尿I型胶原氨基末端肽辅助骨显像诊断恶性肿瘤骨转移的价值

Ancillary value of urinary N-terminal telopeptide of type I collagen to bone scintigraphy in the diag nosis of bone metastases

目的探讨应用尿I型胶原氨基末端肽（uNTX）辅助骨显像诊断恶性肿瘤骨转移的价值。方法选取227例骨显像诊断为可疑骨转移患者，首先测定患者的uNTX，并以其正常参考值上限65nmo]骨胶原当量（BCE）／mmol肌酐（Cr）作为辅助诊断骨转移的临界点：当uNTX〉65nmolBCE／mmolCr判断为骨转移，反之为非骨转移。同时综合CT、MRI、PET／CT等检查进行骨转移的确诊。应用单样本或两样本t检验比较组间uNTX差异；利用ROC曲线对uNTX辅助骨显像诊断骨转移的效能进行评价，确立实验诊断的最佳切点值，并以其为甄别骨转移的标准进行回顾性评价，计算诊断效能。结果227例患者的uNTX为（84．30±13．29）nmolBCE／mmolCr，高于正常参考值上限65nmolBCE／mmolCr（t=21．875．P〈O．01）。UNTX〉65nmolBCE／mmolCr者197例，其中188例由综合检查诊断法确诊为骨转移；UNTX〈65nmolBCE／mmolCr者共30例，其中27例由综合检查诊断法确诊非骨转移。综合检查诊断法确诊为骨转移（191例）与非骨转移（36例）患者的uNTX分别为（88．73±8．37）和（60．76±9．14）nmolBCE／mmolCr（t=-18．134，P〈O．01）。UNTX值辅助骨显像诊断骨转移的灵敏度、特异性、阳性预测值、阴性预测值、准确性、约登指数分别为98．4％（188／191）、75．0％（27／36）、95．4％（188／197）、90．0％（27／30）、94．7％（215／227）、73．4％，曲线下面积0．982；通过ROC曲线确立最佳切点值为78．88nmolBCE／mmolCr，以此切点值为甄别骨转移的界值进行回顾性评价：灵敏度、特异性、阳性预测值、阴性预测值、准确性、约登指数分别为97．4％（186／191）、94．4％（34／36）、98．9％（186／188）、87．2％（34／39）、96．9％（220／227）、91．8％。结论该研究获得的uNTX最佳切点值可以对骨显像中的疑似骨转移病例进行有效甄别，具有较高的临床应用价值。

Objective To explore the value of urinary N-terminal telopeptide of type I collagen （uNTX） combined with bone scintigraphy （BS） for the diagnosis of bone metastases. Methods A total of 227 patients suspected of bone metastases by BS were selected from Jan to May of 2012. UNTX was tested for each subject. The threshold of uNTX was chosen as 65 nmol bone collagen equivalents （BCE）/mmol creatinine （Cr） for the diagnosis of bone metastasis. Patients with uNTX greater than 65 nmol BCE/mmol Cr would be diagnosed as having bone metastasis. Other examinations （CT, MRI, PET/CT or bone biopsy） were also performed to confirm the diagnosis. The uNTX values of benign and malignant bone lesions were compared using two-sample t test. The diagnostic efficacy of uNTX combined with BS was evaluated. A ROC curve was analyzed to evaluate the cut-off value of uNTX for the diagnosis of bone metastasis. Results The mean value of uNTX of all 227 patients was （84.30±13.29） nmol BCE/mmol Cr, which was significantly higher than the upper limit of normal range （t = 21.875, P〈0.01 ）. Using 65 nmol BCE/mmol Cr as the threshold, 197 cases were diagnosed as with and 30 without bone metastases, in which 188 and 27 were re- spectively confirmed by other examinations. The mean uNTX was （88.73±8.37） and （60.76±9.14） nmolBCE/mmol Cr in patients with and without bone metastases, respectively （t = - 18.134, P〈0.01 ）. The sensi tivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index of uNTX combined with BS were 98.4% （ 188/191）, 75.0% （27/36）, 95.4% （ 188/197）, 90.0% （ 27/30）, 94.7% （215/227） and 73.4% respectively. The cut-off value by ROC curve analysis was 78.88 nmol BCE/mmol Cr and the area under the curve was 0.982. Using 78.88 nmol BCE/mmol Cr as threshold, the corresponding sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 97.4%（186/191）, 94.4%（34/36）, 98.9%（186/188）, 87.2%（34/39）, 96.9%（22/227） and 91.8% re spectively. Condusions Using the cut-off value of 78.88 nmol BCE/mmol Cr, uNTX may have clinical value in helping the differential diagnosis of bone scimigraphy for patients suspected of metastatic bone disease.