Effect of Osseointegrated Prostheses on the Pathogenesis of Hip Osteoarthritis in Patients with Lower Limb Loss

项目总结 这项建议的首要目标是确定经股骨集成型假体是否有 对髋关节骨关节炎(OA)的病因学有积极影响。以下两个导致残疾的主要原因 经股截肢是一种慢性皮肤病变，原因是眼窝配合不良(如溃疡)和骨关节炎，原因是 习惯性地改变关节负荷。骨整合假体是治疗牙槽窝的一种新的临床干预方法 通过骨锚固植入物将假体直接安装到残肢上， 提供从地面到残肢的更规范的载荷传递。这项提案将决定是否 这一改进的负荷传递在髋关节骨性关节炎的发病机制中具有不同于Socket的积极作用 假肢。这将通过纵向研究设计来完成，该设计将比较最常见的 在两个时间点之间的两个时间点(基线和12个月)导致骨关节炎进展的生物力学病因 组(使用骨整合假体的患者和成功使用传统牙槽的患者 假体)。在目标1中，我们将使用脂肪分数定量磁性来量化双侧髋部肌肉的质量 磁共振成像(MRI)。使用这些图像，我们将量化3D肌肉体积和脂肪渗透程度 双侧臀部肌肉系统。这将阐明已知的萎缩和由于停用而导致的不良成分是否 眼窝假体可以在假体后翻转，这两种假体都可以进展为骨性关节炎。 骨整合。在目标2中，我们将使用运动捕捉和一个 受试者特定的肌肉骨骼接触模型。因为软骨负荷的改变是一个主要的激发因素 在骨性关节炎的发生和发展中的因素，这些结果将决定软骨力学是否在 骨性融合后的日常生活能力。尽管肌肉成分和软骨力学 骨性关节炎发生的病因，我们试图评估骨整合在临床进展中的作用。 对于办公自动化来说。因此，在目标3中，我们将使用T2定量MRI来量化软骨健康，这是目前最多的 评估体内早期骨关节炎变化的灵敏方法学。最终，我们寻求使用我们的多域 更好地告知旨在改善骨整合后结果的有针对性的干预措施的方法。 候选人的首要职业目标是利用基于工程的工具更好地阐明 可用于改善针对性干预措施的继发性疼痛状况的机制。这项建议 在应聘者当前专业知识的基础上，提供新的定量核磁共振、高级成像后 处理工具、纵向研究设计和实施以及生物力学与临床之间的联系 关节疾病的影响因素。指导团队由物理治疗师、放射科医生、生物工程师和 是影像、临床干预和办公自动化方面的专家的整形外科医生。这项提案将提供 R01的初步数据侧重于影响不同假体类型长期结果的关键因素。

PROJECT SUMMARY The overarching objective of this proposal is to determine if transfemoral osseointegrated prostheses have a positive influence on the etiology of hip osteoarthritis (OA). The two leading causes of disability following transfemoral amputation are chronic skin pathologies due to poor socket fit (e.g., ulceration) and OA due to habitually altered joint loading. Osseointegrated prostheses are a recent clinical intervention to treat socket related pathologies by directly mounting the prosthesis to the residual limb through a bone anchored implant, providing a more normative load transmission from the ground to residual limb. This proposal will determine if this improved load transmission has positive role on the pathogenesis of hip OA differently than socket prostheses. This will be accomplished through a longitudinal study design that will compare the most common biomechanical etiological factors to OA progression at two timepoints (baseline and 12-months) between two groups (patients with osseointegrated prostheses and patients who successfully use a traditional socket prosthesis). In Aim 1, we will quantify bilateral hip muscle quality using fat fraction quantitative magnetic resonance imaging (MRI). Using these images, we will quantify 3D muscle volume and levels of fatty infiltration on the bilateral hip musculature. This will elucidate if the known atrophy and poor composition due to disuse in a socket prosthesis, both of which are known to progress OA, can be reversed following prosthesis osseointegration. In Aim 2, we will quantify dynamic cartilage loading mechanics using motion capture and a subject-specific musculoskeletal contact model. Because altered cartilage loading is a primary instigator and factor in OA onset and progression, these results will determine if cartilage mechanics are normalized during activities of daily living following osseointegration. Although muscle composition and cartilage mechanics are etiological factors to OA development, we seek to assess the role of osseointegration on the clinical progression of OA. Thus, in Aim 3, we will quantify cartilage health using T2 quantitative MRI, which is currently the most sensitive methodology to assess early osteoarthritic changes in-vivo. Ultimately, we seek to use our multi-domain approach to better inform targeted interventions aimed at improving outcomes following osseointegration. The candidate’s overarching career goal is to utilize engineering-based tools to better elucidate the mechanisms to secondary pain conditions that can be used to improve targeted interventions. This proposal builds on the candidate’s current expertise by providing new training in quantitative MRI, advanced imaging post- processing tools, longitudinal research design and implementation, and links between biomechanics and clinical factors of joint disease. The mentoring team consists of physical therapists, radiologists, bioengineers, and orthopaedic surgeons who are experts in imaging, clinical interventions, and OA. This proposal will provide preliminary data for an R01 focused on key factors that affect long-term outcomes with varying prosthesis types.