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: 10536658
• 负责人: Louis E. DeFrate
• 金额: $ 35.42万
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10536658
• 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; Disease; Disease Progression; Exhibits; Gait; Guidelines; Hand; Health; Inflammation; Inflammatory; Intervention; Joints; Knee; Knee Osteoarthritis; Knowledge; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Modeling; Modulus; Obesity; Participant; Pathologic; Patient Self-Report; Persons; Physical Function; Play; Prevention; Proteoglycan; Relaxation; Research; Risk; Risk Factors; Role; Serum; Speed; Stimulus; Synovial Fluid; Targeted Research; Techniques; Testing; United States; Urine; Walking; Work; Wrist; adult obesity; articular cartilage; cartilage degradation; cartilage metabolism; clinical application; clinical diagnosis; clinically relevant; comparison control; high body mass index; improved; in vivo; joint loading; mechanical load; modifiable risk; new therapeutic target; novel; obese person; radiological imaging; response; 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 肥胖仍然是与发育和发育相关的最大且最可改变的风险因素之一。 膝骨关节炎（OA）的进展。虽然许多研究假设主要病理 刺激是由于体重增加而增加的关节负荷，关于其影响的数据有限 肥胖对膝关节软骨局部体内应变分布的影响。此外，最近的研究表明，两者 生物力学和炎症因子在肥胖引起的 OA 中发挥作用。 OA 升高证明了这一点 手和腕等非承重关节的风险。 肥胖受试者可能会在关节软骨成分和功能发生变化之前出现变化。 出现症状性 OA。例如，早期 OA 中软骨的变化包括蛋白多糖损失和破坏 胶原基质，两者都可以降低软骨模量，从而降低其对负载的变形响应。在 与这一假设相符，我们最近的试验数据表明，软骨因日常活动而应变 与体重指数正常的对照受试者相比，高体重指数 (BMI) 参与者的生活质量有所提高 体重指数。然而，尚不清楚软骨应变的增加是否是由于软骨成分的改变造成的。 由于体重增加或多种因素的组合而导致关节负荷增加。此外，还不清楚 软骨成分和机械功能的这些变化是否可以随着体重减轻而逆转。因此， 我们的中心假设是肥胖会改变软骨的成分和机械功能 并且这些变化随着体重减轻是可逆的。 为了解决这个假设，我们将使用磁共振成像（MRI）和高通量成像的新型组合。 加速双平面射线照相以评估肥胖和体重减轻对体内软骨应变的影响 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）评估肥胖和减肥是否改变软骨的组成和组织 膝盖和手腕的矩阵。此外，我们将研究软骨成分是否发生变化 发生于腕部软骨。这将确定与肥胖和减肥相关的全身因素的作用， 因为手腕是非承重关节。软骨成分和机械功能的变化将 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 进展的测量。拟议研究生成的数据对于确定 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 的临床干预新目标至关重要。 治疗。