Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 May;65(5):766–768. doi: 10.1038/bjc.1992.161

Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease.

R E Coleman 1, S Houston 1, I James 1, A Rodger 1, R D Rubens 1, R C Leonard 1, J Ford 1
PMCID: PMC1977378  PMID: 1586605

Abstract

The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beardsworth L. J., Eyre D. R., Dickson I. R. Changes with age in the urinary excretion of lysyl- and hydroxylysylpyridinoline, two new markers of bone collagen turnover. J Bone Miner Res. 1990 Jul;5(7):671–676. doi: 10.1002/jbmr.5650050702. [DOI] [PubMed] [Google Scholar]
  2. Black D., Duncan A., Robins S. P. Quantitative analysis of the pyridinium crosslinks of collagen in urine using ion-paired reversed-phase high-performance liquid chromatography. Anal Biochem. 1988 Feb 15;169(1):197–203. doi: 10.1016/0003-2697(88)90274-6. [DOI] [PubMed] [Google Scholar]
  3. Blomqvist C., Elomaa I., Virkkunen P., Porkka L., Karonen S. L., Risteli L., Risteli J. The response evaluation of bone metastases in mammary carcinoma. The value of radiology, scintigraphy, and biochemical markers of bone metabolism. Cancer. 1987 Dec 15;60(12):2907–2912. doi: 10.1002/1097-0142(19871215)60:12<2907::aid-cncr2820601211>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  4. Campbell F. C., Blamey R. W., Woolfson A. M., Elston C. W., Hosking D. J. Calcium excretion (CaE) in metastatic breast cancer. Br J Surg. 1983 Apr;70(4):202–204. doi: 10.1002/bjs.1800700405. [DOI] [PubMed] [Google Scholar]
  5. Coleman R. E., Woll P. J., Miles M., Scrivener W., Rubens R. D. Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Br J Cancer. 1988 Nov;58(5):621–625. doi: 10.1038/bjc.1988.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coombes R. C., Dady P., Parsons C., McCready V. R., Ford H. T., Gazet J. C., Powles T. J. Assessment of response of bone metastases to systemic treatment in patients with breast cancer. Cancer. 1983 Aug 15;52(4):610–614. doi: 10.1002/1097-0142(19830815)52:4<610::aid-cncr2820520406>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  7. Eyre D. R., Oguchi H. The hydroxypyridinium crosslinks of skeletal collagens: their measurement, properties and a proposed pathway of formation. Biochem Biophys Res Commun. 1980 Jan 29;92(2):403–410. doi: 10.1016/0006-291x(80)90347-2. [DOI] [PubMed] [Google Scholar]
  8. Fujimoto D., Suzuki M., Uchiyama A., Miyamoto S., Inoue T. Analysis of pyridinoline, a cross-linking compound of collagen fibers, in human urine. J Biochem. 1983 Oct;94(4):1133–1136. doi: 10.1093/oxfordjournals.jbchem.a134457. [DOI] [PubMed] [Google Scholar]
  9. Hortobagyi G. N., Libshitz H. I., Seabold J. E. Osseous metastases of breast cancer. Clinical, biochemical, radiographic, and scintigraphic evaluation of response to therapy. Cancer. 1984 Feb 1;53(3):577–582. doi: 10.1002/1097-0142(19840201)53:3<577::aid-cncr2820530335>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  10. James I. T., Perrett D., Thompson P. W. Rapid assay for hard tissue collagen cross-links using isocratic ion-pair reversed-phase liquid chromatography. J Chromatogr. 1990 Jan 26;525(1):43–57. doi: 10.1016/s0378-4347(00)83378-2. [DOI] [PubMed] [Google Scholar]
  11. Paterson C. R., Robins S. P., Horobin J. M., Preece P. E., Cuschieri A. Pyridinium crosslinks as markers of bone resorption in patients with breast cancer. Br J Cancer. 1991 Nov;64(5):884–886. doi: 10.1038/bjc.1991.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Peacock M., Robertson W. G., Nordin B. E. Relation between serum and urinary calcium with particular reference to parathyroid activity. Lancet. 1969 Feb 22;1(7591):384–386. doi: 10.1016/s0140-6736(69)91353-1. [DOI] [PubMed] [Google Scholar]
  13. Ralston S. H., Gallacher S. J., Patel U., Dryburgh F. J., Fraser W. D., Cowan R. A., Boyle I. T. Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia. Lancet. 1989 Nov 18;2(8673):1180–1182. doi: 10.1016/s0140-6736(89)91791-1. [DOI] [PubMed] [Google Scholar]
  14. Robins S. P. An enzyme-linked immunoassay for the collagen cross-link pyridinoline. Biochem J. 1982 Dec 1;207(3):617–620. doi: 10.1042/bj2070617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Segrest J. P. Urinary metabolites of collagen. Methods Enzymol. 1982;82(Pt A):398–410. doi: 10.1016/0076-6879(82)82075-2. [DOI] [PubMed] [Google Scholar]
  16. Uebelhart D., Gineyts E., Chapuy M. C., Delmas P. D. Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease. Bone Miner. 1990 Jan;8(1):87–96. doi: 10.1016/0169-6009(91)90143-n. [DOI] [PubMed] [Google Scholar]
  17. Uebelhart D., Schlemmer A., Johansen J. S., Gineyts E., Christiansen C., Delmas P. D. Effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross-links. J Clin Endocrinol Metab. 1991 Feb;72(2):367–373. doi: 10.1210/jcem-72-2-367. [DOI] [PubMed] [Google Scholar]
  18. van Holten-Verzantvoort A. T., Bijvoet O. L., Cleton F. J., Hermans J., Kroon H. M., Harinck H. I., Vermey P., Elte J. W., Neijt J. P., Beex L. V. Reduced morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (APD) treatment. Lancet. 1987 Oct 31;2(8566):983–985. doi: 10.1016/s0140-6736(87)92555-4. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES