Characterization of Rapidly Progressive Knee Osteoarthritis

 描述(申请人提供)：骨关节炎(OA)，特别是膝骨性关节炎，是导致残疾的15大原因之一，也是关节置换的主要原因，每年花费超过300亿美元。膝骨性关节炎通常是一种进展缓慢的疾病，但对于最近发现的一个亚型来说，疾病的进展速度非常快。这些人出现更频繁和更严重的膝关节疼痛，需要全膝关节置换的可能性是后者的16倍。]由于这是一个新的观察结果，我们还不知道经历[加速膝骨性关节炎(Akoa)]的个体是一种独特的疾病还是膝骨性骨性关节炎的一种加速形式。确定区分或识别阿科阿的因素可以导致预防战略和发现治疗目标。我们的目标是测试Akoa是否具有独特的特征：(I)与损伤和异常负荷相关的解剖特征，(Ii)损害结构(葡萄糖稳态、炎症)的生化因素，(Iii)某些类型的激发病理，以及(Iii)独特的病理过程。]为了实现这些目标，我们建议对骨性关节炎计划中的三组患者进行嵌套病例对照研究。骨关节炎倡议是一项杰出的研究，它对膝骨性关节炎患者或有膝骨性关节炎风险的人进行年度评估；包括磁共振图像、X光和临床测量。我们建议检查的三组将是[1)患阿科阿的膝关节，2)发展为普通骨性关节炎的膝部，]和3)无骨性关节炎的膝部。阿科阿将被定义为在48个月内从基线无放射学膝骨性关节炎进展到终末期骨性关节炎。普通膝关节骨关节炎将被定义为在基线水平没有放射学骨关节炎但在48个月内放射学评分增加的膝关节(不包括定义为阿科阿的膝关节)。最后，没有骨性关节炎的膝关节不会有放射学上的骨性骨性关节炎的进展。我们将评估样本中的年度磁共振图像，以确定和量化膝关节的结构变化。我们还将进行分析，以测量[基线葡萄糖平衡和全身]炎症。最后，我们还将使用OAI提供的血清和尿液生物标记物数据来测量骨骼和软骨的周转。[这些发现可能导致预防战略和发现治疗目标。此外，这项研究产生的见解可能会推广到常规的膝骨性关节炎，扩大整个领域。]

 DESCRIPTION (provided by applicant): Osteoarthritis (OA), particularly knee OA, is among the top 15 causes of disability and the main reason for joint replacement at a cost of over $30 billion/year. Knee OA is typically a slowly progressive disorder but for a recently identified subset the disease progresses with dramatic rapidity. These individuals develop more frequent and severe knee pain, and are 16 times more likely to require a total knee replacement.] Since this is a novel observation, we do not yet know whether individuals experiencing [accelerated knee OA (AKOA) is a distinct disease or an accelerated form of knee OA. Determining factors that differentiate or identify AKOA could lead to preventive strategies and uncover therapeutic targets. Our goals are to test if AKOA can be uniquely characterized by: (i) anatomical characteristics associated with injuries and abnormal loading, (ii) biochemical factors that compromise structures (glucose homeostasis, inflammation), (iii) certain types of instigating pathology, and (iiii) distinct pathological processes.] To achieve these goals we propose to perform a nested case-control study with three groups selected from the Osteoarthritis Initiative. The Osteoarthritis Initiative is an outstanding study that conducts annual evaluations; including magnetic resonance images, x- rays, and clinical measurements; of people with or at risk for knee OA. The three groups we propose to examine will be [1) knees that develop AKOA, 2) knees that develop common OA,] and 3) knees with no OA. AKOA will be defined as knees that progress from no radiographic OA at baseline to end-stage OA within 48- months. Common knee OA will be defined as knees with no radiographic OA at baseline but increase in radiographic scoring within 48 months (excluding those defined as AKOA). Finally, no OA will be knees with no radiographic OA and do not progress. We will assess annual MR images in the sample to identify and quantify structural changes in the knee. We will also perform assays to measure [baseline glucose balance and systemic] inflammation. Finally, we will also use serum and urine biomarker data provided by the OAI to measure bone and cartilage turnover. [These findings could lead to preventive strategies and uncover therapeutic targets. Furthermore, the insights generated from this study may generalize to regular knee OA, expanding the overall field.]