What are the risk factors for Avascular Necrosis (AVN)?

Risk Factors for Avascular Necrosis

Corticosteroid therapy is the leading iatrogenic risk factor for AVN, particularly with high-dose and prolonged treatment, while chronic alcohol abuse and sickle cell disease represent the most common non-iatrogenic systemic causes. 1, 2

Major Risk Factors

Corticosteroid Therapy

• High-dose and prolonged corticosteroid treatment is the most important modifiable risk factor, with risk increasing proportionally to cumulative dose and duration 3, 1, 2
• In kidney transplant patients, high-dose glucocorticoids resulted in at least 1.5-fold greater risk of AVN compared to low-dose regimens 3, 2
• The mechanism involves lipid hypertrophy causing extravascular intraosseous compression and elevated marrow pressure 2
• Cyclosporine may reduce AVN incidence by permitting lower steroid doses, though this evidence comes from studies with historical controls 3

Alcohol Abuse

• Chronic alcohol consumption is a major independent risk factor for bilateral AVN 1, 2, 4
• Alcohol-related AVN typically affects younger patients and is frequently bilateral 5, 6

Hemoglobinopathies

• Sickle cell disease is particularly important, especially in younger patients 1, 2, 4
• Blood dyscrasias including lymphoma and leukemia predispose to bilateral AVN 3, 2

Secondary Systemic Risk Factors

HIV and Antiretroviral Therapy

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

Metabolic and Hematologic Conditions

• Hyperlipidemia contributes through fat emboli formation 1, 2, 4
• Hypercoagulability states cause microvascular thrombosis 1, 2, 4
• Gaucher disease causes bilateral AVN through marrow infiltration and vascular compromise 3, 2

Treatment-Related Factors

• Chemotherapy damages vascular endothelium 3, 2
• Radiation therapy causes radiation-associated arteritis affecting vessels of any size 3, 2
• Longer duration of dialysis prior to kidney transplantation increases AVN risk post-transplant 3, 2

Occupational and Environmental

• Caisson disease produces nitrogen bubble emboli in divers and compressed air workers 3, 2

Trauma

• Trauma causes local AVN through direct vascular interruption, typically resulting in unilateral disease 3, 7
• This contrasts with nontraumatic AVN, which is bilateral in 70-80% of cases 2

Clinical Pitfall

Many patients with bilateral AVN are asymptomatic in early stages, with positive MRI findings in approximately 5% of at-risk patients, making screening of high-risk populations critical 1, 2, 4