Trial of Vitamin D to Reduce Progression of Knee OA

描述（由申请人提供）：症状性膝关节骨关节炎的发病率为240/100，000人年，是下肢任务依赖性的最常见原因之一，尤其是在老年人中。它每年造成6800万个工作日的损失，占年退休率的5%以上。骨关节炎是关节置换的最常见原因，每年给社区带来数十亿美元的成本。目前还没有有效的治疗骨关节炎的药物。然而，制药行业正在尝试开发延缓OA进展的药物。如果有效的话，这些专利药物在OA流行的人群中使用将是昂贵的。具有讽刺意味的是，有证据表明，维生素D补充剂，一种简单的非专有干预措施，可能在减缓OA进展方面有效。即使只有适度的效果，它可以在减少OA的社会负担方面产生相当大的影响。因此，为了公众健康的利益，维生素D补充剂作为OA疾病改善治疗的有效性需要在严格的临床试验中进行测试。 由于影像学技术的局限性，膝关节OA的疾病改良试验一直很困难。然而，MRI已经成为一种有效的，精确的和可重复的工具，用于获得软骨和关节结构的体积测量。 我们的目标是招募140名有症状的膝关节OA患者参加为期2年的随机安慰剂对照维生素D临床试验，14，000 ID /周。结局将包括WOMAC问卷（主要临床）、软骨体积损失（主要病理学）、身体功能检查、SF-36和全器官膝关节MRI OA严重程度评分。骨密度、钙稳态和膝关节对线将作为中间变量进行检验。我们将使用横截面时间序列回归模型测试维生素D的有效性，其中一阶自回归扰动调整了信息性辍学。

DESCRIPTION (provided by applicant): Symptomatic knee osteoarthritis has an incidence of 240/100,000 person years and is one of the most frequent causes of dependency in lower limb tasks, especially in the elderly. It causes 68 million work loss days per year and more than 5% of the annual retirement rate. Osteoarthritis is the most frequent reason for joint replacement at a cost to the community of billions of dollars per year. No effective medical remedies for osteoarthritis currently exist. However, the pharmaceutical industry is attempting to develop drugs that retard progression of OA. If efficacious, these proprietary medications will be expensive to employ in a population in which OA is endemic. Ironically, there is evidence that vitamin D supplementation, a simple non-proprietary intervention, may have efficacy in slowing progression of OA. Even if only modestly effective, it could have considerable impact in terms of reducing the societal burden of OA. Therefore, in the interests of public health, the efficacy of vitamin D supplementation as a disease-modifying treatment for OA needs to be tested in a rigorous clinical trial. Disease-modification trials for knee OA have been difficult due to limitations of the radiographic technique. However, MRI has emerged as a valid, precise and reproducible tool for obtaining volumetric measures of cartilage and joint structures. Our goal is to enroll 140 individuals with symptomatic knee OA into a 2-year randomized placebo controlled clinical trial of vitamin D, 14,000 ID / week. Outcomes will include the WOMAC questionnaire (primary clinical), cartilage volume loss (primary pathological), physical function tests, SF-36 and whole organ knee MRI OA severity scores. Bone density, calcium homeostasis and knee alignment will be tested as intermediary variables. We will test effectiveness of vitamin D using cross-sectional time series regression models with first-order autoregressive disturbance adjusting for informative dropouts.