Feasibility of a Novel Approach to Studying Early Knee Osteoarthritis: an Offspring Study.

 描述(申请人提供)：骨关节炎(OA)的公共卫生负担很大。这是最常见的关节炎形式，随着时间的推移，患病率会增加。与这种疾病相关的残疾和费用很高，有效的治疗方法是 少数，仅限于理疗、止痛，然后全关节置换术。因此，迫切需要更好地了解这种疾病的潜在病因，并确定有效的治疗方法。到目前为止，还没有确定可信的结构和改善症状的联合干预措施，可能是因为努力集中在错误的疾病时间框架上。提供有效干预的机会之窗可能只存在于开放式获取发展之前或开放式获取早期。然而，研究早期疾病患者是具有挑战性的，因为在这一群体中没有关于病例定义和症状评估的共识。一种创新的方法来解决这个问题，利用了膝盖骨关节炎的实质性遗传成分。我们将使用父母的表型来定义病例，在疾病已经确定的情况下，但我们的重点将放在他们的后代中的风险因素上，这些疾病要么还没有发生，要么还没有得到很好的确定。病例子代和对照子代可改变的危险因素的差异可以为预防疾病发生或早期疾病进展的干预措施提供信息。骨关节炎倡议(OAI)是一项 观察性研究，4796名参与者已经被跟踪8年，膝盖骨关节炎状态将可用。利用已经获得的有关疾病状态和现有OAI基础设施的数据来访问潜在参与者的父母，提供了一个独特的部署机会 这项拟议的研究。尽管研究参与者的后代具有研究较早的疾病时间框架的吸引力，但也有随之而来的挑战，包括在OAI框架内联系和招募潜在的后代参与者，同时尊重他们的 隐私和机密性。因此，在这项拨款申请中，我们建议进行一项试验性研究，以全面评估部署大规模子代研究的可行性，并获得初步数据，以便为R01申请资助此类研究提供参考。这项研究的两个目的是(1)评估在OAI中部署子代研究的可行性和(2)评估是否有可能使用已知的和探索性的子代危险因素来预测父母的骨性关节炎表型。获得初步数据，以便R01申请资助对OAI后代进行更大规模的研究。这项研究将通过实施一种新的探索性研究设计来开辟新的天地，这种疾病是一个主要的公共卫生问题，目前几乎没有有效的治疗方法。

 DESCRIPTION (provided by applicant): The public health burden of osteoarthritis (OA) is substantial. It is the most common form of arthritis, increasing in prevalence over time. The disability and cost related to the disease are high, and effective treatments for the condition are few, limited to physical therapy, analgesia, and then total joint replacement. Therefore, there is an urgent need to better understand the underlying etiology of this disease and to identify effective treatments for the condition. To date, no credible combined structure and symptom modifying intervention has been identified, perhaps because efforts have been focused on the wrong timeframe of disease. The window of opportunity to provide an effective intervention may only exist prior to the development of OA or early in the development of OA. Studying patients with early disease is challenging, however, because there is no consensus on case definition and symptom assessment in this group. An innovative approach to this problem, capitalizes on the substantial genetic component of knee OA. We will use the parental phenotype for case definition, where the disease is well-established, but our focus will be on risk factors in their offspring, where disease has either not yet occurred or is less well-established. Differences in modifiable risk factors of case versus control offspring could inform interventions that may prevent incident disease or progression of early disease. The Osteoarthritis Initiative (OAI) is an observational study where 4796 participants have been followed for 8 years and knee OA status will be available. Leveraging data already obtained about disease status and the existing OAI infrastructure to access parents of potential participants, provides a unique opportunity to deploy this proposed study. Although studying offspring of participants has the appeal of studying an earlier timeframe of disease, it also has its attendant challenges, including contacting and recruiting potential offspring participants within the framework of the OAI, while respecting their privacy and confidentiality. Therefore, in this grant application, we propose a pilot study to comprehensively assess feasibility of deploying a large scale offspring study and to obtain preliminary data to inform an R01 application to fund such a study. The two aims of this study are (1) to assess feasibility of deploying an offspring study within the OAI and (2) to assess whether it is possible to use known and exploratory offspring risk factors to predict the parental OA phenotype. Obtain preliminary data that would inform an R01 application to fund a larger scale study of the OAI Offspring. This study would break new ground by implementing a novel exploratory study design in a disease that is a major public health problem for which few effective treatments currently exist.