Factors influencing the evolution of knee osteoarthritis

描述(由申请人提供)： 这一职业发展奖的目标是通过正式的课程工作计划扩大候选人在临床研究方面的基础知识，帮助候选人融入学术研究社区，并提供她成功开发未来独立临床研究所需的经验和知识。本研究的目的是评估特发性骨关节炎(OA)发病的早期因素。关节动态负荷异常、肌肉无力和本体感觉缺陷已被独立研究，并与骨性关节炎有关。文献表明，这些因素可能是相互关联的；然而，没有一项研究将这些因素一起研究在骨性关节炎的发病机制中。研究人群的选择是基于候选人最近的研究结果：患有晚期单侧髋关节骨性关节炎的受试者更多地发生在对侧膝关节而不是同侧膝关节，并且这些受试者在髋关节置换前后对侧膝关节的动态关节负荷比同侧膝关节高。这是对45名有症状的早期单侧髋关节骨性关节炎患者和45名终末期单侧髋关节骨性关节炎患者的膝关节横断面评估。其具体目的是调查膝关节负荷、肌力和本体感觉之间的关系，确定同侧和对侧膝关节之间这些因素的不对称性，并评估单侧髋关节骨性关节炎早期和终末期的这些因素。受试者将接受面试、体检和X光检查。专门的测试将包括双X射线吸收法、步态分析、本体感觉评估和双膝肌肉力量测试。将对数据进行评估，以评估这些因素之间的具体联系，评估受试者膝盖之间的因素不对称，并证明单侧髋关节骨性关节炎的早期和终末期是否存在类似的不对称。这项研究的结果将显著影响我们对骨关节炎发病机制的理解，并可能为骨关节炎的治疗甚至一级预防干预提供新的途径。

DESCRIPTION (provided by applicant): The goals of this career development award are to expand the candidate's fundamental knowledge in clinical research through a formal course work program, help integrate the candidate into the academic research community, and to provide the experience and knowledge she will need to successfully develop future independent clinical investigations. This study's purpose is to evaluate early factors involved in the etiopathogenesis of idiopathic osteoarthritis (OA). Abnormal dynamic joint loading, muscle weakness, and proprioception deficits have been independently studied and linked to OA. The literature suggests that these factors may be interrelated; however, no single study has looked at these factors together in the pathogenesis of OA. The study population is chosen based upon the candidate's recent investigational findings: that subjects with advanced unilateral hip OA more commonly develop OA of the contralateral knee rather than the ipsilateral knee and that these subjects have higher dynamic joint loads at the contralateral knee relative to the ipsilateral knee before and after hip replacement. This is a cross-sectional evaluation of the knees of 45 subjects with symptomatic early unilateral hip OA and 45 subjects with endstage unilateral hip OA. The specific aims are to investigate relationships between loading, muscle strength, and proprioception of the knees, to identify asymmetries in these factors between the ipsilateral and contralateral knees, and to evaluate these factors in both early and endstages of unilateral hip OA. Subjects will undergo interview, physical exam, and radiography. Specialized testing will include dual x-ray absorptiometry, gait analysis, proprioception evaluation and muscle strength testing of both knees. The data will be evaluated to assess specific associations between the factors, to assess asymmetries in the factors between the subjects' knees, and to demonstrate whether similar asymmetries are present in both early and endstages of unilateral hip OA. The results from this investigation can significantly impact our understanding of neuromechanical mechanisms in the pathogenesis of OA and may provide new avenues for therapeutic and perhaps primary prevention intervention in OA.