Collagen Cross-Link Metabolites in Urine as Markers of Bone Metastases in Prostatic Carcinoma

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Abstract
The efficacy of radionuclide bone scans in monitoring metastatic bone activity remains controversial. Objective measurement of bone tumor burden would be useful for the evaluation of new therapies for metastatic carcinoma of the prostate. The recent discovery of the urinary excretion of pyridinoline (cross-link of mature collagen found in cartilage and bone) and deoxypyridinoline (collagen cross-link specific to bone) measured by high pressure liquid chromatography has provided sensitive specific indexes of cartilage and bone breakdown in rheumatoid arthritis, osteoporosis and metabolic bone diseases. We compared the urinary excretion of deoxypyridinoline,pyridinoline and hydroxyproline relative to urinary creatinine (nmol./mmol.creatinine) in 27 patients with benign prostatic hyperplasia (patient age 70.0 +/- 8.5 years, standard deviation), 29 with clinically confined prostate cancer (age 70.2 +/- 9.7 years), and 26 with prostate cancer and bone metastases (age 71.1 +/- 7.7 years). No diurnal variation of deoxypyridinoline or pyridinoline urinary excretion was detected in 5 patients with metastases. Urinary excretion of pyridinoline and deoxypyridinoline was significantly greater in patients with metastatic carcinoma of the prostate compared with patients with either benign prostatic hyperplasia (Mann-Whitney-Wilcoxon rank sum analysis, p < 0.00004 and 0.002, respectively) or localized prostate cancer (Mann-Whitney-Wilcoxon, p < 0.00001 and 0.00005, respectively). Urinary hydroxyproline levels failed to separate the 3 groups. Pyridinoline and deoxypyridinoline excretion in prostate cancer patients with metastases directly correlated with bone scan Soloway scores (r = 0.55, p < 0.005 and r = 0.57, p < 0.004 respectively), whereas serum prostate specific antigen did not (r = 0.36, p = 0.08). Serial measurements of pyridinoline and deoxypyridinoline progressively increased in 3 patients with clinical progression documented by new metastatic lesions by bone scan. Measurement of pyridinoline and deoxypyridinoline excretion cannot diagnose metastatic disease. However, these markers should be evaluated further for quantitative assessment of bone metastases.

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