血清基质金属蛋白酶2与骨代谢标志物水平对女童特发性中枢性性早熟的诊断价值研究

Diagnosis Value of the MMP-2 and Bone Metabolism Markers in Girls With Idiopathic Central Precocious Puberty

目的探讨血清基质金属蛋白酶2(MMP-2)与骨代谢标志物水平对女童特发性中枢性性早熟(ICPP)的诊断价值。方法选取2012年10月—2013年8月在温州医科大学附属第二医院就诊的ICPP女性患儿49例(ICPP组)为研究对象,另选择同期在本院诊断为单纯性乳房早发育(PT)的女性患儿40例(PT组)和体检健康女童35例(健康组)为对照。入选儿童均清晨空腹采血,测定血清MMP-2、Ⅰ型前胶原氨基端延长肽(P1NP)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、N端骨钙素(N-MID)、25(OH)D3水平。结果各组MMP-2、P1NP、N-MID水平比较,差异有统计学意义(P<0.05),其中ICPP组MMP-2、P1NP、N-MID水平高于PT组和健康组,PT组MMP-2水平高于健康组(P<0.05)。相关分析显示,MMP-2水平分别与P1NP、β-CTX及N-MID呈正相关(r=0.438、0.260、0.347,P<0.01);P1NP水平与N-MID呈正相关(r=0.657,P<0.01)。MMP-2及骨代谢标志物对ICPP诊断价值的ROC曲线显示,MMP-2曲线下面积最大,取临界值为186μg/L时,约登指数最大,为0.800,灵敏度为0.848,特异度为0.952,阳性预测值为0.966,阴性预测值为0.800,OR=110.65。MMP-2及骨代谢标志物对PT诊断价值的ROC曲线显示,MMP-2曲线下面积最大,取临界值为164μg/L时,约登指数最大,为0.542,灵敏度为0.590,特异度为0.952,阳性预测值为0.958,阴性预测值为0.556,OR=28.75。MMP-2及骨代谢标志物对ICPP与PT鉴别诊断的ROC曲线显示,N-MID曲线下面积最大,取临界值为113μg/L时,约登指数最大,为0.322,灵敏度为0.758,特异度为0.564,阳性预测值为0.585,阴性预测值为0.709,OR=3.45。结论 MMP-2及骨代谢标志物对ICPP的诊断及与PT的鉴别诊断均有一定的临床价值。

Objective To investigate the diagnostic value of serum matrix metalloproteinase（ MMP-2） and bone metabolism markers in diagnosis with idiopathic central precocious puberty（ ICPP） in girls. Methods From October 2012 to August 2013,in the 2nd Affiliated Hospital of Wenzhou Medical University,49 ICPP girls were enrolled in ICPP group,another40 girls with simple premature thelarche（ PT） in PT group,35 healthy girls in control group. The levels of MMP-2,procollagen typeⅠN-terminal propeptide（ P1NP）,β-C-terminaltelopeptide of typeⅠcollagen（ β-CTX）,N-terminal middle molecule osteocalcin（ N-MID） and 25-hydroxyvitamin D were determined. Results There were significant differences in the levels of MMP-2,P1 NP,N-MID among 3 groups（ P〈0. 05）,and higher in ICPP group than in groups PT,control,MMP-2 higher in PT group than in control group（ P〈0. 05）. Correlation analysis showed that MMP-2 was positively correlated with P1 NP,β-CTX and N-MID（ r = 0. 438,0. 260,0. 347,P〈0. 01） and that P1 NP positively with N-MID（ r = 0. 657,P〈0. 01）. By the ROC curve of the diagnostic values of MMP-2 and bone metabolism markers for ICPP,MMP-2 area under the curve was the largest; taking the critical value as 186 μg / L,the Youden index was the biggest（ 0. 800）,sensitivity was 0. 848,specificity was 0. 952,positive predictive value was 0. 966,negative predictive value was0. 800,OR = 110. 65. By the ROC curve of the diagnostic values of MMP-2 and bone metabolism markers for PT,MMP-2area under the curve was the largest; taking the critical value as 164 μg / L, the Youden index was the biggest（ 0. 542）,sensitivity was 0. 590,specificity was 0. 952,positive predictive value was 0. 958,negative predictive value was 0. 556,OR =28. 75. By the ROC curve of the differential diagnosis of MMP-2 and bone metabolism markers for ICPP and PT,N-MID area under the curve was the largest; taking the critical vales as 113 μg / L,the Youden index was the biggest（ 0. 322）,sensitivity was 0. 758, specificity was 0. 564, positive predictive value was 0. 585, negative predictive value was 0. 709, OR = 3. 45.Conclusion MMP-2 and bone metabolism markers are of some clinical values in ICPP diagnosis and the differential diagnosis of ICPP and PT.