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)是一种广泛存在的致残性疾病，病因不明，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。仅拇指功能丧失就会造成40%-50%的上肢损伤，因为它在几乎所有的抓握和处理任务中都起着核心作用。虽然最近的研究表明，遗传、BMI增加和环境因素(如手部使用)可能与拇指CMC骨关节炎的发生有关，但有强有力的经验和实验数据表明，生物力学改变在疾病中发挥核心作用，更重要的是在其治疗中发挥作用。CMC骨性关节炎在女性中的发病率远高于男性，女性关节表面较平，软骨接触面积较小，接触压力较高。对此的解释是，女性CMC关节的生物力学稳定性低于男性，因此增加了关节负荷改变和OA的发病和/或进展的风险。然而，在这一点上，目前还没有关于CMC关节生物力学在正常或OA患者中发表的研究，也没有任何关于疾病进展过程中关节生物力学的纵向研究。我们假设CMC关节松弛程度随年龄和性别的不同而不同，关节松弛程度将预测有症状的早期患者的OA进展，其中CMC关节松弛定义为关节运动学方向和/或幅度异常。这项研究旨在通过量化和比较老年女性(n=11，年龄45-75岁)拇指CMC生物力学的差异来生成活体拇指CMC生物力学的基础数据。年轻女性(n=11，年龄18-25岁)和男女(n=11，年龄18-25岁；n=11，年龄45-75岁)。使用横断面实验设计(目标1)，并采用纵向实验设计，确定CMC关节松弛是否与初次诊断后1.5年和3年的CMC OA进展呈正相关(N=80；45-75年。)最初表现为CMC疼痛和最低限度的骨性关节炎放射证据(Eaton I/II)(目标2)。Aim 1将提供迄今为止关于CMC关节在功能任务中的三维生物力学的第一个活体数据，这将深入了解生物力学在疾病中的作用，以及与男性相比女性骨性关节炎发病率高的原因。AIM 2将首次定量评估在该人群的早期骨关节炎进展过程中CMC关节发生的生物力学变化，并将为未来旨在评估关节生物力学改变与软骨退化之间的机制关系的研究提供基础。总之，这些研究将为合理设计旨在恢复、复制或替换复杂CMC关节的结构解剖的外科手术程序提供数据，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.