Body J J, Delmas P D
Service de Médecine, Institut J. Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Belgium.
J Clin Endocrinol Metab. 1992 Mar;74(3):471-5. doi: 10.1210/jcem.74.3.1740478.
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.
破骨细胞活性在肿瘤相关性高钙血症中增强，因此，这为评估骨吸收速率的新标志物提供了绝佳机会。我们测定了36例高钙血症癌症患者空腹尿中吡啶交联物吡啶啉（Pyr）和脱氧吡啶啉（D-Pyr）的排泄量（总血清钙均值±标准差为3.2±0.4 mmol/L，Ca2+为1.66±0.24 mmol/L）。其中32例患者在接受静脉注射双膦酸盐治疗后进行了重新评估。尿中Pyr和D-Pyr水平高于健康对照组（Pyr分别为130±62 vs. 40±19 nmol/mmol肌酐，D-Pyr分别为20±15 vs. 6±3 nmol/mmol肌酐；两者P均<0.001）。与正常均值相比，这分别代表平均升高3.3倍，而空腹尿钙和羟脯氨酸分别升高5.8倍和3.4倍。与尿钙和羟脯氨酸分别有97%和83%的病例个体值升高相比，Pyr和D-Pyr分别有83%和75%的病例个体值升高。头颈部肿瘤患者的Pyr和D-Pyr水平往往高于乳腺癌患者。尿中Pyr和D-Pyr相互相关（r = 0.72；P<0.001），且与羟脯氨酸高度相关（分别为r = 0.68和0.83；两者P均<0.001），但与尿钙相关性较差（分别为r = 0.21；P = 无显著性差异和r = 0.42；P = 0.01），表明这些标志物反映了骨吸收的不同事件。同样，双膦酸盐治疗后，尿中Pyr和D-Pyr水平分别下降了31%和50%，而羟脯氨酸下降了38%，尿钙下降了76%。治疗后D-Pyr与血清钙水平之间存在显著相关性（r = 0.43；P<0.05）。总之，我们发现高钙血症癌症患者尿中Pyr和D-Pyr的排泄量显著增加，且双膦酸盐治疗可使其充分降低。吡啶交联物的尿排泄量，尤其是D-Pyr，应有助于特异性定量骨基质吸收，并监测接受抗骨吸收药物治疗的癌症患者的骨吸收抑制情况。
