Skip to main content
SpringerLink
Log in

The relationship between urinary pyridinoline, deoxypyridinoline and bone metastasis in a rat breast cancer model

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

Bone metastasis from breast cancer is often recognized clinically, but there are nonetheless several difficulties in diagnosis. In this study we used an animal model of bone metastasis from breast cancer and clarified the relationship between the urinary Pyd/Cr and Dpd/Cr and the progression of bone metastasis, compared with other bone related markers: serum alkaline phosphatase bone isozyme (ALP-BI), osteocalcin, and calcium.

Methods

The evaluation of bone metastasis was assessed by histological examination of the thoracic and lumbar vertebrae. According to the histological findings 4 weeks after the tumor cell injection, 1 1 animals were retrospectively divided into 2 subgroups: (1) tumor-bearing rats with bone destruction due to bone metastasis (TBR-BD(+), n=5), (2) tumor-bearing rats without bone destruction (TBR-BD(-), n = 6). These animals were compared to age-matched controls without tumor cell injection (n=6). An additional 5 animals were sacrificed at 2 weeks after the tumor cell injection to evaluate micrometastasis to bone.

Results

The values of other markers for bone metastasis in animals with micrometastatic foci in bone marrow did not differ significantly from those of the controls. Pyd/Cr and Dpd/Cr in the TBR-BD(+) group were significantly higher than those of the TBR-BD(-) and the control group (233 + 78.3 vs 93.8±6.5, 98.5±18.7, 123.1 ±35.9 vs 67.9±6.2, 60.6±9.8, p<0.01), while there were no significant differences between TBR-BD(-) and the control.

Conclusions

Both Pyd/Cr and Dpd/Cr are correlated significantly with the volume of bone metastasis, and are useful for the diagnosis and evaluation of progression of bone metastasis compared with other markers.

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

Abbreviations

Pyd/Cr:

Pyridinoline to creatinine ratio

Dpd/Cr:

Deoxypyridinoline to creatinine ratio

References

  1. Perez DJ, Powles TJ, Milan J: Detection of breast carcinoma metastases in bone; Relative merits of X-rays and skeletal scintigraphy.Lancet ii:613–616, 1983.

    Article  Google Scholar 

  2. Suzuki S: Early diagnosis for bone metastasis of breast cancer based on bone metabolism.Fukushima J Med Sci 36:11–27, 1990.

    PubMed  CAS  Google Scholar 

  3. Moriwaki S: Histopathology of metastatic bone tumors.Jpn J Cancer Chemother 14 PART II:1680–1687, 1987.

    CAS  Google Scholar 

  4. Kurokawa K, Ohnuki T: Use of urinary hydroxyproline excretion as a tumor marker of bone metastases in prostatic cancer.Kitakantoh Igaku 39:187–199, 1989.

    Google Scholar 

  5. Frenay M, Namer M, Boublil JL,et al: Value of urinary hydroxyproline and bone isoenzyme of alkaline phosphatase in the early detection and follow-up of bone metastasis in breast cancer patients.Bull Cancer 75:533–539, 1988.

    PubMed  CAS  Google Scholar 

  6. Bettica P, Baylink DJ, Moro L: Galactosyl hydroxylysine and deoxypyridinoline; A methodological comparison.Eur J Clin Chem Clin Biochem 31:459–465, 1993.

    PubMed  CAS  Google Scholar 

  7. Beardsworth LJ, Eyre DR, Dickson IR: Changes with age in the urinary excretion of lysyl- and hydroxy-lysylpyridinoline, two new markers of bone collagen turnover.Journal of Bone and Mineral Research 5:671–676, 1990.

    Article  PubMed  CAS  Google Scholar 

  8. Uebelhart D, Gineyts E, Chapuy MC,et al: Urinary excretion of pyridinium crosslinks; A new marker of bone resorption in metabolic bone disease.Bone and Mineral 8:87–96, 1990.

    Article  PubMed  CAS  Google Scholar 

  9. Yoshimura Y, Ohnishi K, Hamamura M,et al: Automated high-performance liquid chromatographic determination of hydroxylysylpyridinoline and lysylpyridinoline in urine using a column-switching method.J Chromatog 613:43–49, 1993.

    Article  CAS  Google Scholar 

  10. Fujimoto D, Suzuki M, Uchiyama A,et al: Analysis of pyridinoline, a cross-linking compound of collagen fibers, in human urine.J Biochem 94:1133–1136, 1983.

    PubMed  CAS  Google Scholar 

  11. Uebelhart D, Gineyts E, Chapuy MC,et al: Urinary excretion of pyridinium crosslinks; A new marker of bone resorption in metabolic bone disease.Bone and Mineral 8:87–96, 1990.

    Article  PubMed  CAS  Google Scholar 

  12. Paterson CR, Robins SP, Horobin JM,et al: Pyridinium crosslinks as markers of bone resorption in patients with breast cancer.Br J Cancer 64:884–886, 1991.

    PubMed  CAS  Google Scholar 

  13. Ishii S, Kitajima M: Mechanisms of bone metastasis using an animal model.Exp Med 12:1050–1054, 1994.

    CAS  Google Scholar 

  14. Tamura H, Ishii S, Ikeda T,et al: A novel animal model for bone metastasis of breast cancer.Proceedings of American Association for Cancer Research 34:97, 1993.

    Google Scholar 

  15. Yuhki N, Hamada J, Kuzumaki N,et al: Metastatic ability and expression of c-fos oncogene in cell clones of a spontaneous rat mammary tumor.Jpn J Cancer Res (Gann) 77:9–12, 1986.

    CAS  Google Scholar 

  16. Tamura H, Ishii S, Ikeda T,et al: Therapeutic efficacy of pamidronate in combination with chemotherapy to bone metastasis of breast cancer in a rat model.Surg Oncol 5:141–147, 1996.

    Article  PubMed  CAS  Google Scholar 

  17. Sekine K, Horie H, Hata K,et al: Determination of pyridinoline and deoxypyridinoline in urine by high performance liquid chromatography with fluorometric detection.Rinsho Kagaku 21:18–25, 1992.

    CAS  Google Scholar 

  18. Galasko CSB: Mechanisms of bone destruction in the development of skeletal metastases.Nature 263:507–508, 1976.

    Article  PubMed  CAS  Google Scholar 

  19. Shevrin DH, Kukreja SC, Ghosh L,et al: Development of skeletal metastasis by human prostate cancer in athymic nude mice.Clin Exp Metastasis 5:401409, 1988.

    Google Scholar 

  20. Arguello F, Baggs RB, Franz CN: A murine model of experimental metastasis to bone and bone marrow.Cancer Res 48:6876–6881, 1988.

    PubMed  CAS  Google Scholar 

  21. Kjonniksen I, Nesland JM, Pihl A,et al: Nude rat model for studying metastasis of human tumor cells to bone and bone marrow.J Natl Cancer Inst 82:408–412, 1990.

    Article  PubMed  CAS  Google Scholar 

  22. Galasko CSB: Mechanisms of bone destruction in the development of skeletal metastases.Nature 263:507–508, 1976.

    Article  PubMed  CAS  Google Scholar 

  23. Galasko CSB: Relationship of bone destruction in skeletal metastases to osteoclast activation and prostaglandins.Nature 263:508–510, 1976.

    Article  PubMed  CAS  Google Scholar 

  24. Berrettoni BA, Carter JR: Mechanisms of cancer metastasis to bone.J Bone Joint Surg 68(A)NO. 2:308–312, 1986.

    PubMed  CAS  Google Scholar 

  25. Black D, Farquharson C, Robins SP: Excretion of pyridinium cross-links of collagen in ovariectomized rats as urinary markers for increased bone resorption.Calcif Tissue Int 44:343–347, 1989.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Haga Red Cross Hospital, Keio University, School of Medicine, Japan

    Hikaru Tamura

  2. Kawasaki City Hospital, Keio University, School of Medicine, Japan

    Seiichiro Ishii

  3. Department of Surgery, Keio University, School of Medicine, Japan

    Hikaru Tamura, Tadashi Ikeda, Kohji Enomoto & Masaki Kitajima

Authors
  1. Hikaru Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seiichiro Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tadashi Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kohji Enomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masaki Kitajima
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Tamura, H., Ishii, S., Ikeda, T. et al. The relationship between urinary pyridinoline, deoxypyridinoline and bone metastasis in a rat breast cancer model. Breast Cancer 6, 23–28 (1999). https://doi.org/10.1007/BF02966902

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02966902

Key words

Search

Navigation