Thumb CMC Biomechanics and Early OA Progression

描述（由申请人提供）：拇指腕掌骨关节炎（CMC）是一种广泛的致残疾病，病因不明，女性比男性更普遍。30岁以上的成年人中有15%患有此病，55岁以上的女性中有三分之二患有此病。由于拇指在几乎所有抓取和处理任务中都起着核心作用，因此仅大拇指功能的丧失就会对上肢造成40%-50%的损害。尽管最近的研究表明，遗传、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，改变的生物力学在该疾病中起着核心作用，并且在其治疗中发挥重要作用。CMC骨性关节炎在女性中的发病率远高于男性，女性关节表面更平坦，软骨接触面积更小，接触压力更高。对这一现象的解释是，女性CMC关节的生物力学稳定性不如男性，因此关节负荷改变以及OA发病和/或进展的风险增加。然而，目前还没有发表的关于正常或oa患者CMC关节生物力学的研究，也没有任何随疾病进展的关节生物力学的纵向研究。我们假设CMC关节松弛度随年龄和性别的不同而不同，关节松弛度可以预测有症状的早期OA患者的进展，其中CMC关节松弛被定义为关节运动方向和/或大小异常。本研究旨在通过量化和比较老年女性（n = 11，年龄45-75岁）和年轻女性（n = 11，年龄18-25岁）以及女性和男性(n = 11，年龄18-25岁；（n = 11，年龄45-75岁），采用横断实验设计（Aim 1），并采用纵向实验设计，确定最初表现为CMC疼痛且骨性关节炎放射学证据最小（Eaton I/II）的患者（n = 80, 45-75岁）在初次诊断后1.5年和3年CMC关节松弛是否与CMC骨性关节炎进展呈正相关（Aim 2）。目的1将提供迄今为止第一个关于CMC关节在功能任务期间的三维生物力学的体内数据，这将有助于深入了解生物力学在疾病中的作用，以及与男性相比，女性OA患病率高的原因。目的2将首次定量评估该人群早期OA进展期间CMC关节发生的生物力学变化，并为未来的研究提供基础，旨在评估改变的关节生物力学与软骨退化之间的机制关系。总之，这些研究将为合理设计修复、复制或替代复杂CMC关节结构解剖的外科手术提供数据，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.