【摘要】 目的研究重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)联合甲氨蝶呤(EM组)、青霉胺联合甲氨蝶呤(PM组)、青霉胺、甲氨蝶呤联合阿仑膦酸钠(PMA组)治疗方案对类风湿关节炎(RA)患者放射学、骨密度(BMD)变化的疗效,并评估血清骨代谢标志物对RA患者骨丢失评价的作用。方法采用病例配对、开放性研究,90例活动性RA患者配对进入3个治疗组。在治疗第0,12,24周收集临床指标并检测骨代谢标志物,在治疗第0,24周进行双手、腕X线摄片及BMD检测。主要采用单因素方差分析法和Pearson相关分析进行统计学处理。结果治疗24周后,EM组Sharp评分进展显著小于PM和PMA组(P<0.01);PMA组腰椎BMD值增加(P<0.05);EM组Ⅰ型胶原吡啶交联末端肽(ⅠCTP)下降值大于PM和PMA组(P<0.05),EM组和PMA组的抗酒石酸酸性磷酸酶5b(TRACP-5b)的下降值大于PM组(P<0.05),PMA组的I型胶原羧基末端肽(C区)β降解产物(β-CTX)下降值大于EM和PM组(P<0.01),EM组骨钙素(BGP)上升,较PM、PMA组BGP下降差异有统计学意义(P<0.05,P<0.01)。基线ⅠCTP值与健康评估问卷(HAQ)、疾病活动指数(DAS)28、Sharp评分呈正相关,TRACP-5b、β-CTX值与腰椎BMD值呈负相关。治疗后ⅠCTP、TRACP-5b的变化值与Sharp评分变化值呈正相关,BGP变化值与Sharp评分变化值呈负相关,β-CTX变化值与BMD变化值呈负相关。结论 rhTNFR:Fc联合甲氨蝶呤治疗可延缓RA患者关节放射学进展。阿仑膦酸钠可增加腰椎BMD,但不能阻止关节放射学进展。血清骨代谢标志物与Sharp评分、BMD相关,可反映RA患者局部或全身骨丢失状况。更多还原

【Abstract】 Objective To determine the effects of various regimens-namely, recombinant human tumor necrosis factor-receptor Ⅱ-IgG Fc fusion protein (rhTNFR:Fc) plus methotrexate (group EM), penicillamine plus methotrexate (group PM) and penicillamine plus methotrexate and alendronate (group PMA)-on radiological scaling and bone mineral density (BMD) in patients with rheumatoid arthritis (RA), and to assess the roles that serum markers of bone metabolism play on loss of bone. Methods In this case-matched, open-labeled study, 90 patients with active RA were allocated to three treatment groups, in a matched fashion. Serum markers of bone metabolism were assayed at post-treatment weeks 0, 12 and 24. Assessment of BMD and X-ray roentgenography on both hands and wrists were performed at weeks 0 and 24. Univariate analysis of variance (ANONA) and Pearson′s correlation model were employed for statistical analysis. Results At week 24, Group EM was featured by a lower Sharp progression scaling than groups PM and PMA (both P<0.01). Group PMA yielded an increased BMD of lumbar spine (P<0.05). A more significant decrease in pyridinoline cross-linked carboxy-terminal telopeptide of type Ⅰ collagen (ICTP) was found in group EM, but not in groups PM and PMA (both P<0.05). While groups EM and PMA resulted in a greater decline in serum tartrate-resistant acid phosphatase 5b (TRACP-5b) than PM group (both P<0.05), the latter group was associated with a markedly reduced level of β-carboxy-terminal cross-linking telopeptide of type Ⅰ Collagen (β-CTX) as compared with groups EM and PM (both P<0.01). Group EM showed a considerably increased bone gamma-carboxyglutamic-acid-containing proteins (BGP), whilst groups PM and PMA were associated with reduced levels of BGP (P<0.05 and 0.01, respectively). Baseline ICTP was positively correlated with HAQ, DAS28 and Sharp score, whilst TRACP-5b and β-CTX were negatively correlated with BMD of lumbar spine. Post-treatment ICTP and TRACP-5b, however, were positively correlated with Sharp score. Changes in post-treatment BGP were negatively correlated with Sharp score, and changes in β-CTX were negatively correlated with that in BMD. Conclusion Radiologic progression of joints in patients with RA may be tempered by the combination of rhTNFR:Fc and methotrexate. Alendronate increases bone mineral density of lumbar spine yet fails to prevent radiological progression of joints. Serum markers of bone metabolism were correlated with Sharp score and BMD and may reflect local or systemic bone loss in patients with RA.更多还原