Quantifying the Mechanism and Impact of Hip Extensor Muscle Dysfunction During Aerobic Exercise in Hip Osteoarthritis

项目摘要/摘要 髋关节骨关节炎(OA)影响大约25%的45岁以上人群。当前 保守治疗包括以运动为基础的计划，但这些干预措施在减少 髋关节骨关节炎相关的临床和功能异常。这些锻炼计划的一个限制是缺乏 用于建立这些治疗范例的证据，这导致这些方案在#年无效 治疗髋关节骨性关节炎。目前用于为髋关节骨性关节炎人群提供锻炼计划的实验方案 在测量髋关节肌肉功能障碍方面缺乏精确性。因此，有必要建立一个 可以精确测量髋关节肌肉功能障碍的实验平台。新奇的实验 此应用程序中提出的平台将能够准确评估髋部肌肉功能障碍，并将提供 拥有所需证据的临床医生为保守派制定有效的多学科锻炼计划 症状性髋关节骨关节炎的治疗。 K01奖的首席研究员(PI)将开发一个新颖的、多通道的实验平台 这将准确地衡量髋关节伸肌功能障碍对有症状的髋关节骨性关节炎患者的影响。 PI将利用新的成像技术和肌肉扭矩发展的评估来评估 症状性髋关节骨性关节炎患者髋关节伸展功能障碍的病理机制相应的影响 在有氧运动(机械负荷测试)中髋关节伸展功能障碍的情况将在以下患者中进行评估 症状性髋关节骨关节炎。将使用肌肉骨骼模拟和基于血清的软骨健康生物标记物 为了量化髋关节接触力和全身软骨周转/合成的变化， 分别在机械应力测试过程中。这些研究结果将被用来确定 臀大肌纤维化和髋伸肌力矩发展速度随髋关节负荷的变化， 在有症状的髋关节骨性关节炎人群中，软骨健康和自我报告的髋关节疼痛。完成此K01后 项目，申请者将拥有在一个 评估髋关节伸展功能障碍与髋关节骨性关节炎疾病纵向关系的大规模基础 在后续的R01应用程序中取得进展。 PI制定了强有力的衰老、肌肉成像、肌肉生理学和 生化生物标志物。该协会成立了一个多元化的咨询委员会，在老龄化、体能方面具有专业知识 治疗、生物力学、肌肉生理学、骨关节炎的运动、骨关节炎的生物标志物和生物统计学。本K01- 该奖项将为PI提供完成该项目目标所需的培训和资源，并将 带领PI走向成功的职业生涯，成为与衰老相关的研究的独立调查员。

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.