Thumb CMC Biomechanics and Early OA Progression

描述（由申请人提供）：拇指腕掌（CMC）骨关节炎（OA）是一种病因不明的广泛致残性疾病，女性比男性更常见。这种疾病影响了15%的30岁以上的成年人和三分之二的55岁以上的女性。由于上肢在几乎所有抓握和处理任务中的核心作用，仅拇指功能的丧失就造成上肢40%-50%的损伤。虽然最近的研究表明遗传学，BMI增加和环境因素（如手的使用）可能与拇指CMC OA的发展有关，但有强有力的经验和实验数据表明，生物力学的改变在疾病中起着核心作用，并且在其治疗中起着重要作用。CMC OA在女性中比男性更普遍，女性的关节表面更平坦，软骨接触面积更小，接触压力更高。对此的解释是，女性CMC关节的生物力学稳定性低于男性，因此关节负荷改变和OA发作和/或进展的风险增加。然而，在这一点上，没有发表的研究CMC关节生物力学在正常或OA影响的个人，也没有任何纵向研究关节生物力学的疾病进展。我们假设CMC关节松弛随年龄和性别而不同，并且关节松弛将预测有症状的早期患者的OA进展，其中CMC关节松弛定义为方向和/或幅度异常的关节运动学。本研究旨在通过量化和比较老年女性（n = 11，年龄45-75岁）的CMC生物力学差异，生成体内拇指CMC生物力学的基础数据。和年轻女性（n = 11，年龄18-25岁），女性和男性之间（n = 11，年龄18 - 25岁; n = 11，年龄45-75岁）。采用横断面实验设计（目标1），并采用纵向实验设计，确定CMC关节松弛是否与患者（N = 80; 45-75岁）初次诊断后1.5年和3年CMC OA进展呈正相关。最初表现为CMC疼痛和极轻微的OA影像学证据（Eaton I/II）（目标2）。目的1将提供迄今为止功能任务期间CMC关节的3-D生物力学的第一个体内数据，这应该可以深入了解生物力学在疾病中的作用，以及女性OA患病率高于男性的原因。目标2将首次对该人群早期OA进展期间CMC关节中发生的生物力学变化进行定量评估，并为旨在评价关节生物力学变化与软骨退化之间的机械关系的未来研究提供基础。总之，这些研究将为旨在恢复、重现或替换复杂CMC关节结构解剖的外科手术的合理设计提供数据，并为未来的随机对照试验和风险因素研究提供基线数据。

DESCRIPTION (provided by applicant): Thumb carpometacarpal (CMC) osteoarthritis (OA) is a widespread, disabling disease of undetermined etiology that is far more prevalent in woman than in men. The disease affects 15% of adults over age 30, and two-thirds of women over the age of 55. Loss of thumb function alone imparts a 40%-50% impairment to the upper extremity due to its central role in nearly all grasp and handling tasks. Although recent studies suggest genetics, increased BMI and environmental factors (such as hand use) are likely associated with the development of thumb CMC OA, there is strong empirical and experimental data indicating that altered biomechanics plays a central role in the disease, and, importantly in its treatment. CMC OA is far more prevalent in women than men, and women have flatter joint surfaces, smaller areas of cartilage contact, and higher contact pressures. The interpretation of this is that the CMC joints in women are less biomechanically stable than those in men, and consequently at increased risk for altered joint loading and the onset and/or progression of OA. At this point, however, there are no published studies of CMC joint biomechanics in normal or OA-affected individuals, nor are there any longitudinal studies of joint biomechanics as the disease progresses. We hypothesize CMC joint laxity differs with age and gender, and that joint laxity will predict OA progression in symptomatic, early-stage patients, where CMC joint laxity is defined as articular kinematics that are abnormal in direction and/or magnitude. This study is designed to generate foundational data on thumb CMC biomechanics in vivo by quantifying and comparing the differences in CMC biomechanics in older women (n = 11, age 45-75 yrs.) and younger women (n = 11, age 18-25 yrs.), and between women and men (n = 11, age 18 - 25 yrs; and n = 11, age 45-75 yrs.) using a cross-sectional experimental design (Aim 1), and, using a longitudinal experimental design, to determine if CMC joint laxity is positively associated with CMC OA progression 1.5 and 3 years after initial diagnosis in patients (N = 80; 45-75 yrs.) who initially present with CMC pain and minimal radiographic evidence of OA (Eaton I/II) (Aim 2). Aim 1 will provide the first in vivo data to date on 3-D biomechanics of the CMC joint during functional tasks, which should provide insight into the role of biomechanics in the disease, and reasons for the high prevalence of OA in women as compared to men. Aim 2 will provide the first quantitative assessment of the biomechanical changes that occur in the CMC joint during early OA progression in this population and will provide the foundation for future studies designed to evaluate the mechanistic relationship between altered joint biomechanics and cartilage degradation. Together, these studies will provide data for the rational design of surgical procedures designed to restore, reproduce, or replace the structural anatomy of the complex CMC joint, as well as baseline data for future randomized control trials and risk factor studies.