Risk Factors for Avascular Necrosis
The most important risk factors for AVN are corticosteroid therapy, chronic alcohol abuse, trauma, sickle cell disease, and HIV infection, with corticosteroids being the leading iatrogenic cause. 1, 2
Major Risk Factors
Corticosteroid Therapy
- High-dose and prolonged corticosteroid treatment is the leading iatrogenic cause of AVN, particularly affecting adults in their third to fifth decades of life 1, 2
- The mechanism involves lipid hypertrophy causing extravascular intraosseous compression and elevated marrow pressure 2, 3
- Risk increases with cumulative dose and duration of therapy 2, 3
- In kidney transplant patients, high-dose glucocorticoids resulted in at least 1.5-fold greater risk of AVN compared to low-dose regimens 1
Alcohol Abuse
- Chronic alcohol consumption is a major independent risk factor for bilateral AVN 2, 4, 3
- Alcohol abuse significantly increases risk through mechanisms similar to corticosteroid-induced AVN 1, 2
Trauma
- Trauma is a well-established risk factor, particularly for femoral neck fractures, hip dislocations, proximal humerus fractures, talar neck fractures, and scaphoid fractures 1, 5
- Displaced femoral neck fractures carry higher risk than undisplaced fractures 6, 5
- Traumatic AVN is typically unilateral, distinguishing it from systemic causes which are bilateral in 70-80% of cases 3
Hematologic and Systemic Conditions
Blood Disorders
- Sickle cell disease is a particularly important cause, especially in younger patients 2, 3, 7
- Vaso-occlusion secondary to sickling leads to osteonecrosis, commonly affecting the femoral and humeral heads 7
- Other blood dyscrasias including lymphoma and leukemia predispose to bilateral AVN 1, 3
HIV and Antiretroviral Therapy
- HIV infection itself increases AVN risk independent of treatment 4, 3
- Approximately 5% of HIV patients have asymptomatic bilateral AVN detectable on MRI 2, 3
- The combination of HIV plus corticosteroids creates synergistic risk 3
Metabolic and Vascular Risk Factors
Lipid and Coagulation Disorders
- Hyperlipidemia contributes through fat emboli formation and is an established risk factor 2, 4, 3
- Hypercoagulability states cause microvascular thrombosis leading to AVN 2, 4, 3
Other Systemic Conditions
- Gaucher disease causes bilateral AVN through marrow infiltration and vascular compromise 1, 3
- Caisson disease produces nitrogen bubble emboli in divers and compressed air workers 1, 3
Iatrogenic Risk Factors
Cancer Treatment
- Chemotherapy damages vascular endothelium and is a recognized risk factor 1, 3
- Radiation therapy causes radiation-associated arteritis affecting vessels of any size 1, 3
Transplantation-Related Factors
- Longer duration of dialysis prior to kidney transplantation increases AVN risk post-transplant 1, 3
- Glucocorticoid dosage in transplant recipients is a critical determinant of AVN development 1
Pathophysiologic Mechanisms
Three primary mechanisms lead to AVN: vascular interruption, vascular occlusion, and extravascular intraosseous compression 1, 3
- Vascular interruption occurs through direct vessel injury from trauma 3
- Vascular occlusion results from microscopic fat emboli, sickle cells, nitrogen bubbles, or focal clotting due to procoagulant abnormalities 8
- Extravascular intraosseous compression occurs through elevated marrow pressure from lipid hypertrophy, particularly with corticosteroid use 2, 3, 8
Critical Clinical Pitfall
Many patients with bilateral AVN are asymptomatic in early stages, with positive MRI findings in approximately 5% of at-risk patients 2, 4, 3. This underscores the importance of screening high-risk populations even in the absence of symptoms, as early detection allows for joint-preserving interventions before subchondral collapse occurs 2.
Multifocal Pattern Recognition
When bilateral femoral head AVN is present, other sites are frequently involved: knee (44% of cases), ankle (17% of cases), and shoulder (15% of cases) 1, 3. This pattern is particularly common in patients on long-term corticosteroid therapy 1.