PROGRESSION OF OSTEOARTHRITIS

关节软骨生物化学和代谢的基础研究 已经鉴定了化合物（例如，金属蛋白酶抑制剂）， 在动物模型中显示出巨大的潜力， 骨关节炎药物（DM 0AD）。骨关节炎（OA）研究 社区普遍认为，联合空间的缩小 (JSN)在连续X光片中测量的，是损失的替代品。 关节软骨，可以，与标准化的定位， 以足够精确度测量对象以允许检测 DMOAD效果。然而，关于DM 0AD的影响的研究已经被 由于信息不一致和不完整， 关于最适当目标人群的基本决定 和主要结果变量（即，反映措施 0A的发展）。本文提出的研究将提供 这将是有用的信息在未来的DMOAD设计 试验; 260例受试者将入组0A的纵向研究 进展所有受试者的年龄均大于或等于45岁 老年人和有特发性双侧或单侧膝关节0A的轻度至 中等无线电图形严重度（即，基本上是凯尔格伦， Lawrence II-III级：明确的骨赘和内侧 胫股（TF）JSW大于2 mm）。合格受试者 将接受无线电图形检查和算法功能检查 基线和随后的0A严重程度评估（WOMAC） 16和30个月。我们将用并行的 来自安慰剂组的36名受试者的信息， 受资助的随机对照试验（RCT）， 多西环素对0A进展的治疗方案 在时间安排方面， 膝关节X线摄影技术和功能评估。所有 来自RCT的受试者将是45-64岁的女性， 单侧膝关节0A和体重指数在上三分之一， 相同年龄和种族的女性。TF的骨质变化和 髌股（PF）膝关节0A（例如，软骨下骨赘 硬化）将半定量分级，而为了精确， 和推广到未来的DMOAD试验， 最小内侧TF JSW测量将在数字化 双膝的图像，在标准化定位下获得 荧光透视，具有图像放大率校正。

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 (DM0ADs). The osteoarthritis (0A) 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 DM0ADs 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 of 0A). The study proposed herein will provide information which will be useful in the design Of future DMOAD trials; 260 subjects will be enrolled in a longitudinal study of 0A progression. All subjects will be greater then or equal to 45 years old and have idiopathic bilateral or unilateral knee 0A of mild-to- moderate radio graphic severity (i.e., essentially Kellgren and Lawrence Grade II-III: a definite osteophyte and medial tibiofemoral (TF) JSW is greater than 2 mm). Qualified subjects will undergo radio graphic examination and algofunctional assessment of 0A severity (WOMAC) at baseline and subsequently at 16 and 30 months. We will augment these data with parallel information from 36 subjects from the placebo group of a recently funded randomized controlled trial (RCT) of the effects of doxycycline on 0A progression--the protocol for which is identical to that for the present proposal with respect to the timing and technique of knee radiography and algofunctional assessment. All subjects from the RCT will be women, 45-64 years of age, with unilateral knee 0A and body mass index in.the upper tertile for women of the same age and race. Bony changes of TF and patellofemoral (PF) knee 0A (e.g., osteophytes, subchondral sclerosis) will be graded semiquantitatively while, for precision and generalizability to a future DMOAD trial, computerized measurements of minimum medial TF JSW will be made on digitized images of both knees, obtained with standardized positioning under fluoroscopy, with correction for image magnification.