Project Summary/Abstract Hip osteoarthritis (OA) impacts approximately 25% of the population over the age of 45 years. Current conservative treatments include exercise-based programs yet these interventions are ineffective in reducing hip OA-related clinical and functional abnormalities. One limitation of these exercise programs is the lack of evidence used to establish these treatment paradigms, which leads to the ineffectiveness of these programs in treating hip OA. Current experimental protocols used to inform exercise programs for the hip OA population lack precision in measuring hip joint muscular dysfunction. Therefore, there is a need to establish an experimental platform that can precisely measure hip joint muscular dysfunction. The novel experimental platform proposed in this application will be able to precisely assess hip muscle dysfunction and will provide clinicians with the evidence needed to develop effective multi-disciplinary, exercise programs for conservative treatment of symptomatic hip OA. The principal investigator (PI) of this K01 award will develop a novel, multi-modal experimental platform that will precisely measure the effects of hip extensor muscle dysfunction in patients with symptomatic hip OA. The PI will utilize novel imaging techniques and assessment of muscle torque development to assess the pathomechanism of hip extensor dysfunction in patients with symptomatic hip OA. The corresponding effects of hip extensor dysfunction during aerobic exercise (mechanical stress test) will be assessed in patients with symptomatic hip OA. Musculoskeletal simulations and serum-based biomarkers of cartilage health will be used to quantify the changes that occur in hip joint contact forces and systemic cartilage turnover/synthesis, respectively, during the mechanical stress test. These study results will be used to determine the relationship of gluteus maximus muscle fibrosis and hip extensor rate of torque development with changes in hip loading, cartilage health and self-reported hip pain in the symptomatic hip OA population. Upon completion of this K01 project, the applicant will possess the knowledge needed to implement this novel experimental platform on a large scale basis to assess the longitudinal relationship between hip extensor dysfunction with hip OA disease progression in the subsequent R01 application. The PI has developed a strong training plan in aging, muscle-imaging, muscle-physiology and biochemical biomarkers. The PI has established a diverse advisory committee with expertise in aging, physical therapy, biomechanics, muscle-physiology, exercise for OA, biomarkers of OA and biostatistics. This K01- award will provide the PI with the training and resources needed to accomplish the goals of this project and will lead the PI towards a successful career as an independent investigator in aging-related research.

Project Narrative Exercise-based programs for hip osteoarthritis (OA) lack scientific evidence and are ineffective in conservatively treating hip OA. Current experimental protocols are unable to precisely assess the underlying pathomechanism of hip extensor dysfunction that is associated with abnormal hip joint mechanics, hip pain and cartilage breakdown during exercise in hip OA. This study will lead to the development of a novel, multi-modal experimental platform, consisting of magnetic resonance imaging, muscle-function assessment, musculoskeletal simulations and biochemical biomarkers, which will be used to assess the pathomechanism and corresponding effects of hip extensor dysfunction during aerobic exercise in patients with symptomatic hip OA.