PROGRESSION OF OSTEOARTHRITIS

关节软骨生化与代谢的基础研究 已经确定了化合物(例如，金属蛋白酶抑制剂) 在动物模型中显示出巨大的潜力作为疾病的改良剂 治疗骨关节炎的药物(DM0ADs)。骨性关节炎(0A)的研究 社会各界普遍同意联合空间的收窄 (JSN)，在系列X线片中测量，是损失的替代 即关节软骨可以，用标准化的定位 以足够的精度测量受试者以允许检测到 DMOAD效应。然而，对DM0ADs影响的研究一直在进行 不一致和不完整的信息阻碍了 关于最合适目标人群的基本决策(S) 和主要成果变量(即反映 0A的进展)。在此提出的研究将提供 对未来DMOAD设计有用的信息 试验；260名受试者将参加0A的纵向研究 进步。所有科目的年龄均大于或等于45岁 老年人并有特发性双侧或单侧膝0A轻度至... 中等无线电图形严重性(即基本上为Kellgren和 劳伦斯II-III级：明确的骨赘和内侧 胫股(Tf)Jsw大于2 mm)。合格科目 将接受无线电图形检查和ALGO功能检查 评估0A严重性(WOMAC)时为基线，随后为 16到30个月。我们将用并行的方式增加这些数据 最近来自安慰剂组的36名受试者的信息 资助的随机对照试验(RCT)的效果 多西环素治疗0A进展--其方案相同 关于时间和时间方面的本提案的 膝关节X线片技术及功能评定。全 随机对照试验的受试者为女性，年龄45-， 单侧膝关节0A和身体质量指数。 同龄、同种族的女性。Tf、Tf和Tf的骨质变化 髌股(PF)膝0A(如骨赘、软骨下 硬化症)将被半定量评分，而为了精确度 和推广到未来的DMOAD试验，计算机化 最小内侧Tf Jsw的测量将在数字化上进行 两个膝盖的图像，通过标准化定位获得 透视，带图像放大校正功能。

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.