RADIOGRAPHIC PROGRESSION OF KNEE OSTEOARTHRITIS

关节软骨生化和代谢的基础研究， 识别的化合物（例如，金属蛋白酶抑制剂）， 在动物模型中显示出作为疾病修饰药物的巨大潜力， 骨关节炎（DMOAD）。 骨关节炎（OA）研究社区 普遍认为关节间隙变窄（JSN）， 在连续X线片中测量，是关节丢失的替代品 软骨，可以通过受试者的标准化定位， 以足够的精度测量，以允许检测DMOAD 效果 然而，对DMOAD影响的研究受到阻碍 不一致和不完整的信息作为决策的基础 关于最合适的目标人群和主要 结果变量（即，反映OA进展的指标）。 有人认为，Heberden节点或结果的存在 骨密度成像可能有助于识别风险增加的受试者， 进行性OA和最近流行病学数据表明， 选择有单侧放射学证据的人群 膝关节OA和双侧疾病的主要危险因素（女性 性，肥胖，中年）可以提供一个观察的机会（和 预防）OA在高风险关节中的快速发作-即， 对侧膝关节放射学检查正常。 然而，程度 高风险对侧膝关节OA的骨变化 该选择组（即骨赘病）伴有JSN， 未知 本报告建议的研究将提供资料， 在未来DMOAD试验的设计中有用;将有150名受试者 入组OA进展的纵向研究：60名年龄45-64岁的女性 有单侧膝关节OA的影像学证据，30名男性，年龄45-64岁 双侧膝关节OA，30名女性和30名男性，年龄65-74岁，双侧 膝关节OA。 由于肥胖是膝关节OA的公认危险因素，所有 受试者的体重指数（BMI）在性别的上三分位数- 种族和年龄调整的标准。 膝关节OA为轻度/中度， 基线[骨赘和大于或等于2 mm的最小值 内侧胫股关节间隙宽度（JSW）]。 受试者将接受 膝、手X线检查及功能评定 （WOMAC）。 单侧膝关节OA患者也将接受 基线骨造影，其结果将与X线检查相关 随时间的变化，以确定动脉造影的预测价值 膝关节OA的进展。 将重复15次膝关节X线摄影， 基线后30个月。膝关节OA的骨性变化（例如，骨赘， 硬化症）将进行半定量分级，而为了精确度和 对于未来的DMOAD试验，JSN将从 JSW最小内侧间室的计算机连续测量 在双膝数字化图像中， 透视下定位，图像校正 倍率

Basic research on articular cartilage biochemistry and metabolism has identified compounds (e.g., metalloproteinase inhibitors) that have shown great potential in animal models as disease-modifying drugs for osteoarthritis (DMOADs). The osteoarthritis (OA) research community is in general agreement that narrowing of the joint space (JSN), measured in serial radiographs, is a surrogate for loss of articular cartilage that can, with standardized positioning of the subject be measured with sufficient accuracy to permit detection of a DMOAD effect. However, research on the effects of DMOADs has been hampered by inconsistent and incomplete information on which to base decisions regarding the most appropriate target population(s) and primary outcome variables (i.e., measures reflecting progression f OA). It has been suggested that the presence of Heberden's nodes or results of bone scintigraphy may help identify subjects at increased risk for progressive OA and that recent epidemiologic data suggest that a select population of persons with radiographic evidence of unilateral knee OA and the cardinal risk factors for bilateral disease (female sex, obesity, middle age) may afford an opportunity to observe (and prevent) the rapid onset of OA in a joint at high risk for OA - i.e., the radiographically normal contralateral knee. However, the degree to which bony changes of OA in the high-risk contralateral knee of this select group (i.e. osteophytosis) are accompanied by JSN is unknown. The study proposed herein will provide information which will be useful in the design of future DMOAD trials; 150 subjects will be enrolled in a longitudinal study of OA progression: 60 women age 45-64 with radiographic evidence of unilateral knee OA, 30 men age 45-64 with bilateral knee OA, 30 women and 30 men age 65-74 with bilateral knee OA. Because obesity is a recognized risk factor for knee OA, all subjects will have body mass index (BMI) in the upper tertile for sex- , race-, and age-adjusted norms. Knee OA will be mild/moderate at baseline [osteophytes and greater than or equal to 2 mm of minimum medial tibiofemoral joint space width (JSW)]. Subjects will undergo x-ray examination of knees and hands and algofunctional assessment (WOMAC) at baseline. Those with unilateral knee OA will also undergo baseline bone scintigraphy, results of which will be related to x-ray changes over time to ascertain the predictive value of scintigraphy for progression of knee OA. Knee radiography will be repeated 15 and 30 months after baseline. Bony changes of knee OA (e.g., osteophytes, sclerosis) will be graded semiquantitatively while, for precision and generalizability to a future DMOAD trial, JSN will be quantitated from serial computerized measurements of minimum medial compartment of JSW in digitized images of both knees obtained with standardized positioning under fluoroscopy, with correction for image magnification.