What is the relationship between prednisone (corticosteroid) and avascular necrosis (osteonecrosis)?

From the Guidelines

Prednisone use is associated with an increased risk of avascular necrosis (AVN), particularly at high doses or with prolonged treatment duration, and patients should be monitored closely for early symptoms of AVN. The risk of developing AVN is significantly higher with high-dose glucocorticoids, as shown in a meta-analysis of 5 studies that compared high-dose versus low-dose glucocorticoids, with an odds ratio of 2.74 (95% CI, 1.69 to 4.44, P 0.001) 1. This increased risk is thought to be due to the proliferation of fat cells, which can lead to high intraosseous pressure and subsequent interference with perfusion of the bone 1.

Risk Factors for AVN

• High-dose prednisone (typically above 20mg daily)
• Longer treatment duration (especially beyond 3 months)
• Cumulative steroid exposure
• Other medical conditions, such as lupus or sickle cell disease
• Alcohol consumption and smoking

Prevention and Management

• Using the lowest effective dose of prednisone for the shortest duration possible
• Monitoring patients for early symptoms of AVN, such as joint pain that worsens with weight bearing or movement
• Prompt medical evaluation with imaging (X-rays, MRI) if AVN is suspected
• Considering alternative treatments, such as bisphosphonates or denosumab, to prevent osteoporosis and reduce the risk of AVN, especially in patients with high-risk factors, as recommended by the British Society of Gastroenterology consensus guidelines 1.

Key Recommendations

• Patients on long-term prednisone therapy should have regular bone mineral densitometry tests to assess their risk of osteoporosis and AVN
• High-risk patients should be considered for prolonged bisphosphonate treatment, and/or referral to a specialist clinic
• Patients should be advised to maintain a healthy lifestyle, including a balanced diet, regular exercise, and avoidance of smoking and excessive alcohol consumption, to minimize their risk of AVN.

From the FDA Drug Label

Musculoskeletal arthralgias, aseptic necrosis of femoral and humeral heads, increase risk of fracture, loss of muscle mass, muscle weakness, myalgias, osteopenia, osteoporosis (see PRECAUTIONS: Musculoskeletal), pathologic fracture of long bones, steroid myopathy, tendon rupture (particularly of the Achilles tendon), vertebral compression fractures

Avascular necrosis is a potential adverse reaction associated with prednisone, specifically aseptic necrosis of femoral and humeral heads. This suggests that prednisone may increase the risk of avascular necrosis, particularly in the femoral and humeral heads. 2

From the Research

Avascular Necrosis and Prednisone

• Avascular necrosis (AVN) is a rare entity that can be caused by various factors, including the use of corticosteroids such as prednisone 3, 4.
• The relationship between prednisone and AVN is complex, and evidence suggests that high-dose corticosteroid administration plays a role in AVN, with peak dose, daily dose, and cumulative dose all potentially contributing to the risk of AVN 4.
• Early diagnosis and treatment of AVN are crucial to prevent joint damage and preserve joint function, and screening MRI can help detect AVN at a prefracture stage 4.

Treatment of Avascular Necrosis

• Bisphosphonates have been shown to be effective in preventing disease progression, bone collapse, and the requirement for surgery in AVN of the femoral head 5, 6, 7.
• Combination therapy with oral alendronate and intravenous zolendronic acid has been found to provide a pragmatic solution for the management of AVN, particularly in non-femoral AVN and postchemotherapy AVN of the femoral head in adolescents and young adults 5, 7.
• Clinical evaluation using tools such as the Visual Analog Scale and Harris Hip Score can help assess the response to bisphosphonate therapy, and radiographs can be used to monitor radiologic collapse and evaluate the rate of progression 5, 7.

Risk Factors and Prevention

• Risk factors for AVN include repetitive systemic corticosteroid use, underlying hyperlipidemia, alcoholism, smoking, connective tissue disorders, and previous trauma to the affected area 3.
• Recognition of risk factors and educating patients remain the most effective ways of preventing AVN caused by corticosteroid use 3.
• The use of statins for patients with hyperlipidemias may be useful in decreasing the risk of AVN, but this is considered investigational 3.