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.

摘要 肥胖仍然是最大和最可改变的危险因素之一， 膝关节骨关节炎（OA）的进展。虽然许多研究假设， 刺激是由于体重增加而导致的关节负荷增加，关于 肥胖对膝关节软骨中局部体内应变分布的影响。此外，最近的研究表明， 生物力学和炎症因子在肥胖诱导的OA中起作用。这可以通过OA升高来证明 非承重关节（如手和手腕）的风险。 肥胖受试者可能表现出关节软骨组成和功能的变化，这些变化发生在关节炎之前。 症状性OA发作。例如，早期OA中软骨的变化包括蛋白聚糖损失和破坏 的胶原基质，这两个可以降低软骨模量，从而其变形响应的负载。在 与这一假设一致，我们最近的试验数据表明，软骨应变响应于日常活动， 高体重指数（BMI）参与者的生活水平高于正常体重的对照组。 体重指数。然而，目前还不清楚增加的软骨应变是否是由于软骨成分的改变， 由于体重增加或多种因素的组合而导致的关节负荷增加。此外，尚不清楚 这些软骨成分和机械功能的变化是否随着体重减轻而可逆。因此，在本发明中， 我们的中心假设是肥胖改变了软骨的组成和机械功能 并且这些变化随着体重减轻是可逆的。 为了解决这一假设，我们将使用一种新的磁共振成像（MRI）和高- 速度双平面X线摄影，以评估肥胖和体重减轻对体内软骨应变的影响， 一种有控制的功能性活动（跑步机行走）。此外，我们将使用定量MR成像（T1-rho和 T2映射）以评估肥胖和体重减轻是否改变软骨的组成和组织 膝盖和手腕都有矩阵。此外，我们将研究软骨成分的改变是否 发生在腕关节软骨中。这将确立与肥胖和体重减轻有关的系统因素的作用， 因为手腕是非承重关节。软骨成分和机械功能的变化将是 与一组局部和全身生物标志物进行比较，以帮助建立临床适用的替代物 OA进展的指标。从拟议的研究中产生的数据对于确定 软骨成分和机械功能的早期退行性变化是否可以逆转。 最终，这些数据对于确定旨在预防OA的临床干预措施的新目标至关重要， 治疗