VU University Medical Center, Department of Rheumatology, De Boelelaan 1117, Amsterdam, The Netherlands.
Ann Rheum Dis. 2010 Sep;69(9):1623-8. doi: 10.1136/ard.2009.121764. Epub 2010 Jun 4.
To determine to what extent baseline measurements of the ratio receptor activator of nuclear factor-kappaB ligand (RANKL):osteoprotegerin (OPG) and C-terminal cross linking of type-I and type-II (CTX-I and CTX-II), in addition to traditional markers of disease severity, could predict annual radiological progression.
A cohort of 155 patients with early, active, untreated rheumatoid arthritis (RA) who participated in the Combination Therapy in Early Rheumatoid Arthritis trial (COBRA trial) was followed up for 11 years. Urine was sampled at baseline and after 3 months from the start of treatment and analysed for CTX-I and CTX-II. Baseline serum samples were analysed for RANKL and OPG. Available traditional markers of disease severity included baseline measurements of erythrocyte sedimentation rate, rheumatoid factor and baseline radiological damage. A digital database of frequent radiographs was available, scored according to the Sharp/van der Heijde method. Individual annual progression rates were calculated and used as outcome variable. Multiple linear regression analyses identified the strongest predictors of annual radiological progression.
In multivariable analyses the RANKL:OPG ratio and CTX-I or CTX-II proved to be independent predictors of annual radiological damage over 11 years. The prediction of annual radiological progression was strongest when the RANKL:OPG ratio and CTX-I or CTX-II were evaluated in the same model (36-39% explained variance). Adding the effect of treatment at 3 months to the baseline models improved the predictive ability of the models up to 44-46%.
Unfavourable baseline levels of the RANKL:OPG ratio as well as CTX-I and CTX-II in patients with early, active, untreated RA are strong independent predictors of rapid and persistent damage progression over the 11-year follow-up. Early improvement in bone markers by treatment predicts a better outcome.
确定基线核因子-κB 配体受体激活剂（RANKL）与护骨素（OPG）比值以及Ⅰ型和Ⅱ型胶原 C 端交联（CTX-I 和 CTX-II）与疾病严重程度的传统标志物相比，在多大程度上可以预测年度放射学进展。
一项纳入 155 例早期、活动期、未经治疗的类风湿关节炎（RA）患者的队列研究，这些患者参与了早期类风湿关节炎联合治疗试验（COBRA 试验），并随访 11 年。在治疗开始后的第 3 个月和基线时采集尿液，分析 CTX-I 和 CTX-II。分析基线血清样本中 RANKL 和 OPG 的含量。可获得的疾病严重程度的传统标志物包括基线红细胞沉降率、类风湿因子和基线放射学损伤的测量值。还可以获得一个根据 Sharp/van der Heijde 评分法对频繁拍摄的 X 线片进行评分的数字数据库。计算个体每年的进展率，并将其作为因变量。采用多元线性回归分析确定年度放射学进展的最强预测因子。
在多变量分析中，RANKL：OPG 比值以及 CTX-I 或 CTX-II 是 11 年内年度放射学损害的独立预测因子。当在同一模型中评估 RANKL：OPG 比值和 CTX-I 或 CTX-II 时，对年度放射学进展的预测最强（解释方差 36-39%）。在基线模型中加入 3 个月时的治疗效果可将模型的预测能力提高至 44-46%。
在早期、活动期、未经治疗的 RA 患者中，基线 RANKL：OPG 比值以及 CTX-I 和 CTX-II 水平较低是快速和持续放射学进展的强烈独立预测因子，可随访 11 年。治疗后骨标志物早期改善预示着更好的预后。
