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Biomarkers of bone turnover in diagnosis and therapy of osteoporosis

A consensus advice from an Austrian working group

Biomarker des Knochenumbaus in Diagnose und Therapie der Osteoporose

Leitfaden einer österreichischen Arbeitsgruppe

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Summary

Aim

Reasonable application of laboratory parameters in prevention, diagnosis, treatment and therapy monitoring of osteoporosis.

Target groups

Physicians from different specialist disciplines (general medicine, geriatrics, gynaecology, urology, internal medicine—especially endocrinology and metabolism, nephrology, laboratory medicine, rheumatology, nuclear medicine, orthopaedics, paediatrics, rehabilitation and physical medicine, radiology, social medicine, transplantation medicine, accident surgery), moreover social insurances, hospitals and self-help groups.

Background

Evaluation of aetiology of bone disorders, widening of the therapeutic spectrum for diseases of bone and knowledge on biochemical markers of bone turnover. Improvements in judging the success of therapy and in monitoring the compliance of patients. Research perspectives.

Bases

Scientific literature and guidelines, consensus meetings.

Résumé

Basic and specialized laboratory investigations are important in differentiation between primary and secondary osteoporosis for an adequate therapy. Biochemical markers of bone turnover are an additional aid in evaluation of individual fracture risk. These markers identify responders to bone therapy faster than surveillance of bone mineral density, which helps to improve patient’s compliance too. Characteristics, preanalytic precautions and applications are presented for selected markers of bone resorption and formation and for parameters regulating bone metabolism.

Zusammenfassung

Ziel

Sinnvoller Einsatz der Labordiagnostik zur Prävention, Diagnose, Therapie und Therapieüberwachung der Osteoporose.

Zielgruppe

Ärztinnen und Ärzte für Allgemeinmedizin, Geriatrie, Gynäkologie, Urologie, Innere Medizin (besonders Endokrinologie und Stoffwechsel), Nephrologie, Med. und Chem. Labordiagnostik, Onkologie, Rheumatologie, Nuklearmedizin, Orthopädie, Pädiatrie, Rehabilitation und Physikalische Medizin, Radiologie, Sozialmedizin, Transplantationsmedizin, Unfallchirurgie, sowie Sozialversicherungsanstalten, Krankenanstalten, Selbsthilfegruppen.

Hintergrund

Abklärung der Ätiologie von Knochenerkrankungen. Wachsendes Spektrum der Therapiemöglichkeiten von Knochenerkrankungen und der biochemischen Marker des Knochenstoffwechsels. Verbesserungen in der Beurteilung des Therapieerfolgs und bei der Überwachung der Compliance von Patienten. Forschungsperspektiven.

Grundlagen

Wissenschaftliche Literatur, Leitlinien und Konsens-Gespräche.

Fazit

Routine- und Spezial-Laboruntersuchungen sind für die Unterscheidung zwischen primärer und sekundärer Osteoporose und für die Wahl einer angemessenen Therapie wichtig. Biochemische Marker des Knochenumbaus sind ein zusätzliches Hilfsmittel bei der Abschätzung des individuellen Frakturrisikos. Mit diesen Markern kann ein Ansprechen auf eine knochenspezifische Therapie rascher erfasst werden als mit der Überwachung der Knochenmineraldichte, dies hilft auch die Compliance der Patienten zu verbessern. Eigenschaften, Präanalytik und Anwendung von ausgewählten Markern für Knochen- Resorption und Anbau und von Parametern, die den Knochenstoffwechsel regulieren, werden präsentiert.

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References

  1. Seibel MJ. Biochemical markers of bone remodelling. Endocrinol Metab Clin North Am. 2003;32:83–113.

    Article  PubMed  CAS  Google Scholar 

  2. Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int. 2000;11(Suppl 6):S2–17.

    Article  PubMed  Google Scholar 

  3. WHO Technical report series—assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva: WHO; 1994.

  4. Kanis J, Melton L, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–41.

    Article  PubMed  CAS  Google Scholar 

  5. Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005;16(Suppl 2):S3–7.

    Article  PubMed  Google Scholar 

  6. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–9.

    Article  PubMed  CAS  Google Scholar 

  7. Cooper C, Cole ZA, Holroyd CR, et al. and IOF CSA Working Group on Fracture Epidemiology. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int. 2011;22:1277–88.

    Article  PubMed  CAS  Google Scholar 

  8. Dimai HP, Svedbom A, Fahrleitner-Pammer A, et al. Epidemiology of hip fractures in Austria: evidence for a change in the secular trend. Osteoporos Int. 2011;22:685–92.

    Article  PubMed  CAS  Google Scholar 

  9. Cauley JA, Thompson DE, Ensrud KC, et al. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11:556–61.

    Article  PubMed  CAS  Google Scholar 

  10. Kanis JA, Borgstrom F, De Laet C, Johansson H, et al. Assessment of fracture risk. Osteoporos Int. 2005;16:581–9.

    Article  PubMed  Google Scholar 

  11. Kanis JA, Johnell O, Oden A, et al. FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19:385–97.

    Article  PubMed  CAS  Google Scholar 

  12. Anderson F, Francis R, Selby P, et al. Sex hormones and osteoporosis in men. Calcif Tissue Int. 1998;68:185–8.

    Article  Google Scholar 

  13. Ludwig H, Fritz E, Friedl H. Epidemiologic and age dependent data on multiple myeloma in Austria. J Nat Cancer Inst. 1982;68:729–33.

    PubMed  CAS  Google Scholar 

  14. McFarlane X, Bhalla A, Reeves D, et al. Osteoporosis in treated adult coeliac disease. Gut. 1995;36:710–4.

    Article  PubMed  CAS  Google Scholar 

  15. Szulc P, Delmas PD. Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int. 2008;19:1683–704.

    Article  PubMed  CAS  Google Scholar 

  16. Kanis JA, Stevenson M, McCloskey EV, Davis S, Lloyd-Jones M. Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess. 2007;11:1–231.

    Google Scholar 

  17. Takkouche B, Montes-Martinez A, Gill SS, et al. Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf. 2007;30:171–84.

    Article  PubMed  Google Scholar 

  18. Christiansen C, Baastrup PC, Transbol I. Osteopenia and dysregulation of divalent cations in lithium-treated patients. Neuropsychobiology. 1975;1:344–54.

    Article  PubMed  CAS  Google Scholar 

  19. Zamani A, Omrani GR, Nasab MM. Lithium’s effect on bone mineral density. Bone. 2009;44:331–4.

    Article  PubMed  CAS  Google Scholar 

  20. Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319–26.

    Article  PubMed  Google Scholar 

  21. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009;180:32–9.

    Article  PubMed  Google Scholar 

  22. Jamal SA, Browner WS, Bauer DC, et al. Warfarin use and risk for osteoporosis in elderly women. Study of osteoporotic fractures research group. Ann Intern Med. 1998;128:829–832.

    PubMed  CAS  Google Scholar 

  23. Rezaieyazdi Z, Falsoleiman H, Khajehdaluee M, et al. Reduced bone density in patients on long term warfarin. Int J Rheum Dis. 2009;12:130–5

    Article  PubMed  Google Scholar 

  24. Kanis JA, Melton LJ, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1117–41.

    Google Scholar 

  25. Kanis JA, Johnell O, Oden A, et al. Risk of hip fracture according to the World Health Organization criteria for osteoporosis and osteopenia. Bone. 2000;27:585–90.

    Article  PubMed  CAS  Google Scholar 

  26. Cummings S, Black D, Nevitt M. for the study of osteoporotic fractures research group. Bone density at various sites for prediction of hip fractures. Lancet. 1993;341,72–5.

    Article  PubMed  CAS  Google Scholar 

  27. Cooper C, Atkinson E, Jacobsen S, et al. Population based study of survival following osteoporotic fractures. Am J Epidemiol. 1993;137:1001–5.

    PubMed  CAS  Google Scholar 

  28. Kudlacek S, Schneider B, Resch H, et al. Die lumbale BMD – Risikofaktor für Wirbelkörperfrakturen bei der Frau. Dtsch Med Wschr. 1998;123:651–7.

    Article  PubMed  CAS  Google Scholar 

  29. Dobnig H. A review of the health consequences of the vitamin D deficiency pandemic. J Neurol Sci. 2011 Sept 21. Epub ahead of print.

  30. Sahota O, Mundey MK, San P, et al. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone. 2004;35:312–9.

    Article  PubMed  CAS  Google Scholar 

  31. Bischoff-Ferrari HA, Giovannucci E, Willett WC, et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84:18–28.

    PubMed  CAS  Google Scholar 

  32. Kudlacek S, Schneider B, Peterlik M, et al. And Austrian study group on normative values of bone metabolism. Assessment of vitamin D and calcium status in healthy adult Austrians. Eur J Clin Invest. 2003;33:323–31.

    Article  PubMed  CAS  Google Scholar 

  33. Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. 2004;116:634–9.

    Article  PubMed  CAS  Google Scholar 

  34. Garnero P, Munoz F, Sornay-Rendu E, et al. Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone. 2007;40:716–22.

    Article  PubMed  CAS  Google Scholar 

  35. Meier C, Woitge HW, Witte K, et al. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res. 2004;19:1221–30.

    Article  PubMed  CAS  Google Scholar 

  36. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257–64.

    Article  PubMed  CAS  Google Scholar 

  37. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. and Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.

    Article  PubMed  CAS  Google Scholar 

  38. Garnero P, Hausherr E, Chapuy MC, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res. 1996;11:1531–8.

    Article  PubMed  CAS  Google Scholar 

  39. Garnero P, Sornay-Rendu E, Duboeuf F, et al. Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res. 1999;14:1614–21.

    Article  PubMed  CAS  Google Scholar 

  40. Garnero P, Sornay-Rendu E, Claustrat B et al. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women. The OFELY study. J Bone Min Res. 2000;15:1526–36.

    Article  CAS  Google Scholar 

  41. Garnero P, Delmas PD. Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women. J Musculoskelet Neuronal Interact. 2004;4:50–63.

    PubMed  CAS  Google Scholar 

  42. Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–7.

    Article  PubMed  CAS  Google Scholar 

  43. Obermayer-Pietsch BM, Bonelli CM, Walter DE, et al. Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J Bone Miner Res. 2004;19:42–7.

    Article  PubMed  Google Scholar 

  44. Gugatschka M, Dobnig H, Fahrleitner-Pammer A, et al. Molecularly defined lactose malabsorption, milk consumption and anthropometric differences in adult males. Quart J Med. 2005;12:857–63.

    Article  Google Scholar 

  45. Ji GR, Yao M, Sun CY, et al. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta-analysis. J Int Med Res. 2009;37:1725–32.

    PubMed  Google Scholar 

  46. Garnero P, Sornay-Rendu E, Chapuy MC, et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996;11:337–49.

    Article  PubMed  CAS  Google Scholar 

  47. Srivastava AK Vilet EL, Lewiecki EM, et al. Clinical use of serum and urine bone markers in the management of osteoporosis. Curr Med Res Opin. 2005;21:1015–26.

    Article  PubMed  CAS  Google Scholar 

  48. Chesnut CH 3rd, Bell NH, Clark GS, et al. 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. 1997;102:29–37.

    Article  PubMed  CAS  Google Scholar 

  49. Delmas PD. The role of markers of bone turnover in the assessment of fracture risk in postmenopausal women. Osteoporosis Int. 1998;8(Suppl 1):S32–6.

    Article  Google Scholar 

  50. van Daele PL, Seibel MJ, Burger H, et al. Case-control-analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study. Brit Med J. 1996;312:482–3.

    Article  PubMed  CAS  Google Scholar 

  51. Pfeilschifter J, Kann PH. Diagnostik der Osteoporose. Z Gastroenterol. 2002;40:46–56.

    Article  Google Scholar 

  52. Stepan JJ. Clinical value of the biochemical markers of bone remodelling in the assessment of bone metabolic diseases. Jugoslov Med Biohem. 2006;25:241–8.

    Article  CAS  Google Scholar 

  53. Bauer DC, Garnero P, Hochberg MC et al. Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture Intervention trial. J Bone Miner Res. 2006;21:292–9.

    Article  PubMed  CAS  Google Scholar 

  54. Kreihuber A. Osteoporosetherapie – aktueller Datenüberblick zu Raloxifen. J Miner Stoffwechs. 2008;15:220–2.

    Google Scholar 

  55. Maricic M, Adachi JD, Sarkar S, et al. Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Arch Intern Med. 2002;162:1140–3.

    Article  PubMed  CAS  Google Scholar 

  56. Cummings SR, San Martin J, McClung MR, et al. the FREEDOM trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.

    Article  PubMed  CAS  Google Scholar 

  57. Jiang Y, Zhao JJ, Mitlak BH, et al. Recombinant human parathyroid hormone (1–34) (teriparatide) improves both cortical and cancellous bone structure. J Bone Miner Res. 2003;18:1932–41.

    Article  PubMed  CAS  Google Scholar 

  58. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–41.

    Article  PubMed  CAS  Google Scholar 

  59. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350:459–68.

    Article  PubMed  CAS  Google Scholar 

  60. Christgau S, Cloos PA. Current and future applications of bone turnover markers. Clin Lab. 2003;49:439–46.

    PubMed  CAS  Google Scholar 

  61. Tonino RP, Meunier PJ, Emkey R, et al. Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. J Clin Endocrinol Metab. 2000;85:3109–15

    Article  PubMed  CAS  Google Scholar 

  62. Hochberg MC, Greenspan S, Wasnich RD, et al. 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. 2002;87:1586–92.

    Article  PubMed  CAS  Google Scholar 

  63. Bergmann P, Body JJ, Boonen S, et al. and Members of Advisory Board on Bone Markers. 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  PubMed  CAS  Google Scholar 

  64. Bauer DC, Garnero P, Bilezikian JP, et al. Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis. J Clin Endocrin Metab. 2006;91:1370–9.

    Article  CAS  Google Scholar 

  65. Dobnig H, Sipos A, Jiang Y, et al. Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy. J Clin Endocrinol Metab. 2005;90:3970–7.

    Article  PubMed  CAS  Google Scholar 

  66. Black DM, Greenspan SL, Ensrud KE, et al. and PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003;349:1207–15.

    Article  PubMed  CAS  Google Scholar 

  67. H, Cosman F, Endres DB, et al. Application of biochemical markers of bone turnover in the assessment and monitoring of bone diseases; Approved Guideline. In: NCCLS document C48-A (ISBN 1-56238-539-9) 2004; 24 (22). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087–1898 USA.

  68. Bieglmayer C, Clodi M, Kudlacek S. Biomarker in der Osteologie: Aktueller Stand. J Miner Stoffwechs. 2006;13:82–7.

    Google Scholar 

  69. Ganero P. Markers of bone turnover in prostate cancer. Cancer Treatm Rev. 2001;27:187–92.

    Article  Google Scholar 

  70. Jung K, Lein M, Stephan C, et al. Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. In J Ca. 2004;111:783–91.

    CAS  Google Scholar 

  71. Brown JE, Thomson CS, Ellis SP, et al. Bone resorption predicts for skeletal complications in metastatic bone disease. Brit J Ca. 2003;89:2031–37.

    Article  CAS  Google Scholar 

  72. de la Piedra C, Castro-Errecaborde NA, Traba ML, et al. Bone remodelling markers in the detection of bone metastases in prostate cancer. Clin Chem Acta. 2003;331:45–53

    Article  CAS  Google Scholar 

  73. Koizumi M, Takahashi S, Ogata E. Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer. Breast Cancer. 2003;10:21–7.

    Article  PubMed  Google Scholar 

  74. Brasso K, Christensen IJ, Johansen JS, et al. Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006;66:503–13.

    Article  PubMed  CAS  Google Scholar 

  75. Beke D, Kudlacek S, Meran JG. Klinische Relevanz von Biomarkern bei der Skelettmetastasierung von Malignomen. Wien Med Wochenschr. 2007;157:375–80.

    Article  PubMed  Google Scholar 

  76. Lipton A, Cook R, Saad F, et al. Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer. 2008;113:193–201.

    Article  PubMed  CAS  Google Scholar 

  77. Lipton A, Chapman JA, Demers L, et al. Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: results of NCIC CTG MA.14. J Clin Oncol. 2011;29:3605–10.

    Article  PubMed  Google Scholar 

  78. Naylor KE, Iqbal P, Fledelius C, et al. The effect of pregnancy on bone density and bone turnover. J Bone Miner Res. 2000;15:129–37.

    Article  PubMed  CAS  Google Scholar 

  79. Woitge HW, Friedmann B, Suttner S, et al. Changes in bone turnover induced by aerobic and anaerobic exercise in young males. J Bone Miner Res. 1998;13:1797–1804.

    Article  PubMed  CAS  Google Scholar 

  80. Maïmoun L, Manetta J, Couret I, et al. The intensity level of physical exercise and the bone metabolism response. Int J Sports Med. 2006;27:105–111.

    Article  PubMed  CAS  Google Scholar 

  81. Huber F, Traber L, Roth HJ, et al. Markers of bone resorption—measurement in serum, plasma or urine? Clin Lab. 2003;49:203–7.

    PubMed  CAS  Google Scholar 

  82. Schmidt-Gayk H, Huber F, Traber L, et al. Vitamin-D-Versorgung und Marker des Knochenabbaus (b-CrossLaps) bei prä- und postmenopausalen Frauen. Osteoporose Rheuma aktuell. 2003;4:36–42.

    Google Scholar 

  83. Garnero P, Mulleman D, Munoz F, et al. Long-term variability of markers of bone turnover in postmenopausal women and implications for their clinical use: the OFELY study. J Bone Miner Res. 2003;18:1789–94.

    Article  PubMed  Google Scholar 

  84. Christgau S, Bitsch-Jensen O, Hanover Bjarnason N, et al. Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy. Bone. 2000;26:505–11.

    Article  PubMed  CAS  Google Scholar 

  85. Bjarnason NH, Henriksen EEG, Alexandersen P, et al. Mechanism of circadian variation in bone resorption. Bone. 2002;30:307–13.

    Article  PubMed  CAS  Google Scholar 

  86. Schmidt-Gayk H, Roth HJ, Becker S, et al. Noninvasive parameters of bone metabolism. Curr Opin Nephrol Hypertens. 1995 Jul;4:334–8.

    Article  PubMed  CAS  Google Scholar 

  87. Ohishi T, Takahashi M, Kushida K, et al. Changes of biochemical markers during fracture healing. Arch Orthop Trauma Surg. 1998;118:126–30.

    Article  PubMed  CAS  Google Scholar 

  88. Ingle BM, Hay SM, Bottjer HM, et al. Changes in bone mass and bone turnover following distal forearm fracture. Osteoporos Int. 1999;10:399–407.

    Article  PubMed  CAS  Google Scholar 

  89. Akesson K, Käkönen SM, Josefsson PO, et al. Fracture-induced changes in bone turnover: a potential confounder in the use of biochemical markers in osteoporosis. J Bone Miner Metab. 2005;23:30–5.

    Article  PubMed  CAS  Google Scholar 

  90. Veitch SW, Findlay SC, Hamer AJ, et al. Changes in bone mass and bone turnover following tibial shaft fracture. Osteoporos Int. 2006;17:364–72.

    Article  PubMed  CAS  Google Scholar 

  91. Garnero P, Delmas PD. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab. 1993;77:1046–53.

    Article  PubMed  CAS  Google Scholar 

  92. Alvarez L, Guañabens N, Peris P, et al. Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget’s disease. Bone 2001;29:447–52.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  94. Bornstein P. The NH. (2)-terminal propeptides of fibrillar collagens: highly conserved domains with poorly understood functions. Matrix Biol. 2002;21:217–26.

    Article  PubMed  CAS  Google Scholar 

  95. Tahtela R, Seppanen J, Laitinen K, et al. Serum tartrate-resistant acid phosphatase 5b in monitoring bisphosphonate treatment with clodronate: a comparison with urinary N-terminal telopeptide of type I collagen and serum type I procollagen amino-terminal propeptide. Osteoporos Int. 2005;16:1109–16.

    Article  PubMed  CAS  Google Scholar 

  96. Chen P, Satterwhite JH, Licata AA, et al. Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res. 2005;20:962–70.

    Article  PubMed  CAS  Google Scholar 

  97. Schytte S, Hansen M, Moller S, et al. Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis. Scand J Clin Lab Invest. 1999;59:627–34.

    Article  PubMed  CAS  Google Scholar 

  98. Hellman J, Kakonen SM, Matikainen MT, et al. Epitope mapping of nine monoclonal antibodies against osteocalcin: combinations into two-site assays affect both assay specificity and sample stability. J Bone Miner Res. 1996;11:1165–75.

    Article  PubMed  CAS  Google Scholar 

  99. Takahashi M, Kushida K, Nagano A, et al. Comparison of the analytical and clinical performance characteristics of an N-MID versus an intact osteocalcin immunoradiometric assay. Clin Chim Acta. 2000;294:67–76.

    Article  PubMed  CAS  Google Scholar 

  100. Durham BH, Robinson J, Fraser WD. Differences in the stability of intact osteocalcin in serum, lithium heparin plasma and EDTA plasma. Ann Clin Biochem. 1995;32:422–3.

    PubMed  Google Scholar 

  101. Noonan K, Kalu ME, Holownia P, et al. Effect of different storage temperatures, sample collection procedures and immunoassay methods on osteocalcin measurement. Eur J Clin Chem Clin Biochem. 1996;34:841–4.

    PubMed  CAS  Google Scholar 

  102. Colford J, Sailer D, Langman C. Five osteocalcin assays compared: tracer specificity, fragment interference, and calibration. Clin Chem. 1997;43:1240–1.

    PubMed  CAS  Google Scholar 

  103. Vergnaud P, Garnero P, Meunier PJ, 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.

    Article  PubMed  CAS  Google Scholar 

  104. Holzer G, Grasse AV, Zehetmayer S, et al. Vitamin K epoxide reductase (VKORC1) gene mutations in osteoporosis: a pilot study. Transl Res. 2010;156:37–44.

    Article  PubMed  CAS  Google Scholar 

  105. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.

    Article  PubMed  CAS  Google Scholar 

  106. Fernández-Real JM, Izquierdo M, Ortega F, et al. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab. 2009;94:237–45.

    Article  PubMed  CAS  Google Scholar 

  107. Iki M, Tamaki J, Fujita Y, et al. Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo osteoporosis risk in men (FORMEN) Study. Osteoporos Int. 2011 Mar 25. Epub ahead of print.

  108. Bonde M, Qvist P, Fledelius C, et al. Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab. 1995;80:864–8.

    Article  PubMed  CAS  Google Scholar 

  109. Christgau S, Rosenquist C, Alexandersen P, et al. Clinical evaluation of the serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products from type I collagen C-telopetides. Clin Chem. 1998;44:2290–300.

    PubMed  CAS  Google Scholar 

  110. Ganero P, Borel O, Delmas PD. Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin Chem. 2001;47:694–702.

    Google Scholar 

  111. Ravn P, Clemmesen B, Riis BJ, et al. The effect on bone mass and bone markers of different doses of Ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis. A 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone 1996;19:527–33.

    Article  PubMed  CAS  Google Scholar 

  112. Delmas PD, Adami S, Strugula C, et al. Intravenous Ibandronate Injections in postmenopausal women with osteoporosis. Arthritis Rheum. 2006;54:1838–46.

    Article  PubMed  CAS  Google Scholar 

  113. Reginster J-Y, Adami S, Lakatos P, et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis. 2006;65:654–61.

    Article  PubMed  CAS  Google Scholar 

  114. Halleen JM, Raisanen S, Salo JJ, et al. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase. J Biol Chem. 1999;274:22907–10.

    Article  PubMed  CAS  Google Scholar 

  115. Janckila AJ, Nakasato YR, Neustadt DH, et al. Disease-specific expression of tartrate-resistant acid phosphatase isoforms. J Bone Miner Res. 2003;18:1916–9.

    Article  PubMed  CAS  Google Scholar 

  116. Halleen JM, Alatalo SL, Janckila AJ, et al. Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption. Clin Chem. 2001;47:597–600.

    PubMed  CAS  Google Scholar 

  117. Hannon RA, Clowes JA, Eagleton AC, et al. Clinical performance of immunoreactive tartrate-resistant acid phosphatase isoform 5b as a marker of bone resorption. Bone 2004;34:187–94.

    Article  PubMed  CAS  Google Scholar 

  118. 103 K/DOQI guidelines for the management of renal osteodystrophy. Am J Kidney Dis. 2003;42(Suppl 3):S1–201.

    Google Scholar 

  119. Souberbielle J-C, Boutten A, Carlier M-C, et al. Inter-method variability in PTH measurement: implication for the care of CKD patients. Kidney Int. 2006;70:345–50.

    Article  PubMed  CAS  Google Scholar 

  120. Woitge HW, Knothe A, Witte K, et al. Circannual rhythmus and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study. JBMR. 2000;15:2443–50.

    Article  CAS  Google Scholar 

  121. Dawson-Hughes B, Mithal A, Bonjour JP, et al. IOF position statement: vitamin D recommendations for older adults. Osteporos Int. 2010;21:1151–4.

    Article  CAS  Google Scholar 

  122. Ross AC, Manson JE, Abrams SA, et al. The 2011 Report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. ÖQUASTA (Austrian Society for Quality Assurance and Standardization of Medical Laboratory Tests), 1090 Hörlgasse 18/5, Vienna, Austria

    Christian Bieglmayer Ph.D.

  2. Department of Laboratory Medicine Diagnostics, General Hospital of Vienna, Medical University of Vienna, 1090 Währinger Gürtel 18-20, Vienna, Austria

    Christian Bieglmayer Ph.D.

  3. Department of Endocrinology and Metabolism, Clinic for Internal Medicine, Medical University of Graz, Graz, Austria

    Hans Peter Dimai M.D.

  4. Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria

    Rudolf Wolfgang Gasser M.D.

  5. Internal Medicine, Hospital of Brothers of Charity (Krankenhaus der Barmherzigen Brüder), Vienna, Austria

    Stefan Kudlacek M.D.

  6. Laboratory for Endocrinology and Metabolism, Clinic for Internal Medicine Medical University of Graz, Graz, Austria

    Barbara Obermayer-Pietsch M.D.

  7. Biomarker Design Forschungs GmbH, Vienna, Austria

    Wolfgang Woloszczuk Ph.D.

  8. Ludwig Boltzmann Institute of Osteology, 1st Medical Department, Hanusch Hospital WGKK and AUVA Trauma Center Meidling, Vienna, Austria

    Elisabeth Zwettler M.D.

  9. Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Innsbruck, Innsbruck, Austria

    Andrea Griesmacher M.D.

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  1. Christian Bieglmayer Ph.D.
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  2. Hans Peter Dimai M.D.
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  3. Rudolf Wolfgang Gasser M.D.
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  4. Stefan Kudlacek M.D.
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  5. Barbara Obermayer-Pietsch M.D.
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  6. Wolfgang Woloszczuk Ph.D.
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  7. Elisabeth Zwettler M.D.
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  8. Andrea Griesmacher M.D.
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Corresponding author

Correspondence to Christian Bieglmayer Ph.D..

Additional information

In grateful remembrance of Prof. Heinrich Schmidt-Gayk, who supplied our working group with valuable contributions.

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Bieglmayer, C., Dimai, H., Gasser, R. et al. Biomarkers of bone turnover in diagnosis and therapy of osteoporosis. Wien Med Wochenschr 162, 464–477 (2012). https://doi.org/10.1007/s10354-012-0133-9

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  • DOI: https://doi.org/10.1007/s10354-012-0133-9

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