Impact of Weight loss on Knee Joint Biochemical and Structural Degeneration

描述(申请人提供)：肥胖和骨关节炎(OA)密切相关；肥胖是骨关节炎的一个可改变的危险因素，减肥可能为疾病预防和减缓肥胖者的进展提供一种潜在的非侵入性疗法。然而，迄今为止，体重减轻对关节结构和软骨生化的影响，特别是在 疾病的早期阶段一直没有定论；研究受到短期随访的限制，重点放在疾病的晚期。这项拟议的研究利用了来自骨关节炎倡议的成像数据，这有助于结合骨性关节炎的纵向演变来评估早期疾病I期；利用这一独特而丰富的数据集，本研究旨在确定在8年的时间里，体重减轻对膝关节生化和形态变化的影响及其与体力活动和临床症状的关系。我们将使用磁共振T2弛豫时间测量，评估软骨胶原完整性和水分含量，以及半定量的形态MR分级。我们将对体重减轻组和对照组进行为期8年的全膝关节包括软骨、半月板、骨髓和关节间隙的全面检查。我们建议的项目有三个具体目标：(I)确定超重和肥胖的人在没有骨性关节炎(但有骨性关节炎的危险因素)以及有骨性关节炎的情况下，是否能够防止软骨生化和形态关节退变的发展和进展，并在8年内改善临床症状。(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化进展缓慢以及临床症状减轻有关。(Iii)确定体重减轻与退行性疾病进展较慢有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人的体重减轻是否可以防止骨性关节炎的发生，以及是否可以阻止疾病的进展。通过研究640名受试者，根据不同的体重减轻程度和不同的关节形态水平，这项建议将全面评估8年来对减肥反应的关节形态、软骨生化和临床症状的变化。从这项研究中，我们希望根据先前存在的退行性疾病的程度和初始体重，建立针对OA的特定对象减肥治疗指南。预防是目前对骨性关节炎的主要干预措施，我们坚信我们的研究将极大地有助于 精简和优化预防骨性关节炎的临床实践

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