来源：风湿病与关节炎,2024,13（7）:16-21.

云克对类风湿关节炎患者骨代谢及Wnt/DKK1相关因子表达研究（临床研究）

唐　芳¹，蒋　总²，秦　瑶²，马武开¹，兰维娅²，刘正奇¹

　　【摘　要】目的：观察云克对类风湿关节炎患者炎症介导骨代谢的治疗效果及安全性，以及对Wnt/DKK1信号通路相关蛋白的影响。方法：选取2020年11月至2021年12月就诊于贵州中医药大学第二附属医院风湿免疫科的60例类风湿关节炎患者为研究对象，按照随机数字表法分为治疗组和对照组，每组30例。对照组给予甲氨蝶呤片联合来氟米特片口服治疗，治疗组在对照组基础上加锝（⁹⁹Tc）亚甲基二膦酸盐注射液（商品名：云克）治疗。治疗前及治疗后第3个月、第6个月、第12个月检测骨密度，以观察骨密度变化百分比；治疗前、治疗后第12周检测Wnt/β-catenin相关因子［β-连环蛋白（β-catenin）、Dickkopf-1相关蛋白（DKK1）、低密度脂蛋白受体相关蛋白（lLRP6）］，细胞因子［白细胞介素（IL）-17、IL-6］，骨代谢标志物［β-CTX、抗酒石酸酸性磷酸酶5b（tTRAP5b）］水平。结果：①治疗组ESR、DAS28-ESR评分、CRP、HAQ、VAS评分，在第4周至第12周均下降，且与对照组相比下降更为明显（P < 0.05）。②治疗12周后，治疗组骨破坏标志物、炎症因子、Wnt信号通路抑制因子DKK1血清水平均较对照组低（P < 0.05），治疗组Wnt通路活化因子β-catenin、LRP6较对照组血清含量高（P < 0.05）。③治疗后，2组脊柱及髋部骨密度变化百分比比较，差异均无统计学意义（P > 0.05）。2组髋部及脊柱骨密度变化百分比均在第12个月与第3个月比较增长明显（P < 0.05）。结论：云克可以改善类风湿关节炎患者临床症状，降低疾病活动度，调节骨代谢，可能通过Wnt/DKK1信号通路介导类风湿关节炎患者骨破坏进展，且安全性较好。

　　【关键词】　类风湿关节炎；云克；Wnt；DKK1；骨代谢；随机对照试验

Effect of Tc-MDP on Bone Metabolism and Wnt/DKK1 Related Factor Expression in RA Patients

TANG Fang,JIANG Zong,QIN Yao,MA Wu-kai,LAN Wei-ya,LIU Zheng-qi

　　【ABSTRACT】 Objective:To observe the therapeutic effect and safety of Tc-MDP on inflammation mediated bone metabolism in RA（rheumatoid arthritis）patients,as well as its impact on Wnt/DKK1 signaling pathway related proteins.Methods:Sixty RA patients who visited the Rheumatology and Immunology Department of the Second Affiliated Hospital of Guizhou University of Chinese Medicine from November 2020 to December 2021 were selected as the study subjects.They were randomly divided into a treatment group and a control group using a random number table method,with 30 patients in each group.The control group orally took methotrexate tablets combined with leflunomide tablets,while the treatment group were treated with Tc-MDP（trade name:Yunke）based on the treatment for the control group.Bone density was measured before treatment and at 3,6,and 12 months after treatment to observe the percentage change in bone density.Wnt/β-catenin related factors（β-catenin,DKK1,lLRP6）,cytokines（IL-17,IL-6）and bone metabolism markers（β-CTX,tTRAP5b）were measured before treatment and at 12 weeks after treatment.Results:The ESR and DAS28-ESR scores,CRP,HAQ,and VAS scores of the treatment group decreased from week 4 to week 12,and the decrease was more significant compared with the control group（P < 0.05）②After 12 weeks of treatment,the serum levels of bone destruction markers,inflammatory factors,and Wnt signaling pathway inhibitor DKK1 in the treatment group were lower than those in the control group（P < 0.05）,while the serum levels of Wnt pathway activator β-catenin and LRP6 in the treatment group were higher than those in the control group（P < 0.05）.③After treatment,there was no statistically significant difference in the percentage change of spinal and hip bone density between the two groups（P > 0.05）.The percentage changes in hip and spinal bone density in both groups increased significantly in the 12th and 3rd months（P < 0.05）.Conclusion:Yunke can improve the clinical symptoms of RA patients,reduce disease activity,regulate bone metabolism,and may mediate the progression of bone destruction in RA patients through the Wnt/DKK1 signaling pathway,with good safety.

　　【Keywords】 rheumatoid arthritis;Yunke;Wnt;DKK1;bone metabolism;randomized controlled trial