Skip to main content
SpringerLink
Log in

Biochemical markers of bone turnover for the clinical investigation of osteoporosis

  • Session V: Bone And Biochemical Measurements
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

The non-invasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved by measurement of urinary hydroxyproline, urinary excretion of the pyridinium crosslinks (pyridinoline and deoxypyridinoline), and by measurement of plasma tartrate-resistant acid phosphatase activity. For the screening of bone turnover in women at the menopause, and for the assessment of the level of bone turnover in elderly women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers, so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are made to develop more convenient assays and to identify other markers of bone turnover. In future a battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize the various aspects of osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Moss DW. Alkaline phosphatase isoenzymes. Clin Chem 1082;28:2007–16.

    Google Scholar 

  2. Farley JR, Chesnut CJ, Baylink DJ. Improved method for quantitative determination of serum alkaline phosphatase of skeletal origin. Clin Chem 1981;27:2002–7.

    Google Scholar 

  3. Duda RJ, O'Brien JF, Katzmann JA, et al. Concurrent assays of circulating bone gla-protein and bone alkaline phosphatase: effects of sex, age and metabolic bone disease. J Clin Endocrinol Metab 1988;66:951–7.

    Google Scholar 

  4. Hill CS, Wolfert RL. The preparation of monoclonal antibodies which react to preferentially with human bone alkaline phosphatase and not liver alkaline phosphatase. clin Chim Acta 1986;186:315–20.

    Google Scholar 

  5. Price PA. Vitamin K-dependent bone proteins. In: Cohn DV, Martin TJ, Meunier PJ, editors. 1987:4129–26.

  6. Price PA, Williamson MK, Lothringer JW. Origin of vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. J Biol Chem 1981;256:12760–6.

    Google Scholar 

  7. Price PA, Parthemore JG, Deftos LJ. New biochemical marker for bone metabolism. J Clin Invest 1980;66878–83.

  8. Lian JB, Gundberg CM. Osteocalcin: biochemical considerations and clinical applications. Clin Orthop Rel Res 1988;226:267–91.

    Google Scholar 

  9. Delmas PD, Stenner D, Wahner HW, et al. Serum bone gla-protein increases with ageing in normal women: implications for the mechanism of age-related bone loss. J Clin Invest 1983;71:1316–21.

    Google Scholar 

  10. Gundberg C, Weinstein RS. Multiple immunoreactive forms in uremic serum. J Clin Invest 1986;77:1762–7.

    Google Scholar 

  11. Tracy RP, Andrianorivo A, Riggs BL, Mann KG. Comparison of monoclonal and polyclonal antibody-based immunoassays for osteocalcin: a study of sources of variation in assay results. J Bone Miner Res 1990;5:451–61.

    Google Scholar 

  12. Brown JP, Delmas PD, Malaval L, et al. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1984;1:1091–3.

    Google Scholar 

  13. Delmas PD, Malaval L, Arlot MD, et al. Serum bone gal-protein compared to bone histomorphometry in endocrine diseases. bone 1985;6:329–41.

    Google Scholar 

  14. Delmas PD, Demiaux B, Malaval L, et al. Serum bone gla-protein (osteocalcin) in primary hyperparathyroidism and in malignant hypercalcemia: comparison with bone histomorphometry. J Clin Invest 1986;77:985–91.

    Google Scholar 

  15. Bataille R, Delmas P, Sany J. Serum bone gla-protein in multiple myeloma. Cancer 1987;59:329–34.

    Google Scholar 

  16. Simon LS, Krane SMK. Procollagen extension peptides as markers of collagen synthesis. In: Frame B, Potts JT Jr., editors. Clinical disorders of bone and mineral metabolism. Amsterdam: Excerpta Medica, 1983:108–11.

    Google Scholar 

  17. Parfiff AM, Simon LS, Villanueva AR, et al. Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone: correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res 1987;2:427–36.

    Google Scholar 

  18. Prockop OJ, Kivirikko KI. Hydroxyproline and the metabolism of collagen. In: Gould BS, editor. Treatise on collagen, vol 2. New York: Academic Press 1968:215–246.

    Google Scholar 

  19. Prockop DJ, Kivirikko KI, Tuderman K, et al. The biosynthesis of collagen and its disorders. N Engl J Med 1979;301:13–23.

    Google Scholar 

  20. Kivirikko KI. Excretion of urinary hydroxyproline peptide in the assessment of bone collagen deposition and resorption. In: Frame B, Potts JT Jr, editors. Clinical disorders of bone and mineral metabolism. Amsterdam: Excerpta Medica, 1983:105–7.

    Google Scholar 

  21. Lowry M, Hall De, Brosnan JJ. Hydroxyproline metabolism by the rat kidney: distribution of renal enzymes of hydroxyproline catabolism and renal conversion of hydroxyproline to glycine and serine. Metabolism 1985;39:955.

    Google Scholar 

  22. Delmas PD. Biochemical markers of bone turnover for the clinical assessment of metabolic disease. Endocrinol Metab Clin North Am 1990;19.

  23. Moro L, Mucelli RSP, Gazzarrini C, et al. Urinary β-1-galactosyl-O-hydroxylysine (GH) as a marker of collagen turnover of bone. Calif Tissue Int 1988;42:87–90.

    Google Scholar 

  24. Moro L, Modricky C, Rovis L, et al. Determination of galactosyl hydroxylysine in urine as a means for the identification of osteoporotic women. Bone Miner 1988;3:271–6.

    Google Scholar 

  25. Li CY, Chuda RA, Lam WKW, et al. Acid phosphatase in human plasma. J Lab Clin Med 1973;82:446–60.

    Google Scholar 

  26. Minkin C. Bone acid phosphatase: tartrate-resistant acid phosphatase as a marker of osteoclast function. Calcif Tissue Int 1982;34:285–90.

    Google Scholar 

  27. Stepan JJ, Silinkova-Malkova E, Havrenek T, et al. Relationship of plasma tartrate-resistant acid phosphatase to the bone isoenzyme of serum alkaline phosphatase in hyperparathyroidism. Clin Chim Acta 1983;133:189–200.

    Google Scholar 

  28. Stepan JJ, Pospichal J, Presl J, et al. Bone loss and biochemical indices of bone remodelling in surgically induced postmenopausal women. Bone 1987;8:279–84.

    Google Scholar 

  29. Piedra C, Torres R, Rapado A, et al. Serum tartrate-resistant acid phosphatase and bone mineral content in postmenopausal osteoporosis. Calcif Tissue Int 1989;45:58–60.

    Google Scholar 

  30. Kraenzlin M, Lau KHW, Liang L, et al. Development of an immunoassay for human serum osteoclastic tartrate-resistant acid phosphatase. J Clin Endocrinol Metab 1990;71:442–51.

    Google Scholar 

  31. Eyre DR. Collagen crosslinking amino-acids. Methods Enzymol 1987;144:115–39.

    Google Scholar 

  32. Eyre DR, Dickson IR, Van Ness KP. Collagen cross-linking in human bone and articular cartilage: age-related changes in the content of mature hydroxypyridinium residues. Biochem J 1988;252:495–500.

    Google Scholar 

  33. Black D, Duncan A, Robins SP. Quantitative analysis of the pyridinium crosslinks of collagen in urine using ion-paired reversed-phase high-performance liquid chromatography. Anal Biochem 1988;169:197–203.

    Google Scholar 

  34. Eyre DR, Koob TJ, Van Ness KP. Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography. Anal Biochem 1984;137:380–8.

    Google Scholar 

  35. Beardsworth LJ, Eyer DR, Dickson IR. Changes with age in the urinary excretion of lysyl and hydroxylysylpyridinoline, two new markers of bone collagen turnover. J Bone Miner Res 1990;5:671–6.

    Google Scholar 

  36. Uebelhart D, Schlemmer A, Johansen J, Gineyts E, Christiansen C, Delmas PD. Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium crosslinks. J Clin Endocrinol Metab 1991;72:367–73.

    Google Scholar 

  37. Delmas PD, Schlemmer A, Gineyts E, Riis B, Christiansen C. Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis. J Bone Miner Res 1992;6:639–44.

    Google Scholar 

  38. Uebelhart D, Gineyts E, Chapuy MC, Delmas PD. Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease. Bone Miner 1990;8:87–96.

    Google Scholar 

  39. Colwell A, Eastell R, Assiri AMA, Russell RGG. Effect of diet on deoxypyrinoline excretion. In: Christiansen C, Overgaard K, editors. Osteoporosis 1990, vol 2. Copenhagen: Osteopress Aps, 1990:520–91.

    Google Scholar 

  40. Eastell R, Delmas PD, Hodgson SF, et al. Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics and biochemical markers. J Clin Endocrinol Metab 1988;67:741–48.

    Google Scholar 

  41. Johansen JS, Ris BJ, Delmas PD, et al. Plasma BGP: an indicator of spontaneous bone loss and effect of estrogen treatment in postmenopausal women. Eur J Clin Invest 1988;18:191–5.

    Google Scholar 

  42. Slemenda C, Hui SL, Longcope C, et al. Sex steroids and bone mass: a study of changes about the time of menopause. J Clin Invest 1987;80:1261–69.

    Google Scholar 

  43. Brown JP, Delmas PD, Arlot M, et al. Active bone turnover of the corticoendosteal envelope in postmenopausal osteoporosis. J Clin Endocrinol Metab 1987;64:954–9.

    Google Scholar 

  44. Podenphant J, Johansen JS, Thomsen K, et al. Bone turnover in spinal osteoporosis. J Bone Miner Res 1987 2:497–503.

    Google Scholar 

  45. Civitelli R, Gonnelli S, Zacchei F, et al. Bone turnover in postmenopausal osteoporosis: effect of calcitonin treatment. J Clin Invest 1988;82:1268–74.

    Google Scholar 

  46. Eastell R, Colwell A, Assiri AMA, et al. Prediction of response to estrogen therapy using urine deoxypyridinoline. J Bone Miner Res 1990;5:S275.

    Google Scholar 

  47. Reid IR, Chapman GE, Fraser TRC, et al. Low serum osteocalcin levels in glucocorticoid-treated asthmatics. J Clin Endocrinol Metab 1986;2:379–83.

    Google Scholar 

  48. Garrel DR, Delmas PD, Welsh C, et al. Effect of moderate physical training on prednisone-induced protein wasting: a study of whole bone and bone protein metabolism. Metabolism 1988;37:257–62.

    Google Scholar 

  49. Delmi M, Rapin CH, Benoga JM, et al. Dietary supplementation in elderly patients with fractured neck of femur. Lancet 1990;335:1013–16.

    Google Scholar 

  50. Akesson K, Vergnaud P, Gineyts E, et al. Biochemical evidence for decreased one formation and increased bone resorption in women with hip fracture. In: Christiansen C, Overgaard K, editors. Osteoporosis, vol. 1. Copenhagen: Osteopress Aps, 1990:362–3.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U 234 and University C. Bernard, Hôpital E. Herriot, Lyon, France

    P. D. Delmas

Authors
  1. P. D. Delmas
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delmas, P.D. Biochemical markers of bone turnover for the clinical investigation of osteoporosis. Osteoporosis Int 3 (Suppl 1), 81–86 (1993). https://doi.org/10.1007/BF01621873

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01621873

Keywords

Search

Navigation