Treatment of Early-Stage Osteonecrosis of the Femoral Head
A review of literature providing insights into one of the head-sparing surgical treatments for this multifactorial disease process: core decompression with the addition of bone marrow aspirate concentrate, which has significantly improved long-term outcomes and has become a powerful tool in treating early-stage osteonecrosis of the femoral head.
Akash Shah, MD; Christopher Skeehan, MD; Ran Schwarzkopf, MD, MSc; and James Slover, MD, MSc
Osteonecrosis of the femoral head (ONFH) is a multifactorial disease process that can lead to early hip joint destruction in young patients. It typically occurs in patients ages 30 to 50 and is usually bilateral.  Early-stage ONFH includes the disease state prior to subchondral collapse of the femoral head seen on radiographs or advanced imaging, while late-stage ONFH includes flattening of the femoral head and progressive osteoarthritis due to articular collapse.
In the US, approximately 20,000 to 30,000 cases are diagnosed each year, accounting for 5% to 12% of annual total hip arthroplasties (THA).  Left untreated, the femoral head undergoes articular cartilage collapse and leads to early hip osteoarthritis in 80% of symptomatic and 66% of asymptomatic patients. 
The blood supply of the femoral head is an important determining factor in understanding the pathogenesis of ONFH. From birth to age 4, individuals have a dual blood supply from the medial and lateral femoral circumflex arteries and the ligamentum teres. At ages 4 to 20, their blood supply shifts to the medial femoral circumflex artery. Finally, the blood supply is provided by the medial femoral circumflex artery and lateral epiphyseal arteries in individuals older than age 20. Disruption of the blood supply provided by the medial femoral circumflex artery and lateral epiphyseal arteries leads to sequelae of ONFH.
Several risk factors are associated with ONFH:
- Corticosteroid use
- Excessive alcohol intake
- Coagulation disorders
- Autoimmune diseases
- Storage disease
The exact pathogenesis of ONFH is unknown but is thought to be multifactorial and to include a combination of vascular interruption, thrombotic occlusion, and extravascular compression that can decrease blood flow and cause ischemia and necrosis. Patients who are typically affected have several comorbidities that preclude normal bone repair processes, as well as decreased mesenchymal stem cell differentiation. This ultimately leads to an inability to adequately restore normal structural integrity of the bone and prevent subsequent femoral head collapse.
Presentation of ONFH can be variable, and patients may be asymptomatic with normal radiographs. If the index of suspicion for ONFH is high, the surgeon should order magnetic resonance imaging (MRI) to assess for bone edema in the proximal femur. More commonly, patients present with progressive groin pain and decreased internal rotation of the hip. It is important to assess the contralateral hip, as the disease can be bilateral.
Multiple staging systems can be used to classify ONFH:
- The Ficat and Arlet staging system is based on radiographic parameters. It emphasizes the crescent sign, which is radiographic evidence of cartilage delamination from underlying bone.
- The Steinberg University of Pennsylvania staging system incorporates MRI findings and percent of femoral head involvement. It also uses the crescent sign in staging ONFH.
- The modified Kerboul Method provides quantitative data for assessing the risk of femoral head collapse. It is based on measuring the maximum necrotic angle on coronal and sagittal MRI cuts: less than 190° is low risk, between 190° and 240° is moderate risk, and more than 240° is high risk. 
The goals of surgical management of ONFH include creating a painless hip joint, maintaining femoral head sphericity, and delaying the need for THA. Procedures indicated to treat ONFH can be divided into head-sparing and arthroplasty options:
- Head-sparing procedures are most appropriate for patients with a hip in a pre-collapse stage with a small lesion. Younger, more active patients with a hip in a pre-collapse stage but with a large lesion may also be candidates.
- Arthroplasty is more appropriate for older, more sedentary patients with a hip in a pre-collapse stage with a large lesion. It is also the best option for patients whose hips are in a post-collapse stage.
Head-sparing surgical treatment options include core decompression with or without the addition of bone marrow aspirate concentrate (BMAC) and vascularized fibular autograft. This article will focus on core decompression and BMAC. Core decompression is thought to reduce intraosseous pressure and stimulate stem cell regeneration. As a result, outcomes depend on bone remodeling and reconstruction of the necrotic area.
Outcomes were found to be improved with the addition of the bone marrow stem cells in a randomized controlled trial comparing core decompression alone with core decompression plus BMAC in patients with early-stage ONFH.  These patients typically have multiple medical comorbidities that can affect their remodeling potential after injury. The study authors proposed that core decompression with BMAC gives a higher potential for symptom resolution. In addition, the core decompression with BMAC group had greater improvement in patient-reported outcomes, based on VAS and WOMAC scores, in the study’s 2-year follow-up period. 
Changes on MRI were also significant between groups. Improvement in symptoms and MRI findings occurred in 3 of 28 patients in the core decompression with BMAC group, while worsening symptoms and MRI findings were seen in 10 patients in the core decompression alone group. Three patients in the latter group went on to conversion to THA.  The limitations of this randomized controlled trial include the small study population and short follow-up period.
Optimal outcomes with BMAC use depend on the properties of the stem cells collected and host factors. In the sentinel paper by Hernigou and Beaujean,  hips with Ficat stages I or II had a 6% conversion rate to THA, while Ficat stages III and IV hips had a 57% conversion rate. The authors said that the optimal amount of stem cells injected is 2 million/mL. Moreover, the etiology of ONFH played a significant role in the amount of stem cells able to be concentrated. Patients with a history of steroid use, excessive alcohol intake, or organ transplantation had the lowest concentration of stem cells. 
Mid-term results of core decompression with BMAC are similar to short-term outcomes. In a retrospective study by Gangji et al,  5-year progression to Ficat stage III occurred in 73% of hips treated with core decompression alone compared with 23% of hips treatment with core decompression and BMAC. The authors concluded that BMAC can significantly improve pathology in Ficat I and II hips and delay the need for arthroplasty. 
The exact mechanism and duration of action of concentrated stem cells has also been evaluated. In a proof-of-concept study, Theruvath et al  injected iron tracer molecules into patients 1 or 2 days prior to their core decompression procedure. Cells in normal bone marrow take up the tracer, leading to dark signal on MRI. During the decompression procedure, the marrow cells were harvested from the iliac crest, spun down, and injected into the necrotic segment of the femoral head. Patients were then followed by serial MRIs. One week after core decompression, the authors noted hypo-intense signals in the decompression track and in the edematous femoral head. In addition, at 1- and 6-month follow-up, the hypo-intense signal and area of femoral head edema decreased without collapse of the femoral head. 
Studies examining long-term results of core decompression with BMAC are also promising. Thirty-year follow-up of patients with bilateral disease treated with either core decompression alone or core decompression with BMAC show a clear divide in outcomes. At the end of the study period, 76% of core decompression hips progressed to arthroplasty, while only 24% of core decompression with BMAC hips progressed to arthroplasty.  The authors also noted that the mean volume of repair was 16.4cm3, with affected femoral head volume decreasing from 44.8% to 12%. 
Early THA for osteonecrosis can pose significant challenges to patients in the long term. In a case control study, Hart et al  compared outcomes of early THA for ONFH with outcomes of primary THA for osteoarthritis. The 15-year reoperation rate was 10.5% for the osteonecrosis group compared with 6.4% for the osteoarthritis group. The most common causes of revision were periprosthetic joint infection (36%) and instability (24%). The specific etiology of ONFH can be a significant factor in long-term outcomes, with steroid use and idiopathic resulting in the worst outcomes: 12.1% and 25% complication rates, respectively, in the study by Hart et al. 
Osteonecrosis of the femoral head is a multifactorial disease process that can cause serious long-term consequences in relatively young patients. Observing patients with protected weight-bearing can lead to a high rate of femoral head collapse. The addition of BMAC to core decompression has significantly improved long-term outcomes and has become a powerful tool in treating early-stage ONFH. Relative indications for core decompression with BMAC include pre-collapse lesions in younger and more active patients. Early THA for ONFH can provide a predictable outcome but can be associated with high long-term complication rates, about which patients must be counseled.
Akash Shah, MD, and Christopher Skeehan, MD, are NYU/ISK Adult Reconstruction Fellows at NYU Langone Health, New York, New York. Ran Schwarzkopf, MD, MSc, and James Slover, MD, MS, are from the Division of Orthopedics, Adult Joint Reconstruction, at NYU Langone Health, New York, New York.
Disclosures: The authors have no disclosures related to this article.
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