What are the causes of bilateral avascular necrosis?

Causes of Bilateral Avascular Necrosis

Bilateral avascular necrosis occurs predominantly due to systemic risk factors rather than trauma, with corticosteroid therapy, chronic alcohol abuse, and sickle cell disease being the most common causes. 1

Key Epidemiologic Pattern

In nontraumatic cases, femoral head osteonecrosis is bilateral in 70-80% of patients, distinguishing it from traumatic AVN which is typically unilateral. 1 This bilateral presentation is a hallmark feature that should prompt investigation for systemic causes rather than local injury.

Primary Systemic Causes

Corticosteroid Therapy

• High-dose and prolonged corticosteroid treatment is the leading iatrogenic cause of bilateral AVN. 2
• The mechanism involves lipid hypertrophy causing extravascular intraosseous compression and elevated marrow pressure. 1
• Risk increases with cumulative dose and duration of therapy. 1, 3
• In kidney transplant patients, high-dose glucocorticoids resulted in at least 1.5-fold greater risk compared to low-dose regimens. 1

Alcohol Abuse

• Chronic alcohol consumption is a major independent risk factor for bilateral AVN. 1, 4, 2
• The pathophysiology likely involves fat emboli and increased marrow fat content leading to vascular occlusion. 5

Hemoglobinopathies

• Sickle cell disease is a particularly important cause, especially in younger patients. 4, 2, 6
• Intraluminal obliteration occurs from sickled red blood cells blocking small vessels. 5

HIV Infection and Antiretroviral Therapy

• HIV infection itself increases AVN risk independent of treatment. 4, 2
• Approximately 5% of HIV patients have asymptomatic bilateral AVN detectable on MRI. 2, 3
• The combination of HIV plus corticosteroids creates synergistic risk. 3

Secondary Systemic Causes

Hematologic and Metabolic Disorders

• Blood dyscrasias including lymphoma and leukemia predispose to bilateral AVN. 1
• Hyperlipidemia contributes through fat emboli formation. 4
• Hypercoagulability states (protein C/S deficiency, factor V Leiden, antiphrombin III deficiency, lupus anticoagulant) cause microvascular thrombosis. 4, 5

Other Medical Conditions

• Gaucher disease causes bilateral AVN through marrow infiltration and vascular compromise. 1
• Caisson disease (decompression sickness) produces nitrogen bubble emboli. 1, 5
• Systemic lupus erythematosus increases risk through both disease activity and corticosteroid treatment. 6

Iatrogenic Causes

• Chemotherapy damages vascular endothelium. 1
• Radiation therapy causes radiation-associated arteritis affecting vessels of any size. 1
• Longer duration of dialysis prior to kidney transplantation increases AVN risk post-transplant. 1

Pathophysiologic Mechanisms

Three primary mechanisms lead to bilateral AVN: 1, 2

1. Vascular interruption - direct vessel injury
2. Vascular occlusion - intraluminal blockage by fat emboli, sickle cells, nitrogen bubbles, or microthrombi 5
3. Extravascular intraosseous compression - elevated marrow pressure from lipid hypertrophy 1

Critical Clinical Pitfall

Many patients with bilateral AVN are asymptomatic in early stages, with positive MRI findings in approximately 5% of at-risk patients. 4, 2 This means screening MRI should be considered in high-risk populations (chronic corticosteroid users, HIV patients, sickle cell disease) even without symptoms, as early detection allows for joint-preserving interventions before collapse occurs.

Multifocal Pattern

When bilateral femoral head AVN is present, other sites are frequently involved: 1

• Knee (44% of cases)
• Ankle (17% of cases)
• Shoulder (15% of cases)

This multifocal pattern reinforces the systemic nature of the disease process in bilateral cases.