Autologous Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Femoral Head

摘要/项目摘要 股骨头坏死（Osteonecrosis of the femoral head，ONFH）是一种以骨循环破坏为特征的疾病， 这导致了骨髓细胞的死亡。它与进行性疼痛，骨质塌陷， 以及关节退化。全世界有1 000多万人受到影响。最 患者在35岁左右的工作高峰期被诊断出来。的发病机制及治疗 这种疾病有争议。如果早期诊断，目标是保留原生髋关节。全髋关节 替换是为痛苦的终末期疾病保留的。核心减压（CD）是最常见的 在ONFH的早期阶段进行治疗，并在病变中创建钻道。然而， CD是可变的。人们越来越关注使用骨髓抽吸浓缩物（BMAC）来增加CD。 然而，研究仅限于小病例系列，不同的疾病阶段，多种风险因素，变量 手术技术或其他方面缺乏严谨性。 需要一项随机对照试验（RCT）来获得关于 BMAC联合CD治疗早期ONFH。我们的多中心临床试验（U 01）的总体目标是测试 以下假设：“接受CD的早期ONFH患者， BMAC将比单独的CD具有更好的临床和放射学结果。本RCT还将定义具体的 决定这些手术长期结果的患者特征。 Co-PI是世界知名的专家，他们是骨坏死的学术和临床领导者。一队 高度认可的临床医生，他们在治疗骨坏死方面拥有专业知识，来自12个中心， 美国被招募。为了标准化，我们将利用一个集中的放射科医生，一个中央骨 生物实验室，以及数据管理和生物统计分析中心。 我们的具体目标是： 具体目标1（SA 1）。确定CD联合自体BMAC的结局是否优于单独CD 用于治疗早期（塌陷前）阿科I期和II期ONFH。 具体目标2（SA 2）。SA 2A。确定患者骨髓穿刺液的细胞表型， 通过飞行时间质谱细胞计数法（CyTOF）评估。SA 2B.为了建立一个多变量模型， 根据综合评估，具有满意和不满意临床和/或放射学结局的患者 质谱细胞仪细胞频率和功能特征数据集。 总之，我们已与NIAMS赞助的项目团队计划了这项多中心试验（R34 AR 073505） 并组建了一个诊断和治疗ONFH的专家团队。该试验将受益于现有的 我们的研究和基础设施。我们将确定ON患者是否受益于自体BMAC， 增加CD，并研究结果改善的生物学机制。

Abstract/Project Summary Osteonecrosis of the femoral head (ONFH) is characterized by disrupted circulation within the bony compartment, leading to death of bone and marrow cells. It is associated with progressive pain, bony collapse, and joint degeneration within months to several years. Over 10 million people are afflicted worldwide. Most patients are diagnosed in their mid-30s, during their peak working years. The pathogenesis and treatment of this disease are controversial. If diagnosed early, the goal is to preserve the native hip joint. Total hip replacement is reserved for painful end-stage disease. Core decompression (CD) is the most common treatment in the early stages of ONFH and creates a drill tract into the lesion. However, the clinical outcome of CD is variable. There is increasing interest in using bone marrow aspirate concentrate (BMAC) to augment CD. Yet, studies have been limited to small case series, different disease stages, multiple risk factors, variable surgical techniques, or otherwise have lacked rigor. A randomized controlled trial (RCT) is needed to obtain a more definitive answer regarding the efficacy of BMAC with CD for early-stage ONFH. The overall goal of our multicenter clinical trial (U01) is to test the following hypotheses: “Patients who have early-stage ONFH undergoing CD augmented with autogenous BMAC will have better clinical and radiological outcomes than CD alone.” This RCT will also define specific patient characteristics that determine the long-term outcomes of these procedures. The Co-PIs are world-renowned experts, who are academic and clinical leaders in osteonecrosis. A team of highly recognized clinicians, who have expertise in the treatment of osteonecrosis from 12 centers in the United States have been recruited. For standardization, we will utilize a centralized radiologist, a central bone biology laboratory, and a center for data management and biostatistical analysis. Our specific aims are: Specific Aim 1 (SA1). To determine if CD with autogenous BMAC results in better outcomes than CD alone for the treatment of early-stage (pre-collapse) ARCO Stage I and II ONFH. Specific Aim 2 (SA2). SA 2A. To determine the cellular phenotype of the patients’ bone marrow aspirates, as assessed by Mass Cytometry by Time of Flight (CyTOF). SA 2B. To build a multivariate model classifying patients who have satisfactory and unsatisfactory clinical and/or radiological outcomes based on the combined mass cytometry cell frequency and functional feature dataset. In summary, we have planned this multicenter trial with our NIAMS-sponsored project team (R34 AR073505) and assembled a team of experts in the diagnosis and treatment of ONFH. The trial will benefit from existing studies and infrastructure by our group. We will determine if ON patients benefit from autogenous BMAC to augment CD, and investigate the biological mechanisms underlying improvements in outcome.