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

摘要 膝关节骨关节炎（KOA）是一个主要的公共卫生问题，影响到约3000万美国成年人， 发病率和过早死亡率。KOA已被确定为最大的未满足的医疗需求之一 因为没有FDA批准的治疗方法可用于预防，减缓或停止OA进展。 潜在OA治疗方法的开发和评估受到阻碍，部分原因是KOA通常是 缓慢进展的疾病，尽管进展是可变的，一些膝关节经历快速的结构或临床 进展 需要可行的高通量方法来深入了解如何识别快速进展者。我们 我开发了一种快速、可重复、响应迅速的定量软件工具，定量放射学 软件评分（QROS），用于测量最小关节间隙宽度（JSW），固定JSW（fJSW），方差为14 fJSW位置;膝关节对线/对线不良的程度;以及骨小梁的方向和粗糙度 纹理（TBT）。 我们研究的首要目标是识别快速进展高风险的膝关节，以及我们的核心概念 对射线照片上基线结构特征的新组合的定量评估将 确定一组KOA结构和/或临床进展迅速的膝关节。我们的核心假设是， 膝关节X线片上的结构特征异常将是不同组合的决定因素， KOA的结构和/或临床进展恶化率。我们的方法利用了独特的 有机会通过结合以下三种方法，创新性地评估约10，500人的放射学特征： 对患有或有风险发展为糖尿病的个体进行的最大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 Osteoarthritis Initiative（OAI）。所有三个队列均具有固定屈曲、负重膝关节X线片， 在多次访视中使用相同的方案获得，并获得人口统计学、KOA风险 WOMAC疼痛和功能。 我们的具体目标是：1）。分别定量评估KOA的结构和临床进展， 合并; 2）.确定KOA快速进展的结构决定因素; 3）。为了确定膝盖- 基于结构和临床决定因素的膝关节置换术（KR）的具体概率和时间。

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.