Weight loss, in vivo cartilage mechanics, and joint health

减肥、体内软骨力学和关节健康

• 批准号: 10091305
• 负责人: Louis E. DeFrate
• 金额: $ 34.36万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091305
• 关键词: 3-Dimensional; Activities of Daily Living; Address; Adult; Affect; Age; Biological Markers; Biomechanics; Body Weight decreased; Body mass index; Cartilage; Cartilage Matrix; Clinical; Collagen; Data; Degenerative polyarthritis; Development; Diagnostic radiologic examination; Disease; Disease Progression; Exhibits; Gait; Guidelines; Hand; Health; Inflammation; Inflammatory; Intervention; Joints; Knee; Knee Osteoarthritis; Knowledge; Magnetic Resonance Imaging; Measures; Mechanics; Modeling; Modulus; Obesity; Participant; Pathologic; Patient Self-Report; Physical Function; Play; Prevention; Proteoglycan; Relaxation; Research; Risk; Risk Factors; Role; Serum; Speed; Stimulus; Synovial Fluid; Targeted Research; Techniques; Testing; Time; United States; Urine; Walking; Work; Wrist; adult obesity; articular cartilage; cartilage degradation; cartilage metabolism; clinical Diagnosis; clinical application; clinically relevant; high body mass index; improved; in vivo; in vivo imaging; joint loading; mechanical load; modifiable risk; new therapeutic target; novel; obese person; response; rho; sex; specific biomarkers; symptomatic improvement; treadmill; weight loss intervention

Abstract Obesity remains one of the greatest and most modifiable risk factors associated with the development and progression of knee osteoarthritis (OA). While numerous studies hypothesize that the primary pathological stimulus is increased joint loading resulting from elevated body mass, there are limited data on the effects of obesity on local in vivo strain distributions in knee cartilage. Furthermore, recent studies suggest that both biomechanical and inflammatory factors play a role in obesity-induced OA. This is evidenced by elevated OA risk in non-weight bearing joints such as the hand and wrist. Obese subjects may exhibit changes in both articular cartilage composition and function that precede the onset of symptomatic OA. For example, changes to cartilage in early OA include proteoglycan loss and disruption of the collagen matrix, both of which can reduce cartilage modulus and thus its deformation response to load. In line with this hypothesis, our recent pilot data indicates that cartilage strains in response to activities of daily living are increased in participants with high body mass index (BMI) compared to control subjects with normal BMI. However, it is unclear whether increased cartilage strains are due to alterations in cartilage composition, increased joint loading resulting from elevated body mass, or a combination of factors. Furthermore, it is unclear whether these changes in cartilage composition and mechanical function are reversible with weight loss. Thus, our central hypothesis is that obesity alters both the composition and mechanical function of cartilage and that these changes are reversible with weight loss. To address this hypothesis, we will use a novel combination of magnetic resonance imaging (MRI) and high- speed biplanar radiography to evaluate the effects of obesity and weight loss on in vivo cartilage strains during a controlled functional activity (treadmill walking). Additionally, we will use quantitative MR imaging (T1-rho and T2 mapping) to evaluate whether obesity and weight loss alter the composition and organization of the cartilage matrix in both the knee and wrist. Furthermore, we will investigate whether alterations in cartilage composition occur in the wrist cartilage. This will establish the role of systemic factors that relate to obesity and weight loss, as the wrist is a non-weight bearing joint. Changes in cartilage composition and mechanical function will be compared to a panel of local and systemic biomarkers in order to help establish clinically applicable surrogate measures of OA progression. The data generated from the proposed research are crucial for determining whether early degenerative changes in cartilage composition and mechanical function can be reversed. Ultimately, these data are critical to identifying new targets for clinical interventions aimed at OA prevention and treatment.

抽象的 肥胖仍然是与开发相关的最大，最可修改的危险因素之一 膝盖骨关节炎（OA）的进展。众多研究假设主要病理 刺激是由于体重升高而增加的关节负荷，关于 膝盖软骨中局部体内菌株分布的肥胖。此外，最近的研究表明 生物力学和炎症因子在肥胖引起的OA中起作用。升高的OA可以证明这一点 在非重量轴承关节（如手腕和腕部）中的风险。 肥胖受试者可能在关节软骨组成和功能之前都显示出变化 有症状的OA发作。例如，OA早期软骨的变化包括蛋白聚糖损失和破坏 胶原蛋白基质（两者都可以减少软骨模量），从而减少其对负载的变形响应。在 与这一假设相吻合，我们最近的试点数据表明，针对每日活动的软骨菌株 与正常的对照组相比，高体重指数（BMI）的参与者的生活增加 BMI。但是，尚不清楚软骨菌株增加是否是由于软骨组成的改变， 增加体重升高或因素组合导致关节负荷增加。此外，还不清楚 这些软骨组成和机械功能的变化是否可以通过减肥而可逆。因此， 我们的中心假设是肥胖可以改变软骨的组成和机械功能 这些变化随体重减轻而可逆。 为了解决这一假设，我们将使用磁共振成像（MRI）和高级的新型组合 快速双流射线照相，以评估肥胖和体重减轻对体内软骨菌株的影响 受控的功能活动（跑步机行走）。此外，我们将使用定量MR成像（T1-RHO和 T2映射）评估肥胖和体重减轻是否改变了软骨的组成和组织 膝盖和手腕的矩阵。此外，我们将研究软骨组成的改变是否 发生在手腕软骨中。这将确定与肥胖和体重减轻有关的系统因素的作用， 由于手腕是一个非重量轴承关节。软骨组成和机械功能的变化将是 与本地和系统的生物标志物相比，为了帮助建立临床适用的替代物 OA进展的度量。从拟议的研究中产生的数据对于确定 是否可以逆转软骨组成和机械功能的早期退行性变化。 最终，这些数据对于确定针对预防OA和的临床干预措施的新目标至关重要 治疗。