Identifying determinants of rapid structural and/or clinical progression in knee osteoarthritis by quantitative assessment of structural features on radiographs

摘要 膝骨性关节炎(KOA)是一个主要的公共卫生问题，影响着大约3000万美国成年人，随着越来越多的人 发病率和过早死亡率。KOA已被确定为最大的未得到满足的医疗需求之一 因为没有FDA批准的治疗方法来预防、减缓或阻止骨性关节炎的进展。 开发和评估潜在的骨性关节炎治疗方法在一定程度上受到了骨性骨性关节炎的阻碍 缓慢进展的疾病，尽管进展是可变的，一些膝盖经历了快速的结构性或临床 进步。 需要可行的高通量方法来获得关于如何识别快速进步者的见解。我们 我开发了一种快速、可重现且反应灵敏的定量软件工具--定量射线照相法 软件得分(QROS)，用于测量最小关节间隙宽度(JSW)，固定JSW(FJSW)，方差为14 FJSW的位置；膝关节对齐/不对齐的程度；以及松质骨的方向和粗糙度 纹理(TBT)。 我们研究的首要目标是确定膝盖有快速进展的高风险，我们的核心概念是 对射线照片上基线结构特征的新组合进行定量评估将 找出一组膝关节结构和/或临床进展迅速的膝关节。我们的中心假设是 膝关节X线片上结构特征的异常将是不同组合的决定因素 膝关节骨性关节炎的结构性和/或临床进展率恶化。我们的方法利用了一种独特的 通过将以下三项结合起来，创新地评估约10,500人的放射学特征的机会 对患有或有发病风险的个体进行最大规模和最具种族多样性的纵向观察研究 KOA：约翰斯顿县骨关节炎项目(JoCoOA)，多中心骨关节炎研究(MOST)，以及 骨性关节炎倡议(OAI)。所有三个队列都有固定的屈曲，负重的膝盖X线片 在多次访问期间使用相同的方案获得，以及关于人口统计、KOA风险的可比数据 因素，以及WOMAC疼痛和功能。 我们的具体目标是：1)。为了定量评估膝关节骨性关节炎的结构和临床进展，分别和 合并；2)。确定膝关节骨性关节炎快速进展的结构决定因素；以及3)。为了确定膝盖- 基于结构和临床决定因素的膝关节置换(KR)的特定概率和时间。

Abstract Knee osteoarthritis (KOA) is a major public health problem that affects ~30 million US adults, with increased morbidity and premature mortality. KOA has been identified as one of the biggest unmet medical needs because there are no FDA-approved treatments available to prevent, slow or halt OA progression. Development and evaluation of potential OA treatments has been hampered in part by KOA typically being a slowly progressive disease, though progression is variable and some knees undergo rapid structural or clinical progression. Feasible high-throughput methods are needed to gain insights as to how to identify rapid progressors. We have developed a rapid, reproducible, and responsive quantitative software tool, Quantitative Radiographic Software Scores (QROS), to measure minimal joint space width (JSW), fixed JSW (fJSW), variance of 14 fJSW locations; degrees of knee alignment/ malalignment; and orientation and roughness of trabecular bone texture (TBT). The overarching goal of our research is to identify knees at high risk of rapid progression, and our core concept is that quantitative assessment of a novel combination of baseline structural features on radiographs will identify a group of knees with rapid structural and/or clinical progression in KOA. Our central hypothesis is that abnormalities of structural features on knee radiographs will be determinants of varying combinations of worsening rates of structural and/or clinical progression in KOA. Our approach takes advantage of a unique opportunity to innovatively assess radiographic features on ~10,500 individuals by combining three of the largest and most racially diverse longitudinal observational studies of individuals with or at risk of developing KOA: the Johnston County Osteoarthritis Project (JoCoOA), the MulticenterOsteoarthritis Study (MOST), and the Osteoarthritis Initiative (OAI). All three cohorts have fixed flexion, weightbearing knee radiographs that were acquired with identical protocols over multiple visits, and comparable data on demographics, KOA risk factors, and WOMAC pain and function. Our specific aims are: 1). To quantitatively assess structural and clinical progression of KOA, separately and combined; 2). To identify the structural determinants of rapid KOA progression; and 3). To determine the knee- specific probability and time to knee replacement (KR) based on structural and clinical determinants.