What are the underlying causes of avascular necrosis?

Underlying Causes of Avascular Necrosis

Avascular necrosis (osteonecrosis) is primarily caused by inadequate vascular supply to bone, resulting from trauma, corticosteroid therapy, alcohol use, HIV infection, blood disorders, and various other conditions that compromise blood flow to bone tissue. 1

Primary Etiological Factors

Vascular Compromise Mechanisms

Avascular necrosis occurs through three possible mechanisms:

1. Vascular interruption
2. Vascular occlusion
3. Extravascular intraosseous compression (often from lipid hypertrophy) 1

Major Risk Factors

Medication-Related

• Corticosteroid therapy - One of the most significant risk factors, with dose and duration directly correlating with risk 1
  • High-dose glucocorticoids significantly increase risk compared to low-dose regimens (1.5-fold greater risk) 1
  • Particularly concerning in transplant patients and those requiring long-term steroid treatment

Substance-Related

• Alcohol abuse - Major risk factor through direct toxicity to osteoblasts and altered fat metabolism 1

Disease-Related

• HIV infection - Associated with 5% prevalence of asymptomatic avascular necrosis 1

  • May be related to both the infection itself and antiretroviral therapy
  • Hyperlipidemia from HIV treatment may indirectly contribute to osteonecrosis 1

• Blood disorders

  • Hemoglobinopathies (particularly sickle cell disease) 1, 2
  • Lymphoma/leukemia 1
  • Coagulopathies and hypercoagulable states 1

• Other systemic conditions

  • Gaucher disease 1
  • Systemic lupus erythematosus 2
  • Pancreatitis 3

Trauma-Related

• Direct trauma to affected bones 1
• Microtrauma (repetitive stress) 4
• Caisson disease (decompression sickness) - Nitrogen bubbles occlude vessels 1, 4

Radiation-Related

• Radiation therapy - Causes direct vascular damage 1

Pathophysiological Mechanisms

Vascular Obstruction

• Intraluminal obstruction - Fat emboli, sickle cells, nitrogen bubbles, or focal clotting 4
• Extraluminal compression - Elevated marrow pressure or increased marrow fat 4

Bone Death Progression

• Critical ischemia leads to bone cell death
• Detectable 1-6 months after exposure to risk factors
• Subchondral plate fracture is the turning point, leading to collapse of the necrotic segment 4
• Collapse typically occurs within the first 2 years of disease onset

Anatomical Distribution

• Femoral head - Most common site (>75% of cases) 1, 5
• Humeral head - Second most common site 1, 2
• Other sites - Knee, talus, scaphoid, lunate 1
• Can be unifocal or multifocal (suggesting systemic cause) 5

Clinical Pearls and Pitfalls

• Early detection is crucial - Radiographs may be normal in early stages; MRI is the most sensitive diagnostic tool 5, 3
• Risk of collapse depends primarily on the size and location of the necrotic segment 4
• Bilateral involvement is common (70-80%) in non-traumatic cases, suggesting systemic etiology 1
• Asymptomatic disease is common and underdiagnosed - true prevalence likely higher than reported 1
• No accepted medical therapy exists for established avascular necrosis; surgical intervention is often necessary for disabling symptoms 1

Risk Assessment and Monitoring

• For patients on long-term corticosteroids, monitor closely for early symptoms
• In HIV patients, consider the potential contribution of both the infection and antiretroviral therapy
• For patients with multiple risk factors, maintain high clinical suspicion even with minimal symptoms
• MRI should be performed for unexplained joint pain in high-risk patients, even with normal X-rays 5

Understanding these underlying causes is essential for early identification, risk factor modification, and timely intervention to prevent progression to joint destruction and the need for joint replacement.