ROLE OF NONSTEROIDAL ANTIINFLAMMATORY AGENTS IN OUTCOME OF OA

骨关节炎是人类最常见的疾病。它是最多的 在这个国家导致残疾的共同原因，并有巨大的社会经济 冲击力。骨性关节炎是一种关节软骨退行性疾病。非- 类固醇抗炎药(NSAIDs)是最受欢迎的药物 临床上用于治疗关节疼痛和炎症， 与骨质疏松症有关。非甾体类抗炎药会阻碍酶的产生 环氧合酶导致炎症的产生减少 前列腺素E_2。尽管非甾体抗炎药对疼痛控制很有用， 最近的研究已经开始产生数据，需要临床医生重新 评估我们治疗骨性关节炎的策略。例如，当消炎痛 用于髋关节骨性关节炎患者，他们需要关节置换 时间减半，放射学进展速度是 患者接受弱PGE2抑制剂氮丙酮的治疗。其他 研究还没有发现非类固醇抗炎药比对乙酰氨基酚更好地治疗 膝骨性关节炎疼痛的治疗。这种相对缺乏效力，以及 疾病加速发展的可能性，加上已知的 这些药物的胃肠道风险，特别是对老年人， 使我们重新评估非类固醇抗炎药作为治疗 骨性关节炎。我们基于非甾体抗炎药治疗这种疾病的主要方法可能是 导致不必要的成本、不必要的毒性和加速 残疾。 这些数据使我们可以假设，非甾体抗炎药通过抑制疼痛和 骨关节炎关节的炎症，可能导致或鼓励骨关节炎患者 过度使用损坏的关节，导致关节加速退化和 在更早的时间进行关节置换，或者，替代地，那种治疗 非甾体抗炎药可能通过改变软骨而加速关节损伤 新陈代谢和抑制关节愈合。我们进一步假设 非甾体类抗炎药的抗炎治疗导致毒性反应 合并症增加，医疗服务利用率更高 骨性关节炎的止痛药使用。 我们建议的研究的具体目标是：(1)确定非 非甾体抗炎药的类固醇抗炎药物治疗加速关节 与止痛药相比，退化性疾病。(2)确定非- 类固醇抗炎药物治疗导致更大的共病 以及更高的医疗成本和利用率 止痛药。为了实现这些具体目标，我们将 随机选择200名膝关节和髋关节骨关节炎受试者，由Kellgren和 劳伦斯2级或3级X射线，目前正在服用非甾体抗炎药， 他们目前的剂量或对乙酰氨基酚不超过4000毫克/天，持续一段时间 四年了。主要的结果指标将是X线片的比率 两组的进展、疼痛和残疾情况。次要结果 变量将包括医疗服务利用率、关节连接时间 替代药物，以及药物副作用档案。我们将分别- 确定并描述这些临床、人口学和放射学 预测每组加速进展的变量 多变量分析。通过这些方法，我们将确定长期的 非甾体抗炎药与止痛药治疗慢性阻塞性肺疾病的疗效比较 膝关节和髋关节的临床骨性关节炎。这一信息对于 改善疾病的结局，这是导致 老年人的残疾。

Osteoarthritis (OA) is the most common disease of mankind. It is the most common cause of disability in this country and has enormous socioeconomic impact. OA is a disease of articular cartilage degeneration. Non- steroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used in clinical practice to treat the joint pain and inflammation that is associated with OA. NSAIDs block the production of the enzyme cyclooxygenase resulting in a decreased production -of inflammatory prostaglandins, PGE2. Although NSAIDs are useful for pain management, recent studies have begun to produce data that require clinicians to re- evaluate our treatment strategy for OA. For example, when indomethacin was used for patients with hip OA, they required joint replacements in half the time and radiographic progression was twice as fast as when patients were treated with a weak PGE2 inhibitor, azapropazone. Other studies have not found NSAIDs to be better than acetaminophen for the treatment of painful knee OA. This relative lack of efficacy, and possibility of accelerated disease progression, coupled with the known gastrointestinal risks of these medications, especially to the elderly, have led us to re-evaluate NSAIDs as the first line medical therapy for osteoarthritis. Our dominant NSAID based approach to this disease may be resulting in unnecessary costs, unnecessary toxicity, and accelerated disability. These data allow us to hypothesize that NSAIDs, by inhibiting pain and inflammation in OA joints, may cause or encourage patients with OA to overuse damaged joints, resulting in accelerated joint degeneration and joint replacements at an earlier time or, alternatively, that treatment with NSAIDs may act to accelerate joint damage by altering cartilage metabolism and inhibiting joint healing. We further hypothesize that anti-inflammatory therapy with NSAIDs results in toxicities that lead to increased comorbidity and higher medical care utilization compared to analgesic use for OA. The specific aims of our proposed study are (1) to determine if non- steroidal anti-inflammatory drug therapy of NSAIDs accelerates joint degeneration compared to analgesic medications. (2) to determine if non- steroidal anti-inflammatory drug therapy results in greater comorbidity and higher medical care costs and utilization compared to simple analgesic medication. To accomplish these specific aims, we will randomize 200 knee and 200 hip OA subjects, defined by a Kellgren and Lawrence x-ray grade of 2 or 3, currently on NSAIDs, to either NSAIDs at their current dose or acetaminophen up to 4000 mg/day, for a period of four years. Primary outcome measures will be the rate of radiographic progression, pain and disability in the two groups. Secondary outcome variables will include medical care utilization, time to joint replacements, and medication side effect profiles. We will separately- identify and describe those clinical, demographic, and radiographic variables which predict accelerated progression in each group by multivariate analyses. By these methods, we will determine the long-term outcome of NSAID therapy versus analgesic therapy for the treatment of clinical OA of the knee and hip. This information is critical to improving the outcome of the disease that is the principal cause of disability in the elderly.