Thumb CMC Biomechanics and Early OA Progression

拇指腕掌（CMC）骨关节炎（OA）是一种广泛的致残性疾病， 女性比男性更普遍。这种疾病影响了15%的30岁以上的成年人，三分之二的30岁以上的妇女。 55岁虽然骨关节炎的病理生理学被认为是多因素的， 运动学和改变的软骨接触被认为是通过产生 非生理接触应力，这反过来又导致软骨细胞紊乱，坏死，和软骨 降解然而，在这一点上，只有有限的数据拇指CMC关节生物力学正常或 OA影响的个人，并没有纵向研究关节生物力学的疾病进展。 因此，本研究更广泛的长期目标是探索生物力学的作用， 形态学在基底拇指关节骨关节炎，努力确定生物力学标志物的启动 和疾病的进展，最终将改善预后和治疗。的具体目标 本申请中概述的工作是在现有的拇指队列中纵向跟踪疾病进展 CMC OA患者，在4.5年和6年随访时获得生物力学、影像学和临床数据， 我们的创新技术，作为基线（0年），1.5和3年收集的数据的后续，在 上一个融资周期。 评价生物力学和形态学在基底拇指关节骨关节炎中的作用， 实现两个具体目标。目标1将评价关节不稳定性作为拇指CMC的潜在标志 在患有早期CMC OA（疼痛但无疼痛）的现有女性和男性队列中， 大体放射学改变）。目标2将确定女性拇指CMC OA进展率是否 如果疾病进展的任何差异率与相应的 关节不稳定和骨形状变化的差异。这两个目标将通过长期随访进行评估， 85例早期OA患者。创新的生物力学标志物和标准化的临床结局指标将成为 用于解决每个目标中概述的假设。在每次随访访视时（第4.5年和第6年），CMC关节 运动（关节运动学）和不稳定性在三个高要求的任务将评估与我们的国家的最先进的 基于计算机断层扫描的无标记骨配准技术。手腕/手指导的历史和 还将进行体格检查，以及拇指运动范围和力量的定量评估， 三组标准化患者报告的功能评估和平片，使用相同的 上一个供资周期使用的议定书和调查工具。这一提议的意义在于 长期纵向研究和CMC OA进展的生物力学标志物的鉴定。这 信息对于未来的基础和临床研究以及合理设计创新药物至关重要。 预防和治疗战略。

Thumb carpometacarpal (CMC) osteoarthritis (OA) is a widespread, disabling disease that is far more prevalent in woman than men. The disease affects 15% of adults over age 30, and two-thirds of women over the age of 55. While the pathophysiology of osteoarthritis is considered to be multifactorial, abnormal joint kinematics and altered cartilage contact are believed to trigger and sustain the disease via the production of non-physiologic contact stresses, which in turn lead to chondrocyte derangement, necrosis, and cartilage degradation. However, at this point there is only limited data on thumb CMC joint biomechanics in normal or OA-affected individuals, and there are no longitudinal studies of joint biomechanics as the disease progresses. Accordingly, the broader, long-term objective of this study is to explore the role of biomechanics and morphology in basilar thumb joint osteoarthritis in an effort to identify biomechanical markers for the initiation and progression of the disease that will ultimately improve prognosis and treatment. The specific objective of the work outlined in this application is to follow disease progression longitudinally in a existing cohort of thumb CMC OA patients, acquiring biomechanical, radiographic, and clinical data at 4.5- and 6-year follow-ups using our innovative techniques, as a follow-on to data collected at baseline (0 yr), 1.5 and 3 years, during the previous funding cycle. Evaluation of the role of biomechanics and morphology in basilar thumb joint osteoarthritis will be accomplished via two specific aims. Aim 1 will evaluate joint instability as a potential marker for thumb CMC OA progression in an existing cohort of women and men who presented with early stage CMC OA (pain but no gross radiographic changes). Aim 2 will determine if the rate of thumb CMC OA progression in women is greater than in men, and if any differential rate of disease progression is associated with corresponding differences in joint instability and bone shape changes. Both aims will be evaluated via long-term follow-up of 85 early OA patients. Innovative biomechanical markers and standardized clinical outcome measures will be used to address the hypotheses outlined in each aim. At each follow-up visit (years 4.5 and 6) CMC joint motion (arthrokinematics) and instability during three high-demand tasks will be assessed with our state-of-art computed tomography-based markerless bone registration techniques. Wrist/hand-directed histories and physical exams will also be obtained, as will quantitative assessments of thumb range of motion and strength, three sets of standardized patient-reported functional assessments, and plain radiographs, using the same protocols and survey instruments used during the previous funding cycle. The significance of this proposal is the long-term longitudinal study and the identification of biomechanical markers for CMC OA progression. This information is crucial for future basic and clinical research studies and for the rational design of innovative new strategies for prevention and treatment.