RADIOGRAPHIC PROGRESSION OF KNEE OSTEOARTHRITIS

关节软骨生化及代谢的基础研究 已确定的化合物(例如，金属蛋白酶抑制剂)具有 在动物模型中显示出作为疾病修改药物的巨大潜力 骨关节炎(DMOADs)。骨关节炎(OA)研究社区 普遍同意关节空间(JSN)变窄， 在系列X线片中测量，是关节丢失的替代指标 认为软骨可以，用标准化的主体定位 以足够的精度测量以允许检测到DMOAD 效果。然而，对DMOADs影响的研究一直受到阻碍 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(S)和主要 结果变量(即反映骨性关节炎进展的指标)。 有人认为，Heberden结点或结果的存在 核素骨显像可能有助于识别患高血压风险增加的受试者 进行性骨性关节炎和最近的流行病学数据表明 选择有单边放射证据的人群 膝关节骨性关节炎与双侧疾病的主要危险因素(女性 性别、肥胖、中年)可能提供了观察(和 预防)在骨关节炎高风险的关节中迅速发病--即， X线片上正常的对侧膝关节。然而，学位 高危对侧膝关节骨性关节炎的骨性改变 这一选定的群体(即骨赘)伴随着JSN IS 未知。 本文建议的研究将提供以下信息： 对设计未来的DMOAD试验很有用；150名受试者将 参加骨性关节炎进展的纵向研究：60名45岁女性-- 30例45岁男性单侧膝骨性关节炎的放射学证据-- 双侧膝关节骨性关节炎，女性30例，男性30例，年龄65-74岁 膝盖骨关节炎。因为肥胖是公认的膝骨性关节炎的危险因素，所有 受试者的身体质量指数(BMI)将为性行为的上三分位数- 、种族和年龄调整的常模。膝盖骨关节炎在以下时间将是轻度/中度 基线[骨赘和大于或等于2毫米的最小值 内侧胫股关节间隙宽度(JSw)]。受试者将接受 膝部和手部的X线检查及功能评定 (WOMAC)在基线上。单侧膝骨性关节炎的患者也将接受 基线骨显像，其结果将与x射线有关 随时间变化以确定核素扫描的预测价值 对于膝骨性关节炎的进展。膝关节X光片将重复15次和15次 基线后30个月。膝关节骨性关节炎的骨质变化(例如，骨赘， 硬化症)将被半定量评分，而为了精确度和 对未来DMOAD试验的概括性，JSN将从 JSw最小内侧腔室的系列计算机测量 在用标准化技术获得的双膝数字化图像中 透视定位，图像校正 放大。

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.