Trial of Vitamin D to Reduce Progression of Knee OA

描述(申请人提供)：有症状的膝骨性关节炎的发病率为240/100,000人年，是最常见的依赖于下肢任务的原因之一，尤其是在老年人中。它每年造成6800万天的工作损失，占年退休人数的5%以上。骨关节炎是关节置换最常见的原因，每年给社区造成数十亿美元的损失。目前尚无治疗骨性关节炎的有效药物。然而，制药业正试图开发延缓骨性关节炎进展的药物。如果有效，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，一种简单的非专利干预，可能在减缓OA进展方面有效。即使只是适度有效，它也可能在减轻开放式获取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补充剂作为一种治疗骨性关节炎的疾病修正疗法的有效性需要在严格的临床试验中进行测试。 由于放射学技术的限制，膝骨性关节炎的疾病修正试验一直很困难。然而，MRI已经成为一种有效、精确和可重复性的工具，用于测量软骨和关节结构的体积。 我们的目标是招募140名有症状的膝骨性关节炎患者参加为期两年的维生素D随机安慰剂对照临床试验，每周14,000次。结果将包括WOMAC问卷(主要临床)、软骨体积丢失(主要病理)、身体功能测试、SF-36和整个器官膝关节MRI OA严重程度评分。骨密度、钙稳态和膝关节对齐将作为中介变量进行测试。我们将使用带有一阶自回归干扰的横截面时间序列回归模型来检验维生素D的有效性。

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.