The collagen crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), were recently identified as potential markers of the rate of bone resorption. To determine whether urinary concentrations of Pyr and D-Pyr might provide an early warning of bone metastases in patients being monitored for cancer of the prostate, we compared these two newer parameters with the conventional indicators, that is, the serum concentrations of Bone Gla protein (BGP: osteocalcin) and alkaline phosphatase (ALP), in patients with prostate cancer with and without bone metastases vs. those of age-matched patients with benign prostatic hyperplasia (BPH). Urinary excretion of these compounds, expressed as a ratio to urinary creatinine (mg/dl), was determined by high performance liquid chromatography (HPLC) in 23 patients with prostate cancer (16 with bone metastases and 7 without bone metastases) and in 23 patients with BPH. The mean values of urinary Pyr and D-Pyr; 65.02 +/- 38.16 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine, respectively, for patients with bone metastases of prostate cancer were significantly higher than those for patients without bone metastases of prostate cancer (27.43 +/- 10.29 pmol/mumol of creatinine and 4.24 +/- 1.88 pmol/mumol of creatinine) or for patients with BPH (25.58 +/- 7.54 pmol/mumol of creatinine and 3.52 +/- 1.07 pmol/mumol of creatinine). Among these three groups of patients, there were statistically significant (Pyr: P = 0.0001, D-Pyr: P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)