ROLE OF NONSTEROIDAL ANTIINFLAMMATORY AGENTS IN OUTCOME OF OA

骨关节炎（OA）是人类最常见的疾病。它是最 残疾的常见原因，并有巨大的社会经济 冲击OA是一种关节软骨退行性疾病。非 甾体抗炎药（NSAIDs）是最常用的药物 用于临床治疗关节疼痛和炎症， 与OA有关。非甾体类抗炎药阻断酶的产生 环氧合酶导致炎症的产生减少 前列腺素PGE 2虽然NSAID对疼痛管理有用， 最近的研究已经开始产生需要临床医生重新评估的数据， 评估我们的OA治疗策略。例如，当吲哚美辛 用于髋关节OA患者，他们需要关节置换术， 一半的时间和放射学进展是两倍的速度时， 患者用弱PGE 2抑制剂阿扎丙帕酮治疗。其他 研究还没有发现NSAID比对乙酰氨基酚更好， 治疗疼痛的膝关节OA。这种相对缺乏功效， 可能加速疾病进展，加上已知的 这些药物的胃肠道风险，特别是对老年人， 这促使我们重新评估NSAID作为一线药物治疗， 骨关节炎我们对这种疾病的主要基于NSAID的方法可能是 导致不必要的成本、不必要的毒性和加速的 残疾。 这些数据使我们能够假设，非甾体抗炎药，通过抑制疼痛， OA关节炎症，可能导致或鼓励OA患者 过度使用受损的关节，导致关节加速退化， 在较早时间进行关节置换，或者， 可能会通过改变软骨来加速关节损伤 代谢和抑制关节愈合。我们进一步假设， NSAID的抗炎治疗导致毒性， 与对照组相比， 用于OA的止痛剂。 我们建议的研究的具体目标是：（1）确定非- 甾体抗炎药治疗非甾体抗炎药加速关节炎 与止痛药相比，(2)以确定非- 甾体抗炎药治疗导致更大的并发症 和更高的医疗保健成本和利用率相比， 止痛药为了实现这些具体目标，我们将 随机分配200名膝关节和200名髋关节OA受试者，由Kellgren和 Lawrence X线2级或3级，目前正在服用NSAID， 他们目前的剂量或对乙酰氨基酚高达4000毫克/天，一段时间， 四年主要结局指标为放射学检查 两组的进展、疼痛和残疾。次要结局 变量将包括医疗服务利用率、关节连接时间 替代品和药物副作用概况。我们将分别- 确定并描述那些临床、人口统计学和影像学检查 预测各组加速进展的变量， 多变量分析通过这些方法，我们将确定长期 非甾体类抗炎药治疗与镇痛药治疗的结果 膝关节和髋关节的临床OA。这些信息对于 改善疾病的结果，这是主要原因， 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.