Graves病诊治与骨转换标志物的相关性研究

Correlation between Graves′disease and bone turnover markers

目的探讨Graves病(GD)患者相关指标与骨转换标志物(BTMs)的关系及其治疗前后变化的预测价值。方法回顾性研究458例GD患者和109名健康体检者(对照组)。比较2组的甲状腺激素[游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)]和BTMs[骨钙素、Ⅰ型前胶原N-末端肽(PⅠNP)、Ⅰ型胶原C-末端肽(CTX)]水平。采用单、多因素分析探讨GD患者14项相关指标与BTMs的相关性。所有GD患者均接受抗甲状腺药物(ATD治疗组)或放射性碘治疗(RAI治疗组)。绘制受试者工作特征(ROC)曲线,分析治疗后FT3、FT4水平/治疗前FT3、FT4水平(FT3-P/FT3-A,FT4-P/FT4-A)的变化对BTMs是否恢复正常的预测价值。结果GD组FT3、FT4、骨钙素、PⅠNP、CTX水平均显著高于对照组(P<0.05),治疗6个月后均有所下降。FT3、FT4、促甲状腺素受体抗体(TRAb)、血钙和碱性磷酸酶(ALP)是预测骨钙素升高的危险因素。病程、FT3、25-羟维生素D(25-OHD)、ALP是预测PⅠNP升高的危险因素。年龄、病程、FT3、血钙和ALP是预测CTX升高的危险因素。ATD治疗组FT3-P/FT3-A和FT4-P/FT4-A预测骨钙素恢复的曲线下面积(AUC)分别为0.680和0.640(P<0.05),临界值分别为0.535和0.595。RAI治疗组FT3-P/FT3-A和FT4-P/FT4-A预测骨钙素恢复的AUC分别为0.730和0.670(P<0.05),临界值分别为0.355和0.595,2个治疗组对PⅠNP和CTX的恢复无预测价值(P>0.05)。结论GD患者的BTMs异常升高。ATD治疗6个月后FT3下降超过46.5%,FT4下降超过40.5%;RAI治疗组治疗6个月后FT3下降超过64.5%,FT4下降超过40.5%是GD骨形成指标骨钙素恢复的独立预测因子。

Objective To explore the relationship between relevant indicators and bone turnover markers(BTMs)in patients with Graves′disease(GD),and the predictive value of their changes before and after treatment.Methods The data of 458 patients with GD and 109 healthy subjects(control group)were analyzed retrospectively.The levels of thyroid hormones[free triiodothyronine(FT3),free thyroxine(FT4),thyrotropin(TSH)]and BTMs[osteocalcin(OST),N-terminal peptide of typeⅠprocollagen(PⅠNP),C-terminal peptide of typeⅠcollagen(CTX)]were compared between the two groups.The correlation between 14 clinical indexes and BTMs was tested with unifactorial and multifactorial analysis.All GD patients received antithyroid drugs(ATD treatment group)or radioactive iodine(RAI treatment group).Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of post-treatment FT3 level/pre-treatment FT3 level(FT3-P/FT3-A)and post-treatment FT4 level/pre-treatment FT4 level(FT4-P/FT4-A)on restoration of BTMs to normal.Results The levels of FT3,FT4,OST,PⅠNP and CTX in GD group were significantly higher than those in control group(P<0.05),and decreased after 6 months of treatment.FT3,FT4,thyrotropin receptor antibody(TRAb),Ca,and alkaline phosphatase(ALP)were risk factors for predicting OST elevation.Disease duration,FT3,25-hydroxyvitamin D(25-OHD)and ALP were risk factors for PⅠNP elevation.Age,course of disease,FT3,Ca,and ALP were risk factors for the elevation of CTX.The area under curve(AUC)of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery in ATD treatment groups were 0.680 and 0.640(P<0.05),and the cutoff values were 0.535 and 0.595,respectively.Whereas,the AUC of RAI treatment groups were 0.730 and 0.670(P<0.05),and the cutoff values were 0.355 and 0.595,respectively.There was no predictive value for PⅠNP and CTX recovery in the two treatment groups(P>0.05).Conclusion BTMs was abnormally elevated in GD patients.A decrease in FT3 greater than 46.5%and FT4 greater than 40.5%after 6 months of ATD treatment,as well as 64.5%and 40.5%drop after RAI treatment were independent predictors of OST recovery in GD patients.