Oral Corticosteroids and Osteonecrosis Risk
The 2024 nationwide nested case-control study by the National Health Insurance Service found that oral corticosteroids significantly increase the risk of osteonecrosis with an odds ratio of 13.23 (95% CI: 3.34-52.33, p<.001) 1.
Risk Factors and Mechanism
Oral corticosteroids are strongly associated with osteonecrosis through several mechanisms:
- Corticosteroids decrease bone formation and increase bone resorption through effects on calcium regulation and inhibition of osteoblast function 2
- They can lead to fat cell hypertrophy causing increased intraosseous pressure 3
- Three proposed mechanisms include: vascular interruption, vascular occlusion, or extravascular intraosseous compression 3
Dose-Response Relationship
The risk of osteonecrosis is clearly dose-dependent:
- The risk increases rapidly when cumulative prednisolone use reaches ≥1,800 mg 1
- High-dose glucocorticoids combined with azathioprine resulted in significantly more cases of avascular necrosis than low-dose combinations (odds ratio 2.74,95% CI: 1.69-4.44, p<0.001) 3
- Low-dose glucocorticoids (average <7.5 mg prednisolone daily, maximum <30 mg daily) were not associated with increased osteonecrosis risk in adults 4
- Even short-term, low-dose oral corticosteroids (methylprednisolone taper packs) increase relative risk of osteonecrosis by 1.591 after a single pack and 2.763 after multiple packs 5
Age-Related Differences
The risk of corticosteroid-induced osteonecrosis varies significantly by age:
- Adults show clear dose-related association with osteonecrosis 4
- Young adults (ages 18-49) have higher risk (aHR 2.1,90% CI 1.5-2.9) compared to older adults (ages ≥50, aHR 1.3,90% CI 1.01-1.7) 4
- Children show no detectable increased risk of osteonecrosis with glucocorticoid exposure 4
- Dexamethasone showed improved outcomes during induction in patients younger than 10 years but was associated with higher risk of osteonecrosis in patients 10 years or older 3
Anatomical Distribution
Osteonecrosis commonly affects:
- Femoral head (most common site) 3
- Humeral head 3
- Tibial metadiaphysis 3
- Femoral metadiaphysis 3
- Scaphoid, lunate, and talus 3
In nontraumatic cases, femoral head osteonecrosis is often bilateral (70%-80%) 3.
Clinical Implications
When prescribing corticosteroids:
- Use the lowest possible dose for the shortest duration 2
- Consider calcium and vitamin D supplementation, bisphosphonates, and weight-bearing exercise for patients requiring prednisone equivalent of ≥5 mg for ≥3 months 2
- Monitor for early symptoms of osteonecrosis, particularly hip or joint pain 6
- Consider MRI for early detection, as it is the most sensitive imaging modality for osteonecrosis 3, 6
- Be particularly cautious in patients with additional risk factors: alcohol use, HIV, lymphoma/leukemia, blood dyscrasias, chemotherapy, radiation therapy 3
Conclusion
The evidence strongly supports a causal relationship between oral corticosteroids and osteonecrosis, with higher doses posing greater risk, particularly in adults. Clinicians should use the lowest effective dose for the shortest duration possible and consider preventive measures for bone health when longer-term therapy is required.