Impact of Weight loss on Knee Joint Biochemical and Structural Degeneration

减肥对膝关节生化和结构退化的影响

• 批准号: 8760726
• 负责人: THOMAS M LINK
• 金额: $ 31.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8760726
• 关键词: Address; Affect; Age; Biochemical; Biochemistry; Biomechanics; Body Weight Changes; Body Weight decreased; Bone Marrow; Cartilage; Cartilage Matrix; Characteristics; Clinical; Clinical Trials; Collagen; Data; Data Set; Degenerative Disorder; Degenerative polyarthritis; Development; Diet; Disease; Disease Progression; Evolution; Gait; Gender; Guidelines; Health; Heterogeneity; Image; Individual; Inflammation; Intervention; Investigation; Joints; Knee; Knee Osteoarthritis; Knee joint; Lead; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Measurement; Mediating; Meniscus structure of joint; Methods; Morphology; Obesity; Operative Surgical Procedures; Outcome Measure; Overweight; Pain; Participant; Patients; Pattern; Physical Function; Physical activity; Prevalence; Prevention; Public Health; Questionnaires; Recommendation; Relaxation; Risk; Risk Factors; SF-12; Staging; Stress; Structure; Symptoms; Techniques; Time; Treatment Efficacy; Visit; Water; Weight; Weight maintenance regimen; advanced disease; base; clinical practice; cohort; demographics; design; disorder prevention; effective therapy; follow-up; improved; insight; joint loading; knee pain; modifiable risk; muscle strength; novel; prevent; response

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

描述（由申请人提供）：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，迄今为止，减肥对关节结构和软骨生物化学的影响，特别是在 疾病的早​​期阶段尚无定论；研究受到短期随访的限制，并且集中于晚期疾病阶段。拟议的研究利用了骨关节炎倡议的成像数据，这有助于评估早期疾病阶段以及 OA 的纵向演变；利用这一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变化的影响及其与 8 年期间身体活动和临床症状的关系。我们将使用 MRI T2 弛豫时间测量来评估软骨胶原完整性和含水量以及半定量形态学 MR 分级。我们将对体重减轻的受试者和体重恒定的对照组8年以上的整个膝关节进行全面检查，包括软骨、半月板、骨髓和关节间隙。我们提出的项目有 3 个具体目标：(I) 确定没有 OA（但有 OA 危险因素）和有 OA 的超重和肥胖个体的体重减轻是否可以防止软骨生化和形态学退化的发生和进展，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）与减缓结构和生化关节退化的进展以及减轻临床症状相关。 (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减肥是否可以预防骨关节炎的发作以及是否可以阻止疾病的进展。通过研究按不同体重减轻程度和不同水平的关节形态分层的 640 名受试者，该提案将全面评估 8 年来体重减轻引起的关节形态、软骨生物化学和临床症状的变化。通过这项研究，我们希望根据先前存在的退行性疾病的程度和初始体重，针对 OA 制定针对特定受试者的减肥治疗指南。预防是目前 OA 的关键干预措施，我们坚信我们的研究将做出巨大贡献 简化和优化 OA 预防的临床实践