Anticoagulant Therapy for the Treatment of Idiopathic Osteonecrosis.
Authors: Shehadat Saaib Al , Bociek Gregory R. , Haire William 
Published: October 2019

Abstract
Background: Studies suggest that thrombosis may play an important etiologic role in adults with idiopathic osteonecrosis. Thrombotic occlusion in the bone leads to increased intraosseus venous pressure, reduced arterial flow, and ultimately hypoxic bone death. Total joint arthroplasty is the standard treatment for advanced osteonecrosis. The majority of untreated patients with idiopathic osteonecrosis will progress to significant degenerative disease. We report our experience in five consecutive patients who were referred to our institute and were treated with anticoagulant therapy instead of surgical intervention.
Methods: Five adult patients (median age 38 years old, range 28–49 years) were evaluated first by an orthopedic surgeon for knee or hip pain. The diagnosis of osteonecrosis was confirmed by Magnetic Resonance Image (MRI) interpreted in all cases by both a radiologist and an orthopedic surgeon. Osteonecrosis was designated as idiopathic after eliminating other known associated factors, mainly drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease). The response to treatment was measured by pain relief, bone imaging stability or improvement, and subsequent need for surgical intervention. Treatment was discontinued if the patient developed severe toxicity or disease progression requiring surgical intervention. Four patients were treated with warfarin with a target international normalized ratio (INR) of 2–3, while one patient was treated with enoxaparin (1 mg/kg twice a day). Patients were followed up every three months by both a hematologist and an orthopedic surgeon, and MRI evaluation was performed at three month intervals for one year or when symptoms worsened. After achieving pain relief and stability of lesions on MRI, patients were given the choice of discontinuing the treatment.
Results: Three out of four patients on warfarin and the patient on enoxaparin had pain improvement within three months of initiating therapy. All patients reported a reduction of pain at a median of 7.5 months (6–9 months). MRI revealed disease stability in those patients within three months, and some radiographic signs of improvement at 9 months. Complete resolution of imaging abnormalities was seen in 5 years in one patient. Patients tolerated the therapy well without any major toxicity and decided to continue the anticoagulation therapy. One patient preferred to discontinue therapy after 4.5 years, and continued to be asymptomatic 10 months later.
The fifth patient had bilateral distal femoral and proximal tibial osteonecrosis. The patient had severe degenerative joint disease involving the right knee from previous motor vehicle accident. The patient eventually underwent right knee arthroplasty for severe pain, and the microscopic examination of the bone and debridement tissue from the joint replacement procedure showed focal avascular necrosis and features of degenerative joint disease. The patient resumed the warfarin therapy postoperatively with stability of imaging abnormalities on the left side after 3.5 years of continuous therapy. Warfarin was replaced by aspirin with eighteen months of follow up, the patient continued to be asymptomatic with stable imaging abnormalities of the left leg.
Conclusion: The findings suggest that anticoagulation therapy may benefit patients with early stage of idiopathic osteonecrosis, and may delay or eliminate the need for surgical intervention. Further studies are warranted in he future to compare different anticoagulants with placebo.