Effect Of Antiplatelet Therapy On The Progression Of Osteonecrosis Of The Femoral Head: A Retrospective Analysis
Authors: Routy Bertrand , Albers Anthony , Carli Alberto , Harvey Edward , Séguin Chantal 
Published: October 2019

Introduction
Nontraumatic osteonecrosis (ON) of the femoral head, previously referred to as avascular or aseptic necrosis, is a progressive disease of young adults that produces significant morbidity and often leads to early requirement for total hip arthroplasty. Nontraumatic ON is attributed to multiple etiologies, with the most prevalent including corticosteroid use, alcohol abuse and sickle cell disease. Some authors have demonstrated an association with genetic mutations involving the coagulation cascade, while others currently believe that nontraumatic ON occurs in part due to fatty emboli and intravascular coagulation secondary to endothelial dysfunction. Therefore interest is emerging in developing medical therapies which target endothelial-coagulation interactions. Treatment regimens including bisphosphonates, non-steroidal anti-inflammatories and modified weight bearing have not been shown to prevent or halt disease progression. Low molecular weight heparin (LMWH) has been shown to delay progression of early ON, but concerns exist regarding side effects, especially bleeding, and lack of long term follow up. Oral treatment with acetylsalicylic acid (ASA) is an appealing alternative to LMWH. Achieving anticoagulation through its anti-platelet effect, ASA also modulates the vascular endothelium via lipoxin A4, a lipid mediator involved in inflammation. ASA is also an mTor inhibitor and may have a favorable metabolic effect in this context. Therefore, we conducted a retrospective study to assess the effect of ASA in preventing nontraumatic ON progression.

Methods
A retrospective chart review of patients attending the ON clinic at McGill University Health Centre was performed. Patients were included for review if 1) they had an established diagnosis of pre-collapse (Ficat or Steinberg stages I or II) ON of one or both hips and 2) were prescribed ASA 81mg daily following their diagnosis. Exclusion criteria included: traumatic ON, previous hip surgery, previous use of anticoagulants and/or biphosphonates, and failure to comply with treatment. Patient characteristics recorded for analysis included age, gender, medical factors for ON, hip radiographs and magnetic resonance imaging (MRI) both at diagnosis and at most recent follow-up, and need for surgical intervention. To objectively quantify disease stage and percentage of femoral head involvement, blinded musculoskeletal radiologist assessed radiographs and MRIs. Patients were compared to established historic controlsof nontraumatic ON which have been previously validated in the literature (Stulberg BN et al. 1991 and Koo KH et al.1995). Radiographic evidence of ON progression was compared using a Fisher’s exact test with p = 0.05.

Results
12 hips in 10 patients (six males, four females) met study criteria and were included for analysis. Average patient age was 52.9+15 years with an average follow-up of 3.7 years. Two hips were diagnosed as primary osteonecrosis and 10 were secondary. The most frequent risk factors in patients were: prior use of corticosteroids (5/10), sickle cell disease (4/10) and elevated alcohol consumption (1/10). All patients had Ficat stage II disease at diagnosis with an average area of femoral head involvement of 42.5%. ASA did not cause any adverse effects in this series nor was it discontinued for any reason. Progression in those taking ASA compared favorably: 1/12 (8%) progression vs. 63% progression of historic controls with a minimum two-year follow-up (p = 0.002).

Discussion
This retrospective study evaluated the use of ASA for treatment of patients with pre-collapse stage ON of the hip. In comparison to historical controls, those treated with ASA had a significantly lower rate of progression over an intermediate follow-up period, with only one patient requiring total hip arthroplasty. There were no documented adverse events related to treatment. Accordingly, ASA may be a simple yet effective treatment option to halt disease progression. We hypothesize that ASA stalls ON via its antiplatelet activity and its modulatory effect on endothelium via lipoxin A4 and its metabolic effect via mTor inhibition. Although the current study includes a small sample size, it is comparable to current literature examining novel medical applications in ON and is the basis for a larger, prospective study examining the potential benefit of ASA, which is already underway.

Disclosures:
Off Label Use: Utilization of acetylsalicylic acid (aspirin) to prevent progression of nontraumatic osteonecrosis of the femoral head.