强直性脊柱炎患者血清硬骨素水平与放射学变化的关系

Correlation between sclerostin level and radiographic changes in patients with ankylosing spondylitis

目的 探讨强直性脊柱炎（AS）患者血清硬骨素水平与放射学变化的关系.方法 选择2012年5月至2013年12月南京医科大学第二附属医院风湿免疫科收治的65例AS患者（AS组）,患者接受注射用重组人Ⅱ型肿瘤坏死因子受体—抗体融合蛋白（益赛普）治疗,随访1年.同期45例健康体检者作为对照组.分别在基线状态、治疗后12个月时评估AS患者各项临床指标（年龄、性别、病程、疾病活动度）、影像学进展以及炎症的指标[红细胞沉降率（ESR）、C反应蛋白（CRP）]、疾病功能指数依据BASFI评分标准,疾病活动指数依据BASDAI评分标准,活动度衡量指数依据BASMI评分标准,放射学指数依据BASRI评分标准,放射学进展以mSASSS评分标准为依据,采用酶联免疫法检测AS患者血清硬骨素浓度.运用相关分析法分析硬骨素与疾病活动度、影像进展及炎症生物标志的关系.结果 AS组在基线状态时ESR及血清CRP水平高于对照组,但硬骨素浓度（55.6±19.5） pmol/L低于对照组（78±27.6）pmol/L,P＜0.01;AS组在治疗12个月时,ESR及血清CRP水平较基线状态时明显下降（P＜0.01）,治疗后12个月时,BASFI、BASMI和BASDI评分较基线状态时明显改善（P＜0.01）,但在治疗后12个月时,硬骨素浓度（62±15.3） pmol/L较基线状态时稍有升高（P=0.25）,仍低于对照组（78±27.6）pmoL/L,P＜0.01.ROC曲线分析显示,硬骨素水平62.75 pmol/L为截断点,该点诊断的敏感度为82.02％,特异度为91.50％,曲线下面积（AUC）为0.905;诊断效力高.相关分析显示,AS组患者在基线状态时和治疗后12个月时,血清硬骨素水平与ESR、CRP、BASFI、BASMI以及BASDAI评分无明显相关性.而放射学指数BASRI及影像学mSASSS评分在基线状态和治疗后差异无统计学意义,且mSASSS评分与硬骨素水平在基线状态和治疗12个月时呈显著负相关（r=-0.768,P＜0.01）.结论 TNF拮抗剂对AS患者血清硬骨素水平无明显影响,且血清硬骨素水平与放射学评分具有明显相关性,提示血清硬骨素的产生可能与炎症状态无明显相关性,TNF拮抗剂可能对AS骨化进程无明显阻止作用.AS患者血清硬骨素可作为一种新的血清诊断骨化指标及反映影像学进展的生物标志.

Objective To explore the serum level of sclerostin in ankylosing spondylitis （AS） patients and evaluate its diagnostic value and the relationship of sclerostin with inflammation and ossification process in AS.Methods A total of 75 AS patients and 45 healthy controls were enrolled into this randomized controlled study.The clinical indices （age,gender,course of disease and disease activity）,changes in radiographic studies and indices of bone metabolism or inflammation,including erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP） were evaluated or measured.The disease activity was assessed by Bath ankylosing spondylitis disease activity index （BASDAI）,Bath ankylosing spondylitis functional index （BASFI）,Bath ankylosing spondylitis metrology index （BASMI） and Bath arthritis spondylitis radiology index （BASRI）.And radiographic changes were evaluated according to the modified Stoke AS spine score （mSASSS） and serum level of sclerostin was measured by enzyme-linked immunosorbent assay （ELISA）.The relationship between sclerostin and clinical indices,radiographic scores and inflammatory indices was estimated by SPSS software and the diagnostic value of sclerostin analyzed by receiver operator characteristic （ROC） curve.Results The levels of ESR and CRP were higher in AS patients than those in healthy controls.However,serum sclerostin was lower （55.6± 19.5 pmol/L） compared with healthy controls （78 ±27.6 pmol/L,P 〈0.01）.ROC analysis revealed that the diagnostic specificity and sensitivity of sclerostin were 91.5% and 82.02% respectively with a cut-off of 62.75 pmol/L （Youden index 0.735,AUC 0.905,95% Cl 0.812-0.947）.And the diagnostic validity was high.No significant correlation existed between sclerostin and ESR,CRP,BASDAI,BASMI and BASFI scores.ESR,CRP,BASDAI,BASMI and BASFI score were improved significantly in AS patients after anti-TNF treatment compared with baseline （P 〈 0.01）.There was little difference between BASRI and mSASSS score after anti-TNF treatment compared with baseline （P =0.19,0.67）.A significant negative correlation existed between the radiographic progression in spine of patients with AS and sclerostin serum levels （r =0.768,P 〈 0.01）.This correlation became stronger when radiographic scores rose （mSASSS 〉 10,r =0.768,P 〈 0.01） and it diminished when radiographic scores dropped （0 〈 mSASSS 〈 10,r =-0.097,P =0.43）.Conclusion Serum sclerostin may serve as a diagnostic biomarker of AS and progression index of ossification,especially in late stage of AS.A low serum level of sclerostin in the setting of AS is linked to greater structural damage.