Skip to main content
Log in

Excretion of pyridinium cross-links of collagen in ovariectomized rats as urinary markers for increased bone resorption

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

Groups of 19-day-old rats were ovariectomized or were given sham operations. Measurements in urine of the pyridinium cross-links of collagen, pyridinoline and deoxypyridinoline, 7 weeks after surgery showed significantly higher amounts of cross-links relative to creatinine in the ovariectomized groups compared with the controls. Analyses before and after acid hydrolysis of the urine revealed that the increased excretion was only as free cross-link with no change in the concentrations of the bound forms. The loss of trabecular bone in the ovariectomized group was confirmed by immunocytochemical staining with antibodies to type I collagen. There were no differences between the ovariectomized and control groups in the concentrations of cross-links in the tibial bone or the articular cartilage. Measurements of free pyridinoline and deoxypyridinoline in urine therefore appear to provide a good index of the increased bone resorption induced by estrogen deficiency.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Nordin BEC (1971) Clinical significance and pathogenesis of osteoporosis. Br Med J 1:571–576

    PubMed  CAS  Google Scholar 

  2. Saphier PW, Stamp TCB, Kelsey CR, Loveridge N (1987) PTH bioactivity in osteoporosis. Bone and Mineral 3:75–83

    PubMed  CAS  Google Scholar 

  3. Stevenson JC, Allen PR, Abeyasekera G, Hill PA (1986) Osteoporosis with hip fracture: changes in calcium regulating hormones. Eur J Clin Invest 16:357–360

    PubMed  CAS  Google Scholar 

  4. MacIntyre I, Stevenson JC, Whitehead MI, Wimalawansa SJ Banks LM, Healy MJR (1988) Calcitonin for prevention of postmenopausal bone loss. Lancet i:900–902

    Article  Google Scholar 

  5. Riggs BL, Melton LJ (1983) Evidence for two distinct syndromes of involution osteoporosis. Am Med J 75:899–901

    Article  CAS  Google Scholar 

  6. Duursma SA, Bijlsma JWJ, van Paassen HC, Slootweg MC (1986) Oestrogens and bone metabolism: a hypothesis. Maturitas 8:1–6

    Article  PubMed  CAS  Google Scholar 

  7. Reeve J (1987) Bone turnover and trabecular plate survival after artificial menopause. Br Med J 295:757–760

    Article  CAS  Google Scholar 

  8. Robins SP (1982) Turnover and crosslinking of collagen. In: Weiss JB, Jayson MIV (eds) Collagen in health and disease. Churchill Livingstone, Edinburgh, pp 160–178

    Google Scholar 

  9. Christiansen C, Riis BJ, Rødbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet i:1105–1108

    Article  Google Scholar 

  10. Fujimoto D, Moriguchi T, Ishida T, Hayashi H (1978) The structure of pyridinoline, a collagen crosslink. Biochem Biophys Res Commun 84:52–57

    Article  PubMed  CAS  Google Scholar 

  11. Robins SP (1983) Crosslinking of collagen: isolation, structural characterization and glycosylation of pyridinoline. Biochem J 215:167–173

    PubMed  CAS  Google Scholar 

  12. Eyre DR, Koob TJ, Van Ness KP (1984) Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography. Anal Biochem 137:380–388

    Article  PubMed  CAS  Google Scholar 

  13. Ogawa T, Ono T, Tsuda M, Kawanishi Y (1982) A novel fluor in insoluble collagen: a crosslinking moiety in collagen molecule. Biochem Biophys Res Commun 107:1252–1257

    Article  PubMed  CAS  Google Scholar 

  14. Robins SP, Duncan A (1987) Pyridinium crosslinks of bone collagen and their location in peptides isolated from rat femur. Biochim Biophys Acta 914:233–239

    PubMed  CAS  Google Scholar 

  15. Robins SP (1982) An enzyme-linked immunoassay for the collagen crosslink pyridinoline. Biochem J 207:617–620

    PubMed  CAS  Google Scholar 

  16. Robins SP, Stewart P, Astbury C, Bird HA (1986) Measurement of the crosslinking compound, pyridinoline in urine as an index of collagen degradation. Ann Rheum Dis 45:969–973

    Article  PubMed  CAS  Google Scholar 

  17. Black D, Duncan A, Robins SP (1988) Quantitative analyses of the pyridinium crosslinks of collagen in urine using ionpaired reversed-phase high-performance liquid chromatography. Anal Biochem 169:197–203

    Article  PubMed  CAS  Google Scholar 

  18. Waynforth HB (1980) Experimental and surgical techniques in the rat. Academic Press, London, New York

    Google Scholar 

  19. Hendricks DM, Dickey JF, Hill JR (1971) Plasma estrogen and progesterone levels in cows prior to and during feeding. Endocrinology 89:1350–1355

    Article  Google Scholar 

  20. Firschein HE, Shill JP (1966) The determination of total hydroxyproline in urine and bone extracts. Anal Biochem 14:296–304

    Article  PubMed  CAS  Google Scholar 

  21. Rucklidge GJ, Riddoch GI, Robins SP (1986) Immunocytochemical staining of rat tissues with antibodies to denatured type 1 collagen: a technique for localizing areas of collagen degradation. Collagen Rel Res 6:41–49

    CAS  Google Scholar 

  22. Wronksi TJ, Lowry PL, Walsh CC, Ignaszewski LA (1985) Skeletal alterations in ovariectomized rats. Calcif Tissue Int 37:324–328

    Google Scholar 

  23. Wronski TJ, Walsh CC, Zgnaszcwski LA (1986) Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats. Bone 7:119–123

    Article  PubMed  CAS  Google Scholar 

  24. Wronski TJ, Schenck PA, Cintoon M, Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tissue Int 40:155–159

    Article  PubMed  CAS  Google Scholar 

  25. Sanada H, Shikata J, Hamamoto H, Ueba Y, Yamamuro T, Takeda T (1978) Changes in collagen crosslinking and lysyl oxidase by estrogen. Biochim Biophys Acta 541:408–413

    PubMed  CAS  Google Scholar 

  26. Shimizu K, Higuchi K, Yamamuro T, Ohtsuji T, Takeda T (1982) Increase in pyridinoline cross-linking of mouse bone collagen induced by estrogen. Experientia 38:864–866

    Article  PubMed  CAS  Google Scholar 

  27. Eyre DR, Dickson IR, Van Ness K (1988) Collagen crosslinking in human bone and articular cartilage. Age-related changes in the content of mature hydroxypyridinium residues. Biochem J 252:495–500

    PubMed  CAS  Google Scholar 

  28. Jilka RL, Hamilton JW (1985) Evidence for two pathways for stimulation of collagenolysis in bone. Calcif Tissue Int 37:300–306

    PubMed  CAS  Google Scholar 

  29. Scheven BAA, Hamilton NJ, Farquharson C, Rucklidge GJ, Robins SP (1988) Immunohistochemical localization of native and denatured collagen types I and II in fetal and adult rat long bones. Bone 9:259–266

    Article  Google Scholar 

  30. Parfitt AM, Mathews CHE, Villanueva AR, Kleerekoper M, Frame B, Rao DS (1983) Relationships between surface, volume, and thickness of iliac trabecular bone in ageing and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest 72:1396–1409

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Black, D., Farquharson, C. & Robins, S.P. Excretion of pyridinium cross-links of collagen in ovariectomized rats as urinary markers for increased bone resorption. Calcif Tissue Int 44, 343–347 (1989). https://doi.org/10.1007/BF02556315

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02556315

Key words

Navigation