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.