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

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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.