Miyamoto K K, McSherry S A, Robins S P, Besterman J M, Mohler J L
Department of Surgery, University of North Carolina at Chapel Hill 27599-7235.
J Urol. 1994 Apr;151(4):909-13. doi: 10.1016/s0022-5347(17)35120-0.
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.
放射性核素骨扫描监测骨转移活性的疗效仍存在争议。客观测量骨肿瘤负荷对于评估前列腺癌转移的新疗法将很有用。最近通过高压液相色谱法发现，尿中吡啶啉（在软骨和骨中发现的成熟胶原交联物）和脱氧吡啶啉（骨特异性胶原交联物）的排泄为类风湿性关节炎、骨质疏松症和代谢性骨病中的软骨和骨破坏提供了敏感的特异性指标。我们比较了27例良性前列腺增生患者（患者年龄70.0±8.5岁，标准差）、29例临床局限型前列腺癌患者（年龄70.2±9.7岁）和26例前列腺癌伴骨转移患者（年龄71.1±7.7岁）尿中脱氧吡啶啉、吡啶啉和羟脯氨酸相对于尿肌酐（nmol./mmol肌酐）的排泄情况。在5例骨转移患者中未检测到脱氧吡啶啉或吡啶啉尿排泄的昼夜变化。与良性前列腺增生患者（Mann-Whitney-Wilcoxon秩和分析，p分别<0.00004和0.002）或局限性前列腺癌患者（Mann-Whitney-Wilcoxon，p分别<0.00001和0.00005）相比，前列腺癌转移患者的吡啶啉和脱氧吡啶啉尿排泄显著更高。尿羟脯氨酸水平未能区分这3组患者。前列腺癌骨转移患者的吡啶啉和脱氧吡啶啉排泄与骨扫描索洛韦评分直接相关（r = 0.55，p<0.005和r = 0.57，p<0.004），而血清前列腺特异性抗原则无相关性（r = 0.36，p = 0.08）。在3例经骨扫描发现有新的转移病灶记录临床进展的患者中，吡啶啉和脱氧吡啶啉的系列测量值逐渐升高。测量吡啶啉和脱氧吡啶啉排泄不能诊断转移性疾病。然而，这些标志物应进一步评估用于骨转移的定量评估。
