Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.

OBJECTIVE: To assess serum pyridinoline (Py) and deoxypyridinoline (dPy), using a new high-performance liquid chromatography (HPLC) method, as a serum marker to determine the incidence of metastatic bone disease in an animal model and in the monitoring of patients with or without metastatic bone disease from prostate cancer and renal cell carcinoma (RCC). PATIENTS, MATERIALS AND METHODS: Female C3H/He mice (8-12 weeks old) received a subcutaneous injection of tumour-cell suspensions of serially transplanted MBT tumours. The tumour cells induced osteolysis associated with osteoclast proliferation and serum samples were evaluated for Py and dPy using HPLC. The growth of the tumour macroscopically and histologically, and the extent of bone loss assessed by radiography, were compared with the serum Py and dPy level. In the clinical study, patients with or without bone metastases from RCC (24 patients) or prostate cancer (37 patients) were monitored using the same techniques and the number and extent of bone metastases compared with serum Py and dPy levels both in these patients and in 84 healthy control subjects. RESULTS: There was a significant correlation between the bone loss evaluated by radiography and the level of serum Py in the animal model. Patients with bone metastases from RCC had higher values of Py and dPy than patients without known metastatic bone disease. The serum Py level increased in two patients as metastatic bone disease progressed. Similarly, in patients with prostate cancer, the mean level of serum Py and dPy was higher in patients with bone metastasis than in the control group, and also higher than that in patients without metastases. The serum Py and dPy levels could also distinguish patients with metastatic bone disease with and without a lytic component. CONCLUSION: Measurements of serum Py appear to provide a good index of increased bone resorption induced by experimental tumours and in patients with bone metastases from RCC and prostate cancer.

Heterocyclic analogues of quinone methide: preparation and cytotoxicity of 3-oxo-3H-pyrazolo[1,5-a]indole derivatives.

A series of 3-oxo-3H-pyrazolo[1,5-a]indole derivatives was prepared and characterized as heterocyclic analogues of quinone methide. These compounds showed some cytotoxicity to cancer cells, but were ineffective in an in vivo test against murine leukemia L1210.

Serum pyridinolines as specific markers of bone resorption in hemodialyzed patients.

Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified in uremic patients undergoing maintenance hemodialysis and in healthy subjects. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline in the hemodialyzed patients were significantly higher than those in healthy subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline decreased significantly after hemodialysis with reduction rates of about 40%. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline correlated significantly with intact parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These results indicate that serum pyridinolines, especially lysyl pyridinoline, may be used as specific biochemical markers of bone resorption in hemodialyzed patients.