Growth Disturbance in the patients with juvenile rheumatoid arthritis

本研究旨在探讨幼年类风湿性关节炎(JRA)患者慢性炎症对骨代谢和内分泌水平的影响。JRA患者的生长障碍与疾病活动持续进展的JRA患者的生长障碍是一致的。这说明JRA自身的炎症状态导致了生长障碍。JRA患者的生长速度在活动状态时，全身型和多关节型患者的生长速度明显受到抑制，但当疾病活动恢复正常时，生长速度出现追赶现象。缓解期生长速度恢复正常，与健康儿童相当。JRA患者血清IGF-1及其载体蛋白IGFBP3水平在活动期较低，缓解期恢复正常；JRA生长速度与血清骨钙素水平显著相关，与血清透明质酸水平弱相关。双能X线骨矿含量测定结果显示，JRARADUS患者活动期骨矿含量低，非活动期骨矿含量升高，缓解期骨矿含量正常。在本研究中，我们发现JRA患者的炎症程度与生长障碍和骨矿含量下降显著相关，我们提出了以下机制：炎症阶段影响成骨细胞增加的IGF-1/IGFBP3的产生和成熟成骨细胞产生的骨钙素受到抑制。其结果是阻碍了生长板的生长和成骨。

The purpose of this study is to examine how chronic inflammation in the patients with juvenile rheumatoid arthritis (JRA) affects the bone metabolism and endocrine level.1. Growth disturbance in the patients with JRAThe patients with JRA in whom the disease activity continued progressed the growth disturbance in accordance with activity period. This shows inflammation state of JRA itself induces the growth disturbance.2. The growth rate of JRA patientsThe growth rate was remarkably inhibited during the active state in the patients of systemic and polyarticular type, however, there was the catch up phenomenon in the growth rate when the disease activity became normal. In the remission stage, the growth rate returned normal equivalent to the healthy child.3. Growth disturbance and growth related factors in JRAThe level of serum IGF-1 and its carrier protein, IGFBP3, was low in the active state and became normal in the remission stage.The growth rate of JRA showed the significant correlation with serum osteocalcin levels and weak correlation with serum hyaluronic acid levels.4. The bone mineral content in the patients with JRARadius bone mineral content observed by the dual energy X-ray absorptiometry method was low level in the active stage, increased in the non-active stage, and normalized in the remission. There was a significant difference between these three stages.In this study, we showed that the degree of inflammation significantly correlates with growth disturbance and bone mineral content decrease in the patients with JRA.We propose this mechanism as below ; the productions of IGF-1/IGFBP3, which affect the increase of osteoblasts, and osteocalcin produced by mature osteoblasts were inhibited under the inflammation stage. As the result, growth of the epiphyseal plate and osteogenesis were hindered.