Biochemical Markers and Bone

  • J.-E. B. Jensen
  • H. A. Sørensen
  • O. H. Sørensen


It is well established that a low bone mass is associated with an increased risk of osteoporotic fractures. Peak bone mass and bone loss with aging are the major determinants of osteoporosis [1]. It has not been clearly established at what age the negative bone balance starts. An accelerated loss of bone is seen immediately after the menopause, continuing for 2–8 years [2,3]. Serum and urinary levels of biochemical markers of bone turnover are increased during that period and return to premenopausal levels during hormone replacement therapy (HRT). This has been shown in groups of patients treated with HRT [4,5]. Significant suppression of biochemical markers has also been demonstrated in groups of patients treated with other antiresorptive agents such as bisphosphonates [6,7] or raloxifene [8]. The clinical usefulness of monitoring the bone markers in an individual patient is, however, less evident.


Bone Mineral Density Bone Resorption Bone Turnover Biochemical Marker Bone Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hui SL, Slemenda CW, Johnston CC, Jr. The contribution of bone loss to postmenopausal osteoporosis. Osteoporos Int 1990; 1: 30–34.PubMedCrossRefGoogle Scholar
  2. 2.
    WHO Study Group. Assessment of fracture risk and its application to screening for osteoporosis. WHO technical report series 843. Geneva: WHO, 1994.Google Scholar
  3. 3.
    Löfman O, Larsson L, Ross I, Toss G, Berglund K. Bone mineral density in normal Swedish women. Bone 1997;20:167–174.PubMedCrossRefGoogle Scholar
  4. 4.
    Christiansen C, Riis BJ. Five years with continous oestrogen/progesteron therapy: effects on calcium metabolism, lipoproteins, and bleeding pattern. Br J Obstet Gynaecol 1990;97:1087–1092.PubMedCrossRefGoogle Scholar
  5. 5.
    Fuleihan G E-H, Brown EM, Curtis K, et al. Effect of sequential and daily continuous hormone replacement therapy on indexes of mineral metabolism. Arch Intern Med 1992;152:1904–1909.CrossRefGoogle Scholar
  6. 6.
    Harris ST, Gertz BJ, Genant HK, et al. The effect of short-term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women. J Clin Endocrinol Metab 1993;76:1399–1406.PubMedCrossRefGoogle Scholar
  7. 7.
    Adami S, Baroni MC, Broggini M, et al. Treatment of postmenopausal osteoporosis with continuous daily oral alendronate in comparison with either placebo or intranasal salmon calcitonin. Osteoporos Int 1993;3 (Suppl 3):S21–S27.PubMedCrossRefGoogle Scholar
  8. 8.
    Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641–1687.PubMedCrossRefGoogle Scholar
  9. 9.
    Russell RG. The assessment of bone metabolism in vivo using biochemical approaches. Horm Metab Res 1997;29:138–144.PubMedCrossRefGoogle Scholar
  10. 10.
    Kivirikko KI, Laitinen O, Prockop DJ. Modification of a specific assay for hydrox-yproline in urine. Anal Biochem 1967;19:249–255.PubMedCrossRefGoogle Scholar
  11. 11.
    Wilson PS, Kleerekoper M, Bone H, Parfitt AM. Urinary total hydroxyproline measured by HPLC:comparison of spot and timed urine collections. Clin Chem 1990;36:388–389.PubMedGoogle Scholar
  12. 12.
    Eyre DR. The specificity of collagen cross-links as markers of bone and connective tissue degradation. Acta Orthop Scand 1995;266(Suppl):166–170.Google Scholar
  13. 13.
    Colwell A, Russell RG, Eastell R. Factors affecting the assay of urinary 3-hydroxy pyridinium crosslinks of collagen as markers of bone resorption. Eur J Clin Invest 1993;23:341–349.PubMedCrossRefGoogle Scholar
  14. 14.
    Kollerup G, Thamsborg G, Bhatia H, Sorensen H. Quantitation of urinary hydroxypyridinium cross-links from collagen by high-performance liquid chromatography. Scand J Clin Lab Invest 1992;52:657–662.PubMedCrossRefGoogle Scholar
  15. 15.
    Robins SP, Woitge H, Hesley R, Ju J, Seyedin S, Siebel MJ. Direct, enzyme-linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J Bone Miner Res 1994;9:1643–1649.PubMedCrossRefGoogle Scholar
  16. 16.
    Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 1994;79:1693–1700.PubMedCrossRefGoogle Scholar
  17. 17.
    Kamel S, Brazier M, Rogez JC, et al. Different responses of free and peptide-bound cross-links to vitamin D and calcium supplementation in elderly women with vitamin D insufficiency. J Clin Endocrinol Metab 1996;81:3717–3721.PubMedCrossRefGoogle Scholar
  18. 18.
    Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem 1993;39:635–640.PubMedGoogle Scholar
  19. 19.
    Hanson DA, Weis MAE, Bollen AM, Maslan SL, Singer FR, Eyre DR. A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res 1992;7:1251–1258.PubMedCrossRefGoogle Scholar
  20. 20.
    Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C. Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem 1994;40:2022–2025.PubMedGoogle Scholar
  21. 21.
    Gertz BJ, Clemens JD, Holland SD, Yuan W, Greenspan S. Application of a new serum assay for type I collagen cross-linked N-telopeptides: assessment of diurnal changes in bone turnover with and without alendronate treatment. Calcif Tissue Int 1998; 63:102–106.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenquist C, Fledelius C, Christgau S, et al. Serum crosslaps one step ELISA. First application of monoclonal antibodies for measurement in serum of bone-related degradation products from C-terminal telopeptides of type I collagen. Clin Chem 1998;44: 2281–2289.PubMedGoogle Scholar
  23. 23.
    Minkin C. Bone acid phosphatase rtartrate-resistant acid phosphatase as a marker of osteoclast. Calcif Tissue Int 1982;34:285–290.PubMedCrossRefGoogle Scholar
  24. 24.
    Kraenzlin M, Lau KHW, Liang L, et al. Development of an immunoassay for human osteoclastic tartrate-resistant acid phosphatase. J Clin Endocrinol Metab 1990;71: 442–451.PubMedCrossRefGoogle Scholar
  25. 25.
    Woitge HW, Seibel MJ, Ziegler R. Comparison of total and bone-specific alkaline phosphatase in patients with nonskeletal disorder or metabolic bone diseases. Clin Chem 1996;42:1796–1804.PubMedGoogle Scholar
  26. 26.
    Kyd PA, Vooght KD, Kerkhoff F, Thomas E, Fairney A. Clinical usefulness of bone alkaline ohosphatase in osteoporosis. Ann Clin Biochem 1998;35:717–725.PubMedGoogle Scholar
  27. 27.
    Garnero P, Grimaux M, Seguin P, Delmas PD. Characterization of immunoreactive forms of human osteocalcin generated in vivo and in vitro. J Bone Miner Res 1994;9:255–264.PubMedCrossRefGoogle Scholar
  28. 28.
    Blumsohn A, Hannon RA, Eastell R. Apparent instability of osteocalcin in serum as measured with different commercially available immunoassays. Clin Chem 1995;41: 318–319.PubMedGoogle Scholar
  29. 29.
    Masters PW, Jones RG, Purves DA, Cooper EH, Cooney JM. Commercial assays for serum osteocalcin give clinically discordant results. Clin Chem 1994;40:358–363.PubMedGoogle Scholar
  30. 30.
    Dessauer A. Analytical requirements for biochemical bone marker assays. Scand J Clin Lab Invest 1997;227:S84–S89.Google Scholar
  31. 31.
    Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three-year follow-up study. Bone 1996; 18:487–488.PubMedCrossRefGoogle Scholar
  32. 32.
    Gundberg CM, Nieman SD, Abrams S, Rosen H. Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab 1998;83:3258–3266.PubMedCrossRefGoogle Scholar
  33. 33.
    Ebeling PR, Peterson JM, Riggs BL. Utility of type I procollagen propeptide assays for assessing abnormalities in metabolic bone disease. J Bone Miner Res 1992;7:1243–1250.PubMedCrossRefGoogle Scholar
  34. 34.
    Nielsen HK, Brixen K, Mosekilde L. Diurnal rhythm and 24-hour integrated concentrations of serum osteocalcin in normals: Influence of age, sex, season, and smoking habits. Calcif Tissue Int 1990;47:284–290.PubMedCrossRefGoogle Scholar
  35. 35.
    Eastell R, Simmons PS, Colwell A, et al. Nyctohemeral changes in bone turnover assessed by serum bone Gla-protein concentration and urinary deoxypyridinoline excretion effects of growth and aging. Clin Science 1992;83:375–382.Google Scholar
  36. 36.
    Greenspan SL, Dresner-Pollak R, Parker RA, London D, Ferguson, L. Diurnal variation of bone mineral turnover in elderly men and women. Calcif Tissue 1997;60:419–423.CrossRefGoogle Scholar
  37. 37.
    Aoshima H, Kushida K, Takahashi M, et al. Circadian variation of urinary type I collagen crosslinked C-telopeptide and free and peptide-bound forms of pyridinium crisslinks. Bone 1998;22:73–78.PubMedCrossRefGoogle Scholar
  38. 38.
    Bollen A-M, Martin MD, Leroux BG, Eyre DR. Circadian variation in urinary excretion of bone collagen cross-links. J Bone Miner Res 1995;10:1885–1890.PubMedCrossRefGoogle Scholar
  39. 39.
    Woitge HW, Scheidt-Nave C, Kissling C, et al. Seasonal variation of biochemical indexes of bone turnover: results of a population-based study. J Clin Endocrinol Metab 1998;83:68–75.PubMedCrossRefGoogle Scholar
  40. 40.
    Nielsen HK, Brixen K, Bouillon R, Mosekilde L. Changes in biochemical markers of osteoblastic a tivity during the mentrual cycle. J Clin Endocrinol Metab 1990;70: 1431–1437.PubMedCrossRefGoogle Scholar
  41. 41.
    Seibel, MJ, Woitge H, Scheidt-Nave C, et al. Urinary hydroxyoyridinium crosslinks of collagen in population-based screening for overt vertebral osteoporosis:results of a pilot study. J Bone Miner Res 1994;9:1433–1440.PubMedCrossRefGoogle Scholar
  42. 42.
    Delmas PD, Gineyts E, Bertholin A, Garnero P, Marchand F. Immunoassay of pyridinoline crosslink excretion in normal adults and in Paget’s disease. J Bone Miner Res 1993;8:643–648.PubMedCrossRefGoogle Scholar
  43. 43.
    Tarallo P, Henny J, Fournier B, Siest G. Plasma osteocalcin: biological variations and reference limits. Scand J Clin Invest 1990;50:649–655.PubMedCrossRefGoogle Scholar
  44. 44.
    Äkesson K, Lau K-H W, Johnston P, Imperio E, Baylink DJ. Effects of short-term calcium depletion and repletion on biochemical markers of bone turnover in young adult women. J Clin Endocrinol Metab 1998;83:1921–1927.PubMedCrossRefGoogle Scholar
  45. 45.
    Gertz BJ, Shao P, Hanson DA, et al. Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine. J Bone Miner Res 1994;9:135–142.PubMedCrossRefGoogle Scholar
  46. 46.
    Schneider DL, Barret-Connor EL. Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic bone mineral density. Arch Intern Med 1997; 157:1241–1245.PubMedCrossRefGoogle Scholar
  47. 47.
    Ravn P, Fledelius C, Rosenquist C, Overgaard K, Christiansen C. High bone turnover is associated with low bone mass in both pre- and postmenopausal women. Bone 1996;19:291–298.PubMedCrossRefGoogle Scholar
  48. 48.
    Mazess RB. Body Weight predict bone density better than resorption markers. Arch Intern Med 1998;158:298–300.PubMedCrossRefGoogle Scholar
  49. 49.
    Garnero P, Sornay-Rendu E, Chapuy M-C, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996;11:337–349.PubMedCrossRefGoogle Scholar
  50. 50.
    Christiansen C, Riis BJ, Rødbro P. Prediction of rapid bone loss in postmenopausal women. Lancet 1987;1:1105–1108.PubMedCrossRefGoogle Scholar
  51. 51.
    Hansen MA, Overgaard K, Riis BJ, Christiansen C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12-year study. BMJ 1991;303:961–964.PubMedCrossRefGoogle Scholar
  52. 52.
    Falch JA, Sandvik L. Perimenopausal appendicular bone loss: a 10-year prospective study. Bone 1990;11:425–428.PubMedCrossRefGoogle Scholar
  53. 53.
    Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R. Bone density change and biochemical indices of skeletal turnover. Calcif Tissue Int 1996;58:236–243.PubMedGoogle Scholar
  54. 54.
    Keen RW, Nguyen T, Sobnack R, Perry LA, Thompson PW, Spector TD. Can biochemical markers predict bone loss at the hip and spine? A 4-year prospective study of 141 early postmenopausal women. Osteoporos Int 1996;6:399–406.PubMedCrossRefGoogle Scholar
  55. 55.
    Reginster JY, Deroisy R, Collette J, Albert A, Zegels B. Prediction of bone loss rate in healthy postmenopausal women. Calcif Tissue Int 1997;60:261–264.PubMedCrossRefGoogle Scholar
  56. 56.
    Åkesson K, Ljunghall S, Jonsson B, et al. 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 1995;10:1823–1829.PubMedCrossRefGoogle Scholar
  57. 57.
    Van Daele PLA, Seibel MJ, Burger H, et al. Case-control analysis of bone resorption markers, disability, and hip fracture risk:the Rotterdam study. BMJ 1996;312:482–483.PubMedCrossRefGoogle Scholar
  58. 58.
    Garnero P, Hausherr E, Chapuy M-C, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res 1996;11: 1531–1538.PubMedCrossRefGoogle Scholar
  59. 59.
    Hirsch L, Santora A, Kher U, Yates J, Bell N, Correa-Rotter R. Bone turnover rate does not predict BMD response to alendronate. Osteoporos Int. 1996;6 (Suppl 1):S262.CrossRefGoogle Scholar
  60. 60.
    Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB. Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial. J Bone Miner Res 1998;13:1431–1438.PubMedCrossRefGoogle Scholar
  61. 61.
    Hannon RA, Blumsohn A, Ellison JV, Peel NF, Eastell R. Long-term variability of biochemical markers of bone turnover in postmenopausal women. Bone 1998;23:S159.Google Scholar

Copyright information

© Springer-Verlag London 2000

Authors and Affiliations

  • J.-E. B. Jensen
  • H. A. Sørensen
  • O. H. Sørensen

There are no affiliations available

Personalised recommendations