Wiener Medizinische Wochenschrift

, Volume 162, Issue 21–22, pp 464–477 | Cite as

Biomarkers of bone turnover in diagnosis and therapy of osteoporosis

A consensus advice from an Austrian working group
  • Christian Bieglmayer
  • Hans Peter Dimai
  • Rudolf Wolfgang Gasser
  • Stefan Kudlacek
  • Barbara Obermayer-Pietsch
  • Wolfgang Woloszczuk
  • Elisabeth Zwettler
  • Andrea Griesmacher
main topic

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.

Keywords

Advice Biomarkers Bone turnover Osteoporosis 

Biomarker des Knochenumbaus in Diagnose und Therapie der Osteoporose

Leitfaden einer österreichischen Arbeitsgruppe

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.

Schlüsselwörter

Leitfaden Biomarker Knochenumbau Osteoporose 

References

  1. 1.
    Seibel MJ. Biochemical markers of bone remodelling. Endocrinol Metab Clin North Am. 2003;32:83–113.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 3.
    WHO Technical report series—assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva: WHO; 1994.Google Scholar
  4. 4.
    Kanis J, Melton L, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005;16(Suppl 2):S3–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–9.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Cauley JA, Thompson DE, Ensrud KC, et al. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11:556–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Kanis JA, Borgstrom F, De Laet C, Johansson H, et al. Assessment of fracture risk. Osteoporos Int. 2005;16:581–9.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 12.
    Anderson F, Francis R, Selby P, et al. Sex hormones and osteoporosis in men. Calcif Tissue Int. 1998;68:185–8.CrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 14.
    McFarlane X, Bhalla A, Reeves D, et al. Osteoporosis in treated adult coeliac disease. Gut. 1995;36:710–4.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Christiansen C, Baastrup PC, Transbol I. Osteopenia and dysregulation of divalent cations in lithium-treated patients. Neuropsychobiology. 1975;1:344–54.PubMedCrossRefGoogle Scholar
  19. 19.
    Zamani A, Omrani GR, Nasab MM. Lithium’s effect on bone mineral density. Bone. 2009;44:331–4.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 23.
    Rezaieyazdi Z, Falsoleiman H, Khajehdaluee M, et al. Reduced bone density in patients on long term warfarin. Int J Rheum Dis. 2009;12:130–5PubMedCrossRefGoogle Scholar
  24. 24.
    Kanis JA, Melton LJ, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1117–41.Google Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Cooper C, Atkinson E, Jacobsen S, et al. Population based study of survival following osteoporotic fractures. Am J Epidemiol. 1993;137:1001–5.PubMedGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.Google Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. 42.
    Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–7.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.CrossRefGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.CrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 51.
    Pfeilschifter J, Kann PH. Diagnostik der Osteoporose. Z Gastroenterol. 2002;40:46–56.CrossRefGoogle Scholar
  52. 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.CrossRefGoogle Scholar
  53. 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.PubMedCrossRefGoogle Scholar
  54. 54.
    Kreihuber A. Osteoporosetherapie – aktueller Datenüberblick zu Raloxifen. J Miner Stoffwechs. 2008;15:220–2.Google Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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.PubMedCrossRefGoogle Scholar
  57. 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.PubMedCrossRefGoogle Scholar
  58. 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.PubMedCrossRefGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 60.
    Christgau S, Cloos PA. Current and future applications of bone turnover markers. Clin Lab. 2003;49:439–46.PubMedGoogle Scholar
  61. 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;85:3109–15PubMedCrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 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.PubMedCrossRefGoogle Scholar
  64. 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.CrossRefGoogle Scholar
  65. 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.PubMedCrossRefGoogle Scholar
  66. 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.PubMedCrossRefGoogle Scholar
  67. 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.Google Scholar
  68. 68.
    Bieglmayer C, Clodi M, Kudlacek S. Biomarker in der Osteologie: Aktueller Stand. J Miner Stoffwechs. 2006;13:82–7.Google Scholar
  69. 69.
    Ganero P. Markers of bone turnover in prostate cancer. Cancer Treatm Rev. 2001;27:187–92.CrossRefGoogle Scholar
  70. 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.Google Scholar
  71. 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.CrossRefGoogle Scholar
  72. 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;331:45–53CrossRefGoogle Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. 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.PubMedCrossRefGoogle Scholar
  75. 75.
    Beke D, Kudlacek S, Meran JG. Klinische Relevanz von Biomarkern bei der Skelettmetastasierung von Malignomen. Wien Med Wochenschr. 2007;157:375–80.PubMedCrossRefGoogle Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. 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.PubMedCrossRefGoogle Scholar
  79. 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.PubMedCrossRefGoogle Scholar
  80. 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.PubMedCrossRefGoogle Scholar
  81. 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.PubMedGoogle Scholar
  82. 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. 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.PubMedCrossRefGoogle Scholar
  84. 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.PubMedCrossRefGoogle Scholar
  85. 85.
    Bjarnason NH, Henriksen EEG, Alexandersen P, et al. Mechanism of circadian variation in bone resorption. Bone. 2002;30:307–13.PubMedCrossRefGoogle Scholar
  86. 86.
    Schmidt-Gayk H, Roth HJ, Becker S, et al. Noninvasive parameters of bone metabolism. Curr Opin Nephrol Hypertens. 1995 Jul;4:334–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Ohishi T, Takahashi M, Kushida K, et al. Changes of biochemical markers during fracture healing. Arch Orthop Trauma Surg. 1998;118:126–30.PubMedCrossRefGoogle Scholar
  88. 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.PubMedCrossRefGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.PubMedCrossRefGoogle Scholar
  91. 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.PubMedCrossRefGoogle Scholar
  92. 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.PubMedCrossRefGoogle Scholar
  93. 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.PubMedGoogle Scholar
  94. 94.
    Bornstein P. The NH. (2)-terminal propeptides of fibrillar collagens: highly conserved domains with poorly understood functions. Matrix Biol. 2002;21:217–26.PubMedCrossRefGoogle Scholar
  95. 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.PubMedCrossRefGoogle Scholar
  96. 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.PubMedCrossRefGoogle Scholar
  97. 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.PubMedCrossRefGoogle Scholar
  98. 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.PubMedCrossRefGoogle Scholar
  99. 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.PubMedCrossRefGoogle Scholar
  100. 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.PubMedGoogle Scholar
  101. 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.PubMedGoogle Scholar
  102. 102.
    Colford J, Sailer D, Langman C. Five osteocalcin assays compared: tracer specificity, fragment interference, and calibration. Clin Chem. 1997;43:1240–1.PubMedGoogle Scholar
  103. 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.PubMedCrossRefGoogle Scholar
  104. 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.PubMedCrossRefGoogle Scholar
  105. 105.
    Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456–69.PubMedCrossRefGoogle Scholar
  106. 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.PubMedCrossRefGoogle Scholar
  107. 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.Google Scholar
  108. 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.PubMedCrossRefGoogle Scholar
  109. 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.PubMedGoogle Scholar
  110. 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. 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.PubMedCrossRefGoogle Scholar
  112. 112.
    Delmas PD, Adami S, Strugula C, et al. Intravenous Ibandronate Injections in postmenopausal women with osteoporosis. Arthritis Rheum. 2006;54:1838–46.PubMedCrossRefGoogle Scholar
  113. 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.PubMedCrossRefGoogle Scholar
  114. 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.PubMedCrossRefGoogle Scholar
  115. 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.PubMedCrossRefGoogle Scholar
  116. 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.PubMedGoogle Scholar
  117. 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.PubMedCrossRefGoogle Scholar
  118. 118.
    103 K/DOQI guidelines for the management of renal osteodystrophy. Am J Kidney Dis. 2003;42(Suppl 3):S1–201.Google Scholar
  119. 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.PubMedCrossRefGoogle Scholar
  120. 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.CrossRefGoogle Scholar
  121. 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.CrossRefGoogle Scholar
  122. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Christian Bieglmayer
    • 1
    • 2
  • Hans Peter Dimai
    • 3
  • Rudolf Wolfgang Gasser
    • 4
  • Stefan Kudlacek
    • 5
  • Barbara Obermayer-Pietsch
    • 6
  • Wolfgang Woloszczuk
    • 7
  • Elisabeth Zwettler
    • 8
  • Andrea Griesmacher
    • 9
  1. 1.ÖQUASTA (Austrian Society for Quality Assurance and Standardization of Medical Laboratory Tests)ViennaAustria
  2. 2.Department of Laboratory Medicine DiagnosticsGeneral Hospital of Vienna, Medical University of ViennaViennaAustria
  3. 3.Department of Endocrinology and MetabolismClinic for Internal Medicine, Medical University of GrazGrazAustria
  4. 4.Department of Internal Medicine IMedical University of InnsbruckInnsbruckAustria
  5. 5.Internal Medicine, Hospital of Brothers of Charity (Krankenhaus der Barmherzigen Brüder)ViennaAustria
  6. 6.Laboratory for Endocrinology and MetabolismClinic for Internal Medicine Medical University of GrazGrazAustria
  7. 7.Biomarker Design Forschungs GmbHViennaAustria
  8. 8.Ludwig Boltzmann Institute of Osteology, 1st Medical Department, Hanusch Hospital WGKK and AUVA Trauma Center MeidlingViennaAustria
  9. 9.Central Institute of Medical and Chemical Laboratory DiagnosticsUniversity Hospital InnsbruckInnsbruckAustria

Personalised recommendations