Intraoperative Bone Marrow Aspirate Concentrate Injections: Evaluating Outcomes in a Randomized Controlled Trial

Background and Significance Hip pain and dysfunction are common ailments in the adult population that deleteriously impact sport participation, recreational hobbies, activities of daily living, and often the ability to earn a living. Femoroacetabular impingement (FAI) with labral tearing is a leading cause of pre-arthritic hip pain that is often treated with hip arthroscopy and labral repair. There have been significant advances in techniques utilized to treat the labrum, including segmental and circumferential reconstruction, as well as the hip capsule, including repair, plication, and reconstruction. These modern techniques have resulted in durable therapeutic gain with largely successful outcomes 10 years postoperatively. Despite these advances, severe cartilage injury diagnosed intraoperatively is associated with inferior outcomes and higher rates of short- and long-term conversion to total hip arthroplasty. Further, treatment options for acetabular and femoral head chondral damage are limited, with microfracture serving as the current standard of care.

Innovations in regenerative medicine including platelet-rich-plasma (PRP), as well as cell-based therapies including bone marrow aspirate concentrate (BMAC) have received increasing attention in both the academic and general populations. While isolated intraoperative PRP application has not shown significant benefit, multiple studies have shown promising outcomes following intraoperative e application of BMAC during hip arthroscopy for FAI. A 2021 report by Martin and colleagues found significantly improved two-year postoperative outcomes in patients with Outerbridge grade II/III acetabular chondral defects that received intraoperative BMAC compared to a matched historical control group. These findings have been reinforced by subsequent studies demonstrating superiority of BMAC compared to microfracture as well as similar patient reported outcomes in patients with Tonnis radiographic grade I-II osteoarthritis who received BMAC when compared to a non-arthritic cohort. Taken together, these recent findings suggest that intraoperative BMAC application can improve outcomes following hip arthroscopy for FAI, particularly in the setting of cartilage damage and early arthritis. To date, no level one study has evaluated the impact of intraoperative BMAC on patient outcomes following hip arthroscopy for FAI. Given the absence of available high quality literature, a blinded, randomized controlled trial Given the cost, as well as potential bias associated with BMAC application a blinded

Design & Methods Study Design The proposed study has received institutional review board approval and is currently in the registration process for randomized controlled trials at clinicaltrials.gov. The study will consist of subjects undergoing hip arthroscopy for femoroacetabular impingement that will be randomized to receive a single intraoperative BMAC/PRP injection. BMAC will be harvested through the standard arthroscopic portals adopting the methodology reported by Martin et al. allowing for patient blinding to treatment. The surgeon will not be blinded to treatment administered at the time of the procedure, however data analysis will be performed by institutional staff blinded to subject treatment arms. The study goals and methodology will be discussed with potential candidates and informed consent will be obtained in the office during the preoperative appointment. Covariate adaptive randomization will occur prior to surgery with the goal of minimizing preoperative demographic and radiographic differences between the BMAC and control group. An a priori power analysis was constructed using the international hip outcome tool (iHOT-12) minimum clinically important difference (MCID) of 13 points, a score standard deviation of 18, and an α error of 0.05, which determined 32 subjects in each group would be required to achieve sufficient power (1-β) of 80%. To allow for a 20% drop out rate, the study goal is to obtain a minimum of 40 patients for each group.

Study Methodology Study inclusion criteria will consist of patients undergoing primary hip arthroscopy to treat femoroacetabular impingement. Subjects will require a clinical diagnosis of intra-articular pathology consisting of anterior hip and/or groin pain with restricted hip motion and positive impingement testing. Study inclusion also requires the radiographic hallmarks of Cam type femoroacetabular impingement with an alpha angle greater than 60 degrees on Dunn lateral views and advanced imaging with magnetic resonance imaging (MRI) or magnetic resonance arthrography (MRA) confirming chondrolabral pathology. Subjects will be excluded if they have had prior hip arthroscopy or hip surgery, Tonnis grade II or higher radiographic osteoarthritis, congenital hip deformities including Legg-Calve-Perthes or Slipped Capital Femoral Epiphysis, rheumatologic conditions, or workers compensation claims. Patients undergoing additional arthroscopic procedures such as trochanteric bursectomy or gluteus medius repair will also be excluded.

Potential subjects will then be introduced to the study by the treating surgeon, and if interested will discuss the study further with institutional staff. Subjects will be educated on the intraoperative harvest and application of BMAC as well as potential risks and benefits of the procedure. Given that the patient is under general anesthesia for the hip arthroscopy procedure, and no additional portals or incisions are created, additional risks related to harvest are considered minimal. Patients interested in participating in the study will be instructed that they will be randomized prior to their surgery and that they may or may not receive BMAC treatment depending on the results of the randomization. Patients that are not interested in participating in the study will still be offered intraoperative BMAC application but will be instructed that this will occur as an out-of-pocket expense. The patient will then be formally consented for the study by office staff. Randomization will be carried out according to the covariate adaptive methodology described by Frane et al to minimize potential demographic and radiographic differences between groups, with the designated treatment group sealed in an envelope to be opened at the time of surgery.