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

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 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.