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.
