The Relationship between Urinary Pyridinoline, Deoxypyridinoline and Bone Metastasis in a Rat Breast Cancer Model

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, 11 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. CONCLUSION: 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.