25-羟基维生素D水平对类风湿关节炎相关指标的影响

Effects of 25-hydroxyvitamin D levels on disease-related factors of rheumatoid arthritis

目的探讨维生素D补充剂对类风湿关节炎(RA)相关指标的影响。方法2014年10月至2018年10月,在中国医科大学附属盛京医院风湿免疫科招募首诊RA患者和健康对照者,统计RA组患者病程、晨僵时间、压痛关节数、肿胀关节数、C反应蛋白(CRP)、血沉(ESR)、类风湿因子(RF)、抗环瓜氨酸肽(ACCP)抗体以及双手X片情况,记录患者整体健康(GH)参数,计算28处关节疾病活动性(DAS28)评分。酶联免疫吸附试验(ELISA)法检测入组时两组受试者血清25-羟基维生素D[25(OH)D]水平,选取25(OH)D缺乏或不足的RA患者及健康对照者给予一次性口服补充维生素D3制剂30万U,间隔4周复测2组补充后的血清25(OH)D水平。分析两组25(OH)D水平在维生素D3干预前、后及前后差值的差异,Spearman相关分析评价初始两组受试者25(OH)D水平和维生素D3干预前后25(OH)D差值水平与DAS28、CRP、RF、ACCP、GH、压痛关节数、肿胀关节数的相关性。结果入组RA组268例首诊RA患者,对照组295例健康检查者,两组一般资料(年龄及性别)比较差异无统计学意义(P>0.05)。1月、2月、6月、7月、8月、9月,RA组25(OH)D水平低于对照组(P<0.05),其余6个月两组比较差异无统计学意义(P>0.05)。维生素D3干预后,两组血清25(OH)D水平在全年差异均有统计学意义(P<0.05)。两组干预前后25(OH)D差值比较差异有统计学意义(P<0.05)。Spearman相关性分析显示,初始25(OH)D水平与DAS28、CRP、GH、压痛关节数、肿胀关节数均为弱相关(相关系数为-0.386、-0.371、-0.323、-0.324、-0.290),与RF、ACCP水平无相关;干预前后25(OH)D水平差值与DAS28、CRP、GH、肿胀关节数、压痛关节数呈明显相关(相关系数-0.802、-0.719、-0.695、-0.559、-0.655),与RF、ACCP水平无相关。结论首诊RA患者25(OH)D水平偏低主要由于消耗增多引起,维生素D干预后,25(OH)D提升水平与RA疾病活动指标DAS28、CRP、GH、肿胀关节数呈明显负相关。

Objective To investigate the effects of vitamin D supplementation on disease-related factors of rheumatoid arthritis(RA).Methods Newly diagnosed RA patients and healthy controls were recruited in Rheumatology and Immunology Department of Shengjing Hospital of China Medical University from October 2014 to October 2018.The course of disease,morning stiffness,the number of tender joints and swelling joints,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),rheumatoid factor(RF),anti-cyclic citrullinated peptide(ACCP)antibody,X-rays of both hands and global health(GH)parameters of patients were recorded;the 28 joints Disease Activity Score(DAS28)in RA group was calculated.Enzyme-linked immunosorbent assay(ELISA)method was used to detect the serum 25-hydroxyvitamin D levels at the time of enrollment.A one-time vitamin D3 supplement(VD3 oral solution 300000 U)was given to patients and healthy controls with vitamin D deficiency,and the serum 25-hydroxyvitamin D levels of the two groups were re-measured at intervals of 4 weeks.Analyze the difference of 25-hydroxyvitamin D level between the two groups before and after vitamin D3 intervention.Spearman correlation analysis was used to evaluate the correlation of 25-hydroxyvitamin D level and changes of 25-hydroxyvitamin D level before and after VD3 intervention with DAS28,CRP,RF,ACCP,GH,and the number of tender joints and swelling joints.Results A total of 268 newly diagnosed RA patients in RA group and 295 healthy subjects in control group were included.There was no significant difference in age or gender between the two groups(P>0.05).In January,February,June,July,August,and September,the 25(OH)D level in RA group was lower than that in control group(P<0.05),while there was no statistical difference in the other months.After vitamin D3 intervention,there were significant differences in the levels of 25(OH)D between the two groups throughout the year.The difference in 25(OH)D before and after intervention was significant between the two groups(P<0.05).Spearman correlation analysis indicated that the initial level of 25(OH)D was weakly correlated with DAS28,CRP,GH,and the number of tender joints,or swelling joints(Spearman correlation factors were -0.386,-0.371,-0.323,-0.324,and -0.290,respectively),but it was not correlated with RF or ACCP levels.The difference in 25(OH)D before and after intervention was correlated with DAS28,CRP,GH,and the number of tender joints and swelling joints(correlation factors were -0.802,-0.719,-0.695,-0.559,and-0.655,res-pectively),but was not correlated with RF or ACCP levels.Conclusion Low 25(OH)D levels in newly diagnosed RA patients are mainly caused by increased consumption.The improvement in 25(OH)D level after intervention of vitamin D is negatively correlated with RA disease activity indicators,such as DAS28,CRP,GH,and the number of swollen joints.