcin assay shows higher discriminatory power than a serum midmolecule osteocalcin assay during short-term alendronate treatment of osteoporotic patients. Bone 31:62–69PubMedCrossRefGoogle Scholar
  31. 31.
    Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11(Suppl 6):S2–S17PubMedCrossRefGoogle Scholar
  32. 32.
    Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R (1996) Bone density change and biochemical indices of skeletal turnover. Calcif Tissue Int 58:236–243PubMedGoogle Scholar
  33. 33.
    Iki M, Morita A, Ikeda Y, Sato Y, Akiba T, Matsumoto T, Nishino H, Kagamimori S, Kagawa Y, Yoneshima H (2006) Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study. Osteoporos Int 17:1086–1095PubMedCrossRefGoogle Scholar
  34. 34.
    Bruyere O, Collette J, Delmas P, Rouillon A, Roux C, Seidel L, Richy F, Reginster JY (2003) Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women. Maturitas 44:259–265PubMedCrossRefGoogle Scholar
  35. 35.
    Iki M, Kajita E, Dohi Y, Nishino H, Kusaka Y, Tsuchida C, Yamamoto K, Ishii Y (1996) Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women. Maturitas 25:59–67PubMedCrossRefGoogle Scholar
  36. 36.
    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 6:399–406PubMedCrossRefGoogle Scholar
  37. 37.
    Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R (2002) Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30:886–890PubMedCrossRefGoogle Scholar
  38. 38.
    Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD (2000) Serum type I collagen breakdown product (serum CTX) predicts hip fracture risk in elderly women: the EPIDOS study. Bone 27:283–286PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • J. Lenora
    • 1
  • K. K. Ivaska
    • 1
  • K. J. Obrant
    • 1
  • P. Gerdhem
    • 1
    • 2
  1. 1.Clinical and Molecular Osteoporosis Research Unit, Department of Orthopaedics, Malmö University HospitalLund UniversityMalmöSweden
  2. 2.Department of Orthopaedics, Karolinska University HospitalKarolinska InstituteStockholmSweden

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