Osteoporosis International

, Volume 22, Issue 2, pp 391–420 | Cite as

Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards

  • S. Vasikaran
  • R. Eastell
  • O. Bruyère
  • A. J. Foldes
  • P. Garnero
  • A. Griesmacher
  • M. McClung
  • H. A. Morris
  • S. Silverman
  • T. Trenti
  • D. A. Wahl
  • C. Cooper
  • J. A. Kanis
  • for the IOF-IFCC Bone Marker Standards Working Group
Position Paper

Abstract

Summary

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical studies.

Introduction

Bone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda.

Methods

Evidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and 2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001.

Results

High levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control. IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine.

Conclusion

BTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in part resolved by adopting international reference standards.

Keywords

Bone makers Bone turnover Fracture risk IOF Monitoring treatment Reference standards 

References

  1. 1.
    Consensus Development Conference (1993) Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 94:646–650CrossRefGoogle Scholar
  2. 2.
    Kanis JA, Johnell O (2005) Requirements for DXA for the management of osteoporosis in Europe. Osteoporos Int 16:229–238PubMedCrossRefGoogle Scholar
  3. 3.
    Burge R, Dawson-Hughes B, Solomon D, Wong J, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22:465–475PubMedCrossRefGoogle Scholar
  4. 4.
    Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ, Khaltaev N (2008) A reference standard for the description of osteoporosis. Bone 42:467–475PubMedCrossRefGoogle Scholar
  5. 5.
    Kanis JA, Melton LJ, Christiansen C, Johnston C, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141PubMedCrossRefGoogle Scholar
  6. 6.
    Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026PubMedCrossRefGoogle Scholar
  7. 7.
    MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, Mojica W, Timmer M, Alexander A et al (2008) Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 148:197–213PubMedGoogle Scholar
  8. 8.
    Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster J-Y, Borgstrom F, Rizzoli R, on behalf of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) (2008) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 19:399–428PubMedCrossRefGoogle Scholar
  9. 9.
    Bergmann P, Body JJ, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, Reginster JY, Gangji V (2009) 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 63:19–26PubMedCrossRefGoogle Scholar
  10. 10.
    Vesper H, Cosman F, Endres DB, Garnero P, Hoyle NR, Kleerekoper M, Mallinak NJ (2004) Application of biochemical markers of bone turnover in the assessment and monitoring of bone diseases—approved guidelines. NCCLS document C48-A. ISBN 1-56238-539-9Google Scholar
  11. 11.
    Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS, Dooley KC, Don-Wauchope A, Douville P et al (2009) Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 42:929–942PubMedCrossRefGoogle Scholar
  12. 12.
    Szulc P, Delmas P (2008) Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int 19:1683–1704PubMedCrossRefGoogle Scholar
  13. 13.
    Vasikaran SD (2008) Utility of biochemical markers of bone turnover and bone mineral density in management of osteoporosis. Crit Rev Clin Lab Sci 45:221–258PubMedCrossRefGoogle Scholar
  14. 14.
    Hannon R, Eastell R (2000) Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 11:S30–S44PubMedCrossRefGoogle Scholar
  15. 15.
    Seibel MJ, Lang M, Geilenkeuser WJ (2001) Interlaboratory variation of biochemical markers of bone turnover. Clin Chem 47:1443–1450PubMedGoogle Scholar
  16. 16.
    Eisman J, Ebeling P, Ewald D, Flicker L, Holborow B, Nash P, Sambrook P, Seibel M, Stenmark J, Winzenberg T, Herjandono J (2010) Clinical guideline for the prevention and treatment of osteoporosis in postmenopausal women and older men. The Royal Australian College of General Practitioners. www.racgp.org.au. Accessed March 2010
  17. 17.
    Sociedad Iberoamericana de Osteología y Metabolismo Mineral (SIBOMM) (2009) Ibero-American consensus on osteoporosis (Osteoporosis: Prevención, Diagnóstico y Tratamiento). www.aaomm.org.ar. Accessed March 2010
  18. 18.
    Lorenc R, Głuszko P, Karczmarewicz E, Księżopolska-Orłowska K, Misiorowski W, Franek E, Horst-Sikorska W, Kaleta M, Męczekalski B et al (2007) Recommendations on the diagnosis and treatment of osteoporosis. Reducing the incidence of fractures through effective prevention and treatment. Terapia 9:11–39Google Scholar
  19. 19.
    Singapore Ministry of Health (2008) Clinical practice guidelines for osteoporosis. Ministry of Health, Singapore. www.moh.gov.sg/cpg. Accessed March 2010
  20. 20.
    National Osteoporosis Guideline Group (2008) Osteoporosis—clinical guideline for prevention and treatment—executive summary. www.shef.ac.uk/NOGG. Accessed March 2010
  21. 21.
    Dawson-Hughes B, Lindsay R, Khosla S, Melton LJ, Tosteson AN, Favus MJ, Baim S (2008) Clinician’s guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation. www.nof.org. Accessed March 2010
  22. 22.
    Nelson HD, Morris CD, Kraemer DF, Mahon S, Carney N, Nygren PM, Helfand M (2001) Osteoporosis in postmenopausal women: diagnosis and monitoring. Evidence report/technology assessment no. 28. Agency for Healthcare Research and Quality, RockvilleGoogle Scholar
  23. 23.
    Civitelli R, Armamento-Villareal R, Napoli N (2009) Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int 20:843–851PubMedCrossRefGoogle Scholar
  24. 24.
    Leeming D, Alexandersen P, Karsdal M, Qvist P, Schaller S, Tankó L (2006) An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice. Eur J Clin Pharmacol 62:781–792PubMedCrossRefGoogle Scholar
  25. 25.
    Wickham C, Walsh K, Cooper C, Barker D, Margetts B, Morris J, Bruce S (1989) Dietary calcium, physical activity, and risk of hip fracture: a prospective study. Br Med J Clin Res Ed 299:889–892CrossRefGoogle Scholar
  26. 26.
    Huopio J, Kröger H, Honkanen R, Saarikoski S, Alhava E (2000) Risk factors for perimenopausal fractures: a prospective study. Osteoporos Int 11:219–227PubMedCrossRefGoogle Scholar
  27. 27.
    Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87:1586–1592PubMedCrossRefGoogle Scholar
  28. 28.
    Darby AJ, Meunier PJ (1981) Mean wall thickness and formation periods of trabecular bone packets in idiopathic osteoporosis. Calcif Tissue Int 33:199–204PubMedCrossRefGoogle Scholar
  29. 29.
    Jilka RL (2003) Biology of the basic multicellular unit and the pathophysiology of osteoporosis. Med Pediatr Oncol 41:182–185PubMedCrossRefGoogle Scholar
  30. 30.
    Garnero P, Sornay-Rendu E, Capuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337–349PubMedCrossRefGoogle Scholar
  31. 31.
    Chesnut CH, Bell NH, Clark GS, Drinkwater BL, English SC, Johnson CCJ, Notelovitz M, Rosen C, Cain DF, Flessland KA, Mallinak NJ (1997) Hormone replacement therapy in postmenopausal women: urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med 102:29–37PubMedCrossRefGoogle Scholar
  32. 32.
    Peichl P, Griesmacher A, Pointinger P, Marteau R, Hartl W, Gruber W, Bröll H (1998) Association between female sex hormones and biochemical markers of bone turnover in peri- and postmenopausal women. Calcif Tissue Int 62:388–394PubMedCrossRefGoogle Scholar
  33. 33.
    Christiansen C, Riis BJ, Rodbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet 1:1105–1108PubMedCrossRefGoogle Scholar
  34. 34.
    Christiansen C, Riis BJ, Rodbro P (1990) Screening procedures for women at risk of developing postmenopausal osteoporosis. Osteoporos Int 1:35–40PubMedCrossRefGoogle Scholar
  35. 35.
    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
  36. 36.
    Mole PA, Walkinshaw MH, Robins SP, Paterson CR (1992) Can urinary pyridinium crosslinks and urinary oestrogens predict bone mass and rate of bone loss after the menopause? Eur J Clin Investig 22:767–771CrossRefGoogle Scholar
  37. 37.
    Reeve J, Pearson J, Mitchell A, Green J, Nicholls A, Justice J, Hudson E, Klenerman L (1995) Evolution of spinal bone loss and biochemical markers of bone remodelling after menopause in normal women. Calcif Tissue Int 57:105–110PubMedCrossRefGoogle Scholar
  38. 38.
    Rosen CJ, Chesnut CH, Mallinak NJ (1997) The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement therapy or calcium supplementation. J Clin Endocrinol Metab 82:1904–1910PubMedCrossRefGoogle Scholar
  39. 39.
    Ross PD, Knowlton W (1998) Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res 13:297–302PubMedCrossRefGoogle Scholar
  40. 40.
    Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C (1996) Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 19:9–12PubMedCrossRefGoogle Scholar
  41. 41.
    Finigan J, Greenfield D, Blumsohn A, Hannon R, Peel N, Jiang G, Eastell R (2008) Risk factors for vertebral and nonvertebral fracture over 10 years: a population-based study in women. J Bone Miner Res 23:75–85PubMedCrossRefGoogle Scholar
  42. 42.
    Dempster DW (2000) The contribution of trabecular architecture to cancellous bone quality. J Bone Miner Res 15:20–23PubMedCrossRefGoogle Scholar
  43. 43.
    Follet H, Boivin G, Rumelhart C, Meunier PJ (2004) The degree of mineralization is a determinant of bone strength: a study on human calcanei. Bone 34:783–789PubMedCrossRefGoogle Scholar
  44. 44.
    Banse X, Sims TJ, Bailey AJ (2002) Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. J Bone Miner Res 17:1621–1628PubMedCrossRefGoogle Scholar
  45. 45.
    Viguet-Carin S, Roux JP, Arlot ME, Merabet Z, Leeming DJ, Byrjalsen I, Delmas PD, Bouxsein ML (2006) Contribution of the advanced glycation end product pentosidine and of maturation of type I collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 39:1073–1079CrossRefGoogle Scholar
  46. 46.
    Bauer DC (2001) Biochemical markers of bone turnover: the Study of Osteoporotic Fracture. In: Eastell R, Baumann M, Hoyle N, Wieczorek L (eds) Bone markers—biochemical and clinical perspectives. Martin Dunitz, London, pp 219–223Google Scholar
  47. 47.
    Dobnig H, Piswanger-Solkner JC, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Riedmuller G, Brueck C, Fahrleitner-Pammer A (2007) Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab 92:1678–1686PubMedCrossRefGoogle Scholar
  48. 48.
    Tromp AM, Ooms ME, Popp-Snijders C, Roos JC, Lips P (2000) Predictors of fractures in elderly women. Osteoporos Int 11:134–140PubMedCrossRefGoogle Scholar
  49. 49.
    Akesson K, Ljunghall S, Jonsson B, Sernbo I, Johnell O, Gärdsell P, Obrant KJ (1995) Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women. J Bone Miner Res 10:1823–1829PubMedCrossRefGoogle Scholar
  50. 50.
    Garnero P, Hausherr E, Chapuy M-C, 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 11:1531–1538PubMedCrossRefGoogle Scholar
  51. 51.
    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
  52. 52.
    Ross PD, Kress BC, Parson RE, Wasnich RD, Armour KA, Mizrahi IA (2000) Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int 11:76–82PubMedCrossRefGoogle Scholar
  53. 53.
    Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD (2005) Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res 20:1813–1819PubMedCrossRefGoogle Scholar
  54. 54.
    van Daele PL, Seibel MJ, Burger H, Hofman A, Grobbee DE, van Leeuwen JP, Birkenhager JC, Pols HA (1996) Case–control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study. BMJ 312:482–483PubMedGoogle Scholar
  55. 55.
    Vergnaud P, Garnero P, Meunier PJ, Breart G, Kamihagi K, Delmas PD (1997) Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS study. J Clin Endocrinol Metab 82:719–724PubMedCrossRefGoogle Scholar
  56. 56.
    Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1993) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest 91:1769–1774PubMedCrossRefGoogle Scholar
  57. 57.
    Chapurlat RD, Garnero P, Bréart 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
  58. 58.
    Luukinen H, Kakonen S-M, Pettersson K, Koski K, Laippala P, Lovgren T, Kivela S-L, Vaananen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15:2473–2478PubMedCrossRefGoogle Scholar
  59. 59.
    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
  60. 60.
    Greenfield DM, Hannon RA, Eastell R (2001) The association between bone turnover and fracture risk (Sheffield Osteoporosis study). In: Eastell R, Baumann M, Hoyle N, Wieczorek L (eds) Bone markers—biochemical and clinical perspectives. Martin Dunitz, London, pp 225–236Google Scholar
  61. 61.
    Garnero P, Cloos P, Sornay-Rendu E, Qvist PER, Delmas PD (2002) Type I collagen racemization and isomerization and the risk of fracture in postmenopausal women: the OFELY prospective study. J Bone Miner Res 17:826–833PubMedCrossRefGoogle Scholar
  62. 62.
    Bruyère O, Collette J, Delmas PD, Rouillon A, Roux C, Seidel L, Richy F, Reginster J-Y (2003) Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal women. Maturitas 44:259–265PubMedCrossRefGoogle Scholar
  63. 63.
    Melton LJ III, Crowson CS, O’Fallon WM, Wahner HW, Riggs BL (2003) Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 18:312–318PubMedCrossRefGoogle Scholar
  64. 64.
    Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA (2005) Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study. J Bone Miner Res 20:579–587PubMedCrossRefGoogle Scholar
  65. 65.
    Ivaska KK, Gerdhem P, Vaananen HK, Akesson K, Obrant KJ (2010) Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res 25:393–403PubMedCrossRefGoogle Scholar
  66. 66.
    Bauer DC, Garnero P, Harrison SL, Cauley JA, Eastell R, Ensrud KE, Orwoll E, Osteoporotic Fractures in Men (MrOS) Research Group (2009) Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study. J Bone Miner Res 24:2032–2038PubMedCrossRefGoogle Scholar
  67. 67.
    Johnell O, Oden A, De Laet C, Garnero P, Delmas PD, Kanis JA (2002) Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int 13:523–526PubMedCrossRefGoogle Scholar
  68. 68.
    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
  69. 69.
    Khosla S, Melton LJ, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274PubMedCrossRefGoogle Scholar
  70. 70.
    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
  71. 71.
    Stepan JJ, Pospichal J, Presl J, Pacovsky V (1987) Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women. Bone 8:279–284PubMedCrossRefGoogle Scholar
  72. 72.
    Kanis JA, on behalf of the World Health Organization Scientific Group (2008) Assessment of osteoporosis at the primary health-care level. Technical report, Sheffield, UK. WHO Collaborating Center, University of Sheffield. Available at http://www.shef.ac.uk/FRAX/index.htm. Accessed July 2009
  73. 73.
    Berry SD, Kiel DP, Donaldson MG, Cummings SR, Kanis JA, Johansson H, Samelson EJ (2010) Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: the Framingham Osteoporosis Study. Osteoporos Int 21:53–60PubMedCrossRefGoogle Scholar
  74. 74.
    Compston J, Cooper A, Cooper C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P, Wilkins M, for the National Osteoporosis Guideline Group (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62:105–108PubMedCrossRefGoogle Scholar
  75. 75.
    Fujiwara S, Nakamura T, Orimo H, Hosoi T, Gorai I, Oden A, Johansson H, Kanis JA (2008) Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX (TM)). Osteoporos Int 19:429–435PubMedCrossRefGoogle Scholar
  76. 76.
    Kanis JA, Black D, Cooper C, Dargent P, Dawson-Hughes B, De Laet C, Delmas PD, Eisman J, Johnell O, on behalf of the International Osteoporosis Foundation and the National Osteoporosis Foundation, USA et al (2002) A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int 13:527–536PubMedCrossRefGoogle Scholar
  77. 77.
    Lippuner K, Johansson H, Kanis JA, Rizzoli R (2010) FRAX (R) assessment of osteoporotic fracture probability in Switzerland. Osteoporos Int 21:381–389PubMedCrossRefGoogle Scholar
  78. 78.
    Riggs BL, Parfitt AM (2005) Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res 20:177–184PubMedCrossRefGoogle Scholar
  79. 79.
    Arlot M, Meunier PJ, Boivin G, Haddock L, Tamayo J, Correa-Rotter R, Jasqui S, Donley DW, Dalsky GP, Martin JS, Eriksen EF (2005) Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters. J Bone Miner Res 20:1244–1253PubMedCrossRefGoogle Scholar
  80. 80.
    McClung M, Lewiecki E, Cohen S, Bolognese M, Woodson G, Moffett A, Peacock M, Miller P, Lederman S et al (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831PubMedCrossRefGoogle Scholar
  81. 81.
    Vasikaran SD, Khan S, McCloskey EV, Kanis JA (1995) Sustained response to intravenous alendronate in postmenopausal osteoporosis. Bone Miner 17:517–520Google Scholar
  82. 82.
    Saag K, Lindsay R, Kriegman A, Beamer E, Zhou W (2007) A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone 40:1238–1243PubMedCrossRefGoogle Scholar
  83. 83.
    Chesnut CH, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, LeBoff M, Maricic M et al (2000) A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med 109:267–276PubMedCrossRefGoogle Scholar
  84. 84.
    Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel E-M et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468PubMedCrossRefGoogle Scholar
  85. 85.
    Bruyère O, Collette J, Rizzoli R, Decock C, Ortolani S, Cormier C, Detilleux J, Reginster J-Y (2010) Relationship between 3-month changes in biochemical markers of bone remodelling and changes in bone mineral density and fracture incidence in patients treated with strontium ranelate for 3 years. Osteoporos Int 21:1031–1036PubMedCrossRefGoogle Scholar
  86. 86.
    Naylor K, Clowes J, Finigan J, Paggiosi M, Peel N, Eastell R (2010) The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone 46:592–597PubMedCrossRefGoogle Scholar
  87. 87.
    Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282:637–645PubMedCrossRefGoogle Scholar
  88. 88.
    Prestwood K, Gunness M, Muchmore D, Lu Y, Wong M, Raisz L (2000) A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab 85:2197–2202PubMedCrossRefGoogle Scholar
  89. 89.
    Pereda C, Hannon R, Naylor K, Eastell R (2002) The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women. Br J Obstet Gynaecol 109:812–820CrossRefGoogle Scholar
  90. 90.
    Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut Iii CH, Brown J, Eriksen EF et al (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282:1344–1352PubMedCrossRefGoogle Scholar
  91. 91.
    Rosen C, Hochberg M, Bonnick S, McClung M, Miller P, Broy S, Kagan R, Chen E, Petruschke R, Thompson D, de Papp A (2005) Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res 20:141–151PubMedCrossRefGoogle Scholar
  92. 92.
    Hannon R, Clowes J, Eagleton A, Al H, Eastell R, Blumsohn A (2004) Clinical performance of immunoreactive tartrate-resistant acid phosphatase isoform 5b as a marker of bone resorption. Bone 34:187–194PubMedCrossRefGoogle Scholar
  93. 93.
    Emkey R, Delmas P, Bolognese M, Borges J, Cosman F, Ragi-Eis S, Recknor C, Zerbini C, Neate C, Sedarati F, Epstein S (2009) Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): additional results from the Monthly Oral Therapy With Ibandronate For Osteoporosis Intervention (MOTION) study. Clin Ther 31:751–761PubMedCrossRefGoogle Scholar
  94. 94.
    Delmas PD, Recker RR, Chesnut CH, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, Christiansen C (2004) Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporos Int 15:792–798PubMedCrossRefGoogle Scholar
  95. 95.
    Delmas P, Adami S, Strugala C, Stakkestad J, Reginster J, Felsenberg D, Christiansen C, Civitelli R, Drezner M et al (2006) Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study. Arthritis Rheum 54:1838–1846PubMedCrossRefGoogle Scholar
  96. 96.
    Miller P, McClung M, Macovei L, Stakkestad J, Luckey M, Bonvoisin B, Reginster J, Recker R, Hughes C et al (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20:1315–1322PubMedCrossRefGoogle Scholar
  97. 97.
    Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822PubMedCrossRefGoogle Scholar
  98. 98.
    Cummings SR, San MJ, McClung MR, Siris ES, Eastell R, Reid IR, Delmas PD, Zoog HB, Austin M et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765PubMedCrossRefGoogle Scholar
  99. 99.
    Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J (2008) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 93:2149–2157PubMedCrossRefGoogle Scholar
  100. 100.
    Lewiecki E, Miller P, McClung M, Cohen S, Bolognese M, Liu Y, Wang A, Siddhanti S, Fitzpatrick L (2007) Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22:1832–1841PubMedCrossRefGoogle Scholar
  101. 101.
    Glover S, Eastell R, McCloskey E, Rogers A, Garnero P, Lowery J, Belleli R, Wright T, John M (2009) Rapid and robust response of biochemical markers of bone formation to teriparatide therapy. Bone Miner 45:1053–1058Google Scholar
  102. 102.
    Greenspan S, Bone H, Ettinger M, Hanley D, Lindsay R, Zanchetta J, Blosch C, Mathisen A, Morris S, Marriott T (2007) Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 146:326–339PubMedGoogle Scholar
  103. 103.
    Black D, Bouxsein M, Palermo L, McGowan J, Newitt D, Rosen E, Majumdar S, Rosen C (2008) Randomized trial of once-weekly parathyroid hormone (1–84) on bone mineral density and remodeling. J Clin Endocrinol Metab 93:2166–2172PubMedCrossRefGoogle Scholar
  104. 104.
    Black D, Bilezikian J, Ensrud K, Greenspan S, Palermo L, Hue T, Lang T, McGowan J, Rosen C (2005) One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis. N Engl J Med 353:555–565PubMedCrossRefGoogle Scholar
  105. 105.
    Blake G, Compston J, Fogelman I (2009) Could strontium ranelate have a synergistic role in the treatment of osteoporosis? J Bone Miner Res 24:1354–1357PubMedCrossRefGoogle Scholar
  106. 106.
    Bone H, McClung M, Roux C, Recker R, Eisman J, Verbruggen N, Hustad C, DaSilva C, Santora A, Ince B (2010) Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 25:937–947PubMedGoogle Scholar
  107. 107.
    Garnero P, Shih W, Gineyts E, Karpf D, Delmas P (1994) Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 79:1693–1700PubMedCrossRefGoogle Scholar
  108. 108.
    Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M, Garnero P, Boonen S, Cauley JA, Black DM, Delmas PD, Eastell R (2009) Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States. J Bone Miner Res 24:389–397PubMedCrossRefGoogle Scholar
  109. 109.
    Glover SJ, Gamero P, Naylor K, Rogers A, Eastell R (2008) Establishing a reference range for bone turnover markers in young, healthy women. Bone 42:623–630PubMedCrossRefGoogle Scholar
  110. 110.
    de Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, Rosenberg E, Reitz RE (2007) A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 40:1222–1230PubMedCrossRefGoogle Scholar
  111. 111.
    Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O, Frediani B, Rossini M, on behalf of the BONTURNO study group (2008) Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 82:341–347PubMedCrossRefGoogle Scholar
  112. 112.
    Garnero P, Borel O, Delmas PD (2001) Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin Chem Lab Med 47:694–702Google Scholar
  113. 113.
    Garnero P, Vergnaud P, Hoyle N (2008) Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 54:188–196PubMedCrossRefGoogle Scholar
  114. 114.
    Rogers A, Glover SJ, Eastell R (2009) A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy. Bone 45:1044–1052PubMedCrossRefGoogle Scholar
  115. 115.
    Hannon R, Blumsohn A, Naylor K, Eastell R (1998) Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res 13:1124–1133PubMedCrossRefGoogle Scholar
  116. 116.
    Eastell R, Krege JH, Chen P, Glass EV, Reginster J-Y (2006) Development of an algorithm for using PINP to monitor treatment of patients with teriparatide. Curr Med Res Opin 22:61–66PubMedCrossRefGoogle Scholar
  117. 117.
    Greenspan S, Resnick N, Parker R (2005) Early changes in biochemical markers of bone turnover are associated with long-term changes in bone mineral density in elderly women on alendronate, hormone replacement therapy, or combination therapy: a three-year, double-blind, placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 90:2762–2767PubMedCrossRefGoogle Scholar
  118. 118.
    Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, Wagman RB (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970PubMedCrossRefGoogle Scholar
  119. 119.
    Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289PubMedCrossRefGoogle Scholar
  120. 120.
    Watts NB, Cooper C, Lindsay R, Eastell R, Manhart MD, Barton IP, van Staa TP, Adachi JD (2004) Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 7:255–261PubMedCrossRefGoogle Scholar
  121. 121.
    Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD (2002) Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 17:1–10PubMedCrossRefGoogle Scholar
  122. 122.
    Delmas PD, Seeman E (2004) Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:599–604PubMedCrossRefGoogle Scholar
  123. 123.
    Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056PubMedCrossRefGoogle Scholar
  124. 124.
    Reginster J-Y, Sarkar S, Zegels B, Henrotin Y, Bruyere O, Agnusdei D, Collette J (2004) Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with vertebral fracture risk. Bone 34:344–351PubMedCrossRefGoogle Scholar
  125. 125.
    Sarkar S, Reginster J-Y, 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
  126. 126.
    Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258PubMedCrossRefGoogle Scholar
  127. 127.
    Delmas PD, Munoz F, Black DM, Cosman F, Boonen S, Watts NB, Kendler D, Eriksen EF, Mesenbrink PG, Eastell R, The HORIZON-PFT Research Group (2009) Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J Bone Miner Res 24:1544–1551PubMedCrossRefGoogle Scholar
  128. 128.
    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 12:922–930PubMedCrossRefGoogle Scholar
  129. 129.
    Li Z, Meredith MP, Hoseyni MS (2002) A method to assess the proportion of treatment effect explained by a surrogate endpoint. Stat Med 20:7531–7588Google Scholar
  130. 130.
    Freedman LS, Graubard BI, Schatzkin A (1992) Statistical validation of intermediate endpoints for chronic diseases. Stat Med 11:167–178PubMedCrossRefGoogle Scholar
  131. 131.
    Eastell R, Hannon RA, Garnero P, Campbell MJ, Delmas PD (2007) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate: review of statistical analysis. J Bone Miner Res 22:1656–1660PubMedCrossRefGoogle Scholar
  132. 132.
    Bauer DC, Garnero P, Hochberg MC, Santora A, Delmas P, Ewing SK, Black DM (2006) Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial. J Bone Miner Res 21:292–299PubMedCrossRefGoogle Scholar
  133. 133.
    Veitch SW, Findlay SC, Hamer AJ, Blumsohn A, Eastell R, Ingle BM (2006) Changes in bone mass and bone turnover following tibial shaft fracture. Osteoporos Int 17:364–372PubMedCrossRefGoogle Scholar
  134. 134.
    Hansen M, Overgaard K, Riis B, Christiansen C (1991) Potential risk factors for development of postmenopausal osteoporosis—examined over a 12-year period. Osteoporos Int 1:95–102PubMedCrossRefGoogle Scholar
  135. 135.
    Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11:S2–S17PubMedCrossRefGoogle Scholar
  136. 136.
    McKiernan FE, Berg RL, Linneman JG (2010) The utility of BMD Z-score diagnostic thresholds for secondary causes of osteoporosis. Osteoporos Int. doi:10.1007/s00198-00010-01307-00191 Google Scholar
  137. 137.
    Seibel MJ, Naganathan V, Barton I, Grauer A (2004) Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate. J Bone Miner Res 19:323–329PubMedCrossRefGoogle Scholar
  138. 138.
    Delmas P, Licata A, Reginster J, Crans G, Chen P, Misurski D, Wagman R, Mitlak B (2006) Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone Miner 39:237–243Google Scholar
  139. 139.
    Collette J, Bruyère O, Kaufman J, Lorenc R, Felsenberg D, Spector T, Diaz-Curiel M, Boonen S, Reginster J (2010) Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover. Osteoporos Int 21:233–241PubMedCrossRefGoogle Scholar
  140. 140.
    Blouin J, Dragomir A, Ste-Marie LG, Fernandes JC, Perreault S (2007) Discontinuation of antiresorptive therapies: a comparison between 1998–2001 and 2002–2004 among osteoporotic women. J Clin Endocrinol Metab 92:887–894PubMedCrossRefGoogle Scholar
  141. 141.
    Blouin J, Dragomir A, Moride Y, Ste-Marie LG, Fernandes JC, Perreault S (2008) Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women. Br J Clin Pharmacol 66:117–127PubMedCrossRefGoogle Scholar
  142. 142.
    Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from two US claims databases. Mayo Clin Proc 81:1013–1022PubMedCrossRefGoogle Scholar
  143. 143.
    Clowes JA, Peel NF, Eastell R (2004) The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab 89:1117–1123PubMedCrossRefGoogle Scholar
  144. 144.
    Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB, Improving Measurements of Persistence on Actonel Treatment (IMPACT) Investigators (2007) Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 92:1296–1304PubMedCrossRefGoogle Scholar
  145. 145.
    Foged N, Delaissé J, Hou P, Lou H, Sato T, Winding B, Bonde M (1996) Quantification of the collagenolytic activity of isolated osteoclasts by enzyme-linked immunosorbent assay. J Bone Miner Res 11:226–237PubMedCrossRefGoogle Scholar
  146. 146.
    Panteghini M (2007) Traceability, reference systems and result comparability. Clin Biochem Rev 28:97–104PubMedGoogle Scholar
  147. 147.
    Müller MM (2000) Implementation of reference systems in laboratory medicine. Clin Chem 46:1907–1909PubMedGoogle Scholar
  148. 148.
    Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, Hoshino T, John GW, Kobold U, on behalf of the IFCC Working Group on HbA1c Standardization et al (2004) IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem 50:166–174PubMedCrossRefGoogle Scholar
  149. 149.
    Panteghini M, Bunk D, Christenson R, Katrukha A, Porter R, Schimmel H, Wang L, Tate J, The IFCC Working Group on Standardization of Troponin I (2008) Standardization of troponin I measurements: an update. Clin Chem Lab Med 46:1501–1506PubMedCrossRefGoogle Scholar
  150. 150.
    Stamey TA, Chen Z, Prestigiacomo AF (1998) Reference material for PSA: the IFCC standardization study. Clin Biochem 31:473–481CrossRefGoogle Scholar
  151. 151.
    Stenman U (2004) Standardization of assays for human chorionic gonadotropin. Clin Chem 50:798–800PubMedCrossRefGoogle Scholar
  152. 152.
    Thienpont LM, van Uytfanghe K, Beastall G, Faix JD, Ieiri T, Miller WG, Nelson JC, Ronin C, Ross HA, Thijssen JH, Toussaint B, for the IFCC Working Group on Standardization of Thyroid Function Tests (2010) Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 1: thyroid-stimulating hormone. Clin Chem 56:902–911PubMedCrossRefGoogle Scholar
  153. 153.
    Thienpont LM, van Uytfanghe K, De Leenheer AP (2002) Reference measurement systems in clinical chemistry. Clin Chim Acta 323:73–87PubMedCrossRefGoogle Scholar
  154. 154.
    Morris HA (2009) Traceability and standardization of immunoassays: a major challenge. Clin Biochem 42:241–245PubMedCrossRefGoogle Scholar
  155. 155.
    Panteghini M (2009) Traceability as a unique tool to improve standardization in laboratory medicine. Clin Biochem 42:236–240PubMedCrossRefGoogle Scholar
  156. 156.
    Christenson RH, Duh SH, Apple FS, Bodor GS, Bunk DM, Panteghini M, Welch MJ, Wu AHB, Kahn SE, for the American Association for Clinical Chemistry Cardiac Troponin I Standardization Committee (2006) Toward standardization of cardiac troponin I measurements part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays. Clin Chem 52:1685–1692PubMedCrossRefGoogle Scholar
  157. 157.
    Klee GG (2010) Harmonization and standardization of thyroid function tests. Clin Chem 56:879–880PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • S. Vasikaran
    • 1
    • 2
  • R. Eastell
    • 3
  • O. Bruyère
    • 4
  • A. J. Foldes
    • 5
  • P. Garnero
    • 6
  • A. Griesmacher
    • 7
  • M. McClung
    • 8
  • H. A. Morris
    • 9
  • S. Silverman
    • 10
  • T. Trenti
    • 11
  • D. A. Wahl
    • 12
  • C. Cooper
    • 13
    • 14
  • J. A. Kanis
    • 15
  • for the IOF-IFCC Bone Marker Standards Working Group
  1. 1.Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory MedicineRoyal Perth HospitalPerthAustralia
  2. 2.School of Pathology and Laboratory MedicineUniversity of Western AustraliaNedlandsAustralia
  3. 3.Centre for Biomedical ResearchNorthern General HospitalSheffieldUK
  4. 4.Department of Public Health, Epidemiology and Health EconomicsUniversity of LiègeLiègeBelgium
  5. 5.Osteoporosis CenterHadassah University HospitalJerusalemIsrael
  6. 6.INSERM Unit 664LyonFrance
  7. 7.Central Institute of Medical and Chemical Laboratory DiagnosticsUniversity Hospital of InnsbruckInnsbruckAustria
  8. 8.Oregon Osteoporosis CenterPortlandUSA
  9. 9.School of Pharmacy and Medical SciencesUniversity of South AustraliaAdelaideAustralia
  10. 10.Cedars-Sinai/University of CaliforniaLos AngelesUSA
  11. 11.Patologia Clinica, Tossicologia e Diagnostica Avanzata, Dipartimento di Patologia ClinicaOspedale Nuovo Sant’Agostino EstenseModenaItaly
  12. 12.International Osteoporosis FoundationNyonSwitzerland
  13. 13.MRC Lifecourse Epidemiology Unit, Southampton General HospitalUniversity of SouthamptonSouthamptonUK
  14. 14.NIHR Musculoskeletal Biomedical Research Unit, Institute of Musculoskeletal SciencesUniversity of OxfordOxfordUK
  15. 15.Centre for Metabolic Bone Diseases (WHO Collaborating Centre)University of Sheffield Medical SchoolSheffieldUK

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