Weight loss, in vivo cartilage mechanics, and joint health

摘要 肥胖仍然是与发育和肥胖有关的最大和最易改变的风险因素之一 膝骨性关节炎的进展。虽然许多研究假设原发的病理 刺激是由于身体质量增加而导致的关节负荷增加，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，两者都 生物力学和炎症因素在肥胖诱导的骨性关节炎中起作用。这一点从办公自动化水平的提高中可见一斑 手和手腕等非承重关节的风险。 肥胖者可能表现出关节软骨成分和功能的变化，这些变化发生在 出现症状性骨性关节炎。例如，早期骨性关节炎软骨的变化包括蛋白多糖丢失和破坏。 两者都会降低软骨的弹性系数，从而降低其对载荷的变形反应。在……里面 与这一假设相一致，我们最近的试点数据表明，软骨应变对日常活动的反应 体重指数(BMI)高的参与者与体重正常的对照组相比，生活质量增加 体重指数。然而，目前尚不清楚软骨应变增加是否由于软骨成分的改变， 由于身体质量增加或多种因素的组合而导致的关节负荷增加。此外，目前还不清楚 这些软骨成分和机械功能的改变是否随着体重的减轻而可逆。因此， 我们的中心假设是肥胖会改变软骨的组成和机械功能。 随着体重的减轻，这些变化是可逆的。 为了解决这一假设，我们将使用磁共振成像(MRI)和高分辨率成像的新组合。 快速双平面摄影评价肥胖和体重减轻对活体软骨应变的影响 受控的功能活动(跑步机行走)。此外，我们将使用定量磁共振成像(T1-Rho和 T2标测)以评估肥胖和体重减轻是否改变了软骨的组成和组织 膝盖和手腕上的母体。此外，我们将调查软骨成分的变化是否 发生在手腕软骨中。这将确立与肥胖和减肥相关的系统性因素的作用， 因为手腕是一个非承重关节。软骨成分和机械功能的变化将是 与一组局部和系统生物标记物进行比较，以帮助建立临床适用的替代物 办公自动化进展的衡量标准。从拟议的研究中产生的数据对于确定 早期退行性改变的软骨成分和机械功能是否可以逆转。 归根结底，这些数据对于确定旨在预防和治疗骨性关节炎的临床干预的新目标至关重要。 治疗。

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.