硫酸氨基葡萄糖和双醋瑞因治疗成人大骨节病疗效比较的研究

A comparative study of the efficacy of glucosamine sulfate and diacerein in the treatment of adult Kashin-Beck disease

目的观察比较硫酸氨基葡萄糖(GS)和双醋瑞因(DCN)对成人大骨节病(KBD)的治疗效果。方法采用临床随机对照试验,在黑龙江省KBD历史重病区繁荣乡、富路镇、龙安桥镇、亮河镇、绍文乡,根据《大骨节病诊断》(WS/T 207-2010)标准选取患者240名,采用随机数字表法分为GS、DCN组(性别、年龄、KBD病情分度均衡),分别为120、120名。每个月进行1次随访,调查患者用药情况和临床症状,并发放下一阶段药物。在治疗前、中、末期(0、90、180 d)采集患者的空腹血样和尿样,采用酶联免疫吸附试验(ELISA)检测患者血清白细胞介素(IL)-1β含量以及尿吡啶酚(PYD)水平。通过调查问卷进行视觉模拟量表(VAS)评分、受累关节评估、疗效自我评价、不良反应评估,依据《大骨节病治疗效果判定》(WS/T 79-2011)标准进行关节功能障碍评分和药物疗效判定。结果软骨代谢相关细胞因子表达:治疗180 d,GS组血清IL-1β含量、尿PYD水平和DCN组尿PYD水平均低于同组治疗0 d时(Z=-2.332、-5.420、-5.204,P均<0.05)。VAS评分:治疗90 d,GS组患者疼痛、僵硬评分和DCN组疼痛、僵硬、功能评分均低于同组治疗0 d时(Z=-2.612、-2.359,-3.637、-2.881、-2.238,P均<0.05);治疗180 d,GS、DCN组患者疼痛、僵硬和功能评分均明显低于同组治疗0 d时(Z=-6.738、-9.530、-7.781,-5.428、-3.761、-3.587,P均<0.01)。受累关节评估:治疗90、180 d,除DCN组天气变化疼痛外,两组其余症状关节评分均低于治疗同组0 d时(P均<0.05)。疗效自我评价:治疗180 d,DCN组患者疗效自我评价显效率高于GS组和同组治疗90 d时(χ^(2)=4.165、4.022,P均<0.05)。不良反应评估:治疗90、180 d时,GS、DCN组患者不良反应主要为胃肠道症状。关节功能障碍评分:治疗90 d,GS组患者治疗有效率与显效率之和高于DCN组(χ^(2)=4.993,P<0.05);而治疗180 d时两组间比较差异无统计学意义(χ^(2)=0.417,P>0.05)。结论GS和DCN对成人KBD均有一定的治疗作用,可改善临床症状。GS起效快,且长期服用可在一定程度上保护软骨免受炎症因子侵害。

Objective To observe and compare the therapeutic effects of glucosamine sulfate(GS)and diacerein(DCN)on adult Kashin-Beck disease(KBD).Methods A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township,Fulu Town,Long'anqiao Town,Lianghe Town,Shaowen Township of Heilongjiang Province,and 240 patients were selected according to the criteria of"Diagnosis of Kashin-Beck Disease"(WS/T 207-2010),then divided into GS and DCN groups(gender,age,and KBD condition balanced)via the random number table method,with 120 patients in each group.Followed up once a month to investigate the patient's medication and clinical symptoms,and distributed drugs for the next stage.Fasting blood samples and urine samples were collected before,during,and at the end of treatment(0,90,and 180 days).Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum interleukin(IL)-1β level and urine pyridinol(PYD)level.Visual analog scale(VAS)scores,evaluation of affected joints,self-evaluated efficacy,and evaluation of adverse reactions were carried out through questionnaires.Joint dysfunction scores and medications efficacy determination were performed according to the"Judgment of Kaschin-Beck Disease Treatment Effect"(WS/T 79-2011).Results Expression of cytokines related to cartilage metabolism:after 180 days of treatment,serum IL-1β levels,urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment(Z=-2.332,-5.420,-5.204,P<0.05).VAS scores:after 90 days of treatment,the pain,stiffness scores of patients in GS group and the pain,stiffness,and function scores in DCN group were lower than those in the same group at 0 day of treatment(Z=-2.612,-2.359,-3.637,-2.881,-2.238,P<0.05);after 180 days of treatment,the pain,stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment(Z=-6.738,-9.530,-7.781,-5.428,-3.761,-3.587,P<0.01).Evaluation of affected joints:after 90 and 180 days of treatment,except for pain of weather changes in DCN group,the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment(P<0.05).Efficacy self-evaluation:after 180 days of treatment,the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment(χ^(2)=4.165,4.022,P<0.05).Evaluation of adverse reactions:after 90 and 180 days of treatment,the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms.Joint dysfunction scores:after 90 days of treatment,the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group(χ^(2)=4.993,P<0.05);while after the 180 days of treatment,there was no significant difference between the two groups(χ^(2)=0.417,P>0.05).Conclusions Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms.The GS takes effect quickly,and long-term use can protect cartilage from inflammatory factors to a certain extent.