Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia.
Osteoclastic activity is increased in tumor-associated hypercalcemia, which, thus, constitutes an excellent opportunity to assess new markers of the bone resorption rate. We have measured the fasting urinary excretion of the pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) in 36 hypercalcemic cancer patients (mean +/- SD, 3.2 +/- 0.4 mmol/L for total serum Ca and 1.66 +/- 0.24 mmol/L for Ca2+). Thirty-two of them were reevaluated after treatment with iv bisphosphonates. Urinary Pyr and D-Pyr levels were higher than those in healthy controls (130 +/- 62 vs. 40 +/- 19 nmol/mmol creatinine for Pyr and 20 +/- 15 vs. 6 +/- 3 nmol/mmol creatinine for D-Pyr; P less than 0.001 for both). This represented a mean 3.3-fold increase over the normal mean compared to 5.8- and 3.4-fold increases for fasting urinary Ca and hydroxyproline, respectively. Individual values were elevated in 83% and 75% of the cases for Pyr and D-Pyr compared to 97% and 83% for urinary Ca and hydroxyproline, respectively. The levels of Pyr and D-Pyr tended to be higher in patients with head and neck tumors than in patients with breast cancer. Urinary Pyr and D-Pyr correlated with each other (r = 0.72; P less than 0.001) and were highly correlated with hydroxyproline (r = 0.68 and 0.83, respectively; P less than 0.001 for both), but poorly correlated with urinary Ca (r = 0.21; P = NS and r = 0.42; P = 0.01, respectively), suggesting that these markers reflect different events of bone resorption. Similarly, after bisphosphonate therapy, urinary Pyr and D-Pyr levels fell by 31% and 50%, respectively, compared to 38% for hydroxyproline and 76% for urinary Ca. There was a significant correlation between posttreatment D-Pyr and serum Ca levels (r = 0.43; P less than 0.05). In summary, we found that the urinary excretion of Pyr and D-Pyr was markedly increased in hypercalcemic cancer patients and was adequately lowered by bisphosphonate therapy. The urinary excretion of the pyridinium cross-links, especially D-Pyr, should be helpful to specifically quantitate bone matrix resorption and monitor the inhibition of bone resorption in cancer patients receiving antiosteolytic drugs.
Body
J J
JJ
Service de Médecine, Institut J. Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Belgium.
Delmas
P D
PD
D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001862:Bone Resorption / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D001943:Breast Neoplasms / Q000503:physiopathology; D002118:Calcium / Q000097:blood; D005260:Female; D006258:Head and Neck Neoplasms / Q000503:physiopathology; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000503:physiopathology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology* / Q000652:urine; D063065:Organophosphonates / Q000627:therapeutic use
D000596:Amino Acids; D015415:Biomarkers; D063065:Organophosphonates; C015484:pyridinoline; C036020:deoxypyridinoline; D002118:Calcium