Impact of Weight loss on Knee Joint Biochemical and Structural Degeneration

描述（由申请人提供）：肥胖和骨关节炎（OA）密切相关;肥胖是OA的一个可改变的风险因素，减肥可能为肥胖个体的疾病预防和减缓进展提供潜在的非侵入性治疗。然而，到目前为止，体重减轻对关节结构和软骨生物化学的影响，特别是在 疾病的早期阶段，一直没有定论;研究一直受到短期随访的限制，并集中在先进的疾病阶段。拟议的研究利用骨关节炎倡议的成像数据，这有助于评估早期疾病阶段和OA的纵向演变;使用这个独特而丰富的数据集，本研究旨在确定体重减轻对膝关节生化和形态学变化的影响，以及它们与体力活动和临床症状的关系，为期8年。我们将使用MRI T2弛豫时间测量，评估软骨胶原完整性和含水量以及半定量形态MR分级。我们将全面研究整个膝关节，包括软骨、半月板、骨髓和关节间隙，研究对象为体重减轻的受试者和体重不变的对照组，研究时间超过8年。我们提出的项目有3个具体目标：（I）确定体重减轻是否在超重和肥胖的个人没有OA（但OA的风险因素）以及与OA防止软骨生化和形态关节退行性变的发展和进展，并改善临床症状超过8年。(II)确定哪些减肥方法（改变饮食、增加体力活动、手术）与结构和生化关节退行性变进展缓慢以及临床症状缓解相关。(III)确定体重减轻与退行性疾病进展缓慢相关的患者的基线特征。拟议的项目将首次评估超重和肥胖个体的体重减轻是否可以预防OA的发作，以及是否可以阻止疾病的进展。通过研究640名受试者，按不同程度的体重减轻和不同水平的关节形态分层，该提案将全面评估关节形态，软骨生物化学和临床症状的变化，以应对8年以上的体重减轻。从这项研究中，我们期望建立针对OA的体重减轻治疗的受试者特定指南，该指南取决于既存退行性疾病的程度和初始体重。预防是目前OA的关键干预措施，我们坚信我们的研究将大大有助于 简化和优化OA预防的临床实践

DESCRIPTION (provided by applicant): Obesity and osteoarthritis (OA) are intimately related; obesity is a modifiable risk factor for OA and weight loss may offer a potential non-invasive therapy for disease prevention and for slowing progression in obese individuals. To date, however, the effects of weight loss on joint structure and cartilage biochemistry, in particular in the early stages of disease, have been inconclusive; studies have been limited by short-term follow-up and have focused on advanced disease stages. The proposed study utilizes imaging data from the Osteoarthritis Initiative, which facilitates the assessment of early disease stages i conjunction with the longitudinal evolution of OA; using this unique and rich dataset, this study aims to determine the impact of weight loss on the biochemical and morphologic changes at the knee joint and their relationship with physical activity and clinical symptoms over a period of 8 years. We will use MRI T2 relaxation time measurements, which assess cartilage collagen integrity and water content as well as semi-quantitative morphological MR grading. We will comprehensively investigate the whole knee joint including the cartilage, meniscus, bone marrow, and joint space in subjects with weight loss and controls with constant weight over 8 years. Our proposed project has 3 Specific Aims: (I) To determine whether weight loss in overweight and obese individuals without OA (but risk factors for OA) as well as with OA protects against the development and progression of cartilage biochemical and morphological joint degeneration, and improves clinical symptoms over 8 years. (II) To determine which methods for weight loss (changes in diet, increased physical activity, surgery) are associated with slower progression of structural and biochemical joint degeneration as well as alleviation of clinical symptoms. (III) To identify baseline characteristics of patients whose weight loss is associated with slower progression of degenerative disease. The proposed project will, for the first time, assess whether weight loss in overweight and obese individuals may prevent the onset of OA and whether it may halt the progression of disease. By studying 640 subjects stratified by varied magnitudes of weight loss and varied levels of joint morphology, this proposal would comprehensively assess changes in joint morphology, cartilage biochemistry, and clinical symptoms in response to weight loss over 8 years. From this study, we expect to establish subject-specific guidelines for weight loss therapy in response to OA that are contingent upon the degree of pre-existing degenerative disease and initial weight. Prevention is currently the key intervention in OA and we strongly believe that our study will greatly contribute to streamlining and optimizing clinical practice of OA prevention