What medicines can cause AVN (Avascular Necrosis)?

October 8, 2025 •

4 min read

Systemic corticosteroid use is implicated in nearly one-third of all avascular necrosis (AVN) cases, making it the leading cause of non-traumatic osteonecrosis [1.3.3, 1.3.5]. Understanding what medicines can cause AVN is the first step in risk management and prevention.

Quick Summary

An in-depth look at medications linked to avascular necrosis (AVN), also known as osteonecrosis. This overview details the primary drug classes, risk factors, and mechanisms involved in this serious bone condition.

Key Points

Corticosteroids Are the #1 Cause: Use of high-dose corticosteroids like prednisone is the most common cause of non-traumatic avascular necrosis (AVN) [1.2.1].
Dose and Duration Matter: Higher doses and longer durations of steroid therapy increase the risk of AVN, but it can occur even with short-term use [1.2.3, 1.4.3].
Jaw Necrosis is a Specific Risk: Bisphosphonates (e.g., Fosamax) and denosumab (Prolia), used for osteoporosis, are linked to a rare but serious form called osteonecrosis of the jaw (ONJ) [1.2.1, 1.5.2].
Other Drugs Implicated: Certain cancer treatments, including anti-angiogenic agents and other immunomodulators, have also been associated with ONJ [1.5.1, 1.5.3].
Early Diagnosis is Crucial: MRI is the most sensitive tool for detecting early AVN, as symptoms often appear late and the condition can lead to joint collapse if untreated [1.4.2].
Prevention Focuses on Steroid Management: Minimizing steroid dosage and duration is the primary strategy for preventing medication-induced AVN [1.6.2].
Treatment Varies by Stage: Early-stage AVN may be managed conservatively or with joint-preserving surgery, while advanced cases often require total joint replacement [1.6.1, 1.6.5].

Understanding Avascular Necrosis (AVN)

Avascular necrosis (AVN), also called osteonecrosis, is a serious condition characterized by the death of bone tissue due to a lack of blood supply [1.2.1]. This interruption in blood flow can lead to tiny breaks in the bone and its eventual collapse [1.2.1]. While trauma is a common cause, many cases are non-traumatic and linked to underlying medical conditions or, significantly, the use of certain medications [1.3.5]. The incidence of steroid-induced AVN is estimated to be between 10,000 and 20,000 cases per year in the United States alone [1.3.5]. The condition most often affects the femoral head (hip), but can also occur in the knees, shoulders, and ankles [1.3.4].

The Primary Culprit: Corticosteroids

The long-term use of high-dose corticosteroids, such as prednisone, is the most common cause of non-traumatic AVN [1.2.1, 1.3.5]. These powerful anti-inflammatory drugs are used to treat a wide range of conditions, including autoimmune diseases like lupus (SLE), asthma, and inflammatory bowel disease [1.4.2, 1.4.5]. The prevalence of glucocorticoid-induced AVN can range from 3% to 38%, depending on the underlying disease and the dosage [1.3.4, 1.3.5].

How Steroids Cause AVN

The exact mechanism is not fully understood, but several theories exist:

Altered Lipid Metabolism: Experts believe corticosteroids can increase lipid (fat) levels in the blood. These fats can form deposits in blood vessels, narrowing them and reducing blood flow to the bone [1.2.1, 1.4.2].
Fat Embolism: Steroids may cause tiny fat droplets to block the small blood vessels that supply the bones [1.4.7].
Intravascular Coagulation: Some research suggests steroids can trigger a hypercoagulable state, leading to blood clots that obstruct bone circulation [1.3.1, 1.4.2].
Cellular Changes: Steroids can skew bone marrow cell differentiation towards producing fat cells (adipogenesis) instead of bone-forming cells (osteogenesis), weakening the bone's ability to repair itself [1.4.3].

There is a documented dose-dependent relationship; daily prednisone doses over 20 mg for extended periods significantly increase risk [1.4.3]. However, AVN has also been reported with short courses and even lower doses, highlighting that there may be no completely 'safe' dose [1.3.3]. High-dose intravenous 'pulse' therapy, common in treating autoimmune flares, is also a significant risk factor [1.2.3].

Other Medications Linked to AVN

While corticosteroids are the most well-known, other medications have been associated with AVN, particularly osteonecrosis of the jaw (ONJ).

Bisphosphonates and RANKL Inhibitors

These medications are commonly used to treat osteoporosis and bone metastases from cancer. Long-term use of bisphosphonates (e.g., alendronate, zoledronic acid) and denosumab (a RANK ligand inhibitor) can contribute to osteonecrosis of the jaw (ONJ), a rare but serious complication [1.2.1, 1.5.2, 1.5.5]. The risk is significantly higher for cancer patients receiving high intravenous doses compared to those taking lower oral doses for osteoporosis [1.5.2].

Chemotherapy and Immunomodulators

Several other drugs, often used in cancer treatment, have been identified as potential risk factors for ONJ. These include:

Anti-angiogenic agents: Drugs like bevacizumab and sunitinib, which work by inhibiting the formation of new blood vessels, are linked to ONJ [1.5.3].
Immunomodulators: Medications such as lenalidomide and pomalidomide, used for multiple myeloma, have shown an association [1.5.1].
Taxanes: Chemotherapy drugs like docetaxel and paclitaxel have also been identified in case reports [1.5.1].
mTOR inhibitors: Drugs like everolimus can decrease levels of vascular endothelial growth factor (VEGF) and inhibit cell growth, which may contribute to ONJ [1.5.1].

Medication Risk Comparison Table


Medication Class	Common Examples	Primary Use	Associated AVN Type	Risk Level
Corticosteroids	Prednisone, Dexamethasone, Methylprednisolone	Autoimmune diseases, Asthma, Allergies	Femoral Head, Knee, Shoulder (Systemic)	High [1.2.1, 1.3.5]
Bisphosphonates	Alendronate (Fosamax), Zoledronic acid (Reclast)	Osteoporosis, Cancer	Osteonecrosis of the Jaw (ONJ)	Low (for Osteoporosis), Higher (for Cancer) [1.5.2]
RANKL Inhibitors	Denosumab (Prolia, Xgeva)	Osteoporosis, Cancer	Osteonecrosis of the Jaw (ONJ)	Low (for Osteoporosis), Higher (for Cancer) [1.5.2]
Anti-angiogenic Agents	Bevacizumab, Sunitinib	Cancer Treatment	Osteonecrosis of the Jaw (ONJ)	Emerging evidence [1.5.1, 1.5.3]

Diagnosis, Prevention, and Treatment

Early diagnosis is critical as the disease is progressive and can lead to joint destruction within five years if untreated [1.4.2]. Symptoms often don't appear until the disease is advanced, but persistent joint pain (especially in the hip, groin, or buttock) should be investigated, particularly in patients with risk factors [1.3.5]. While X-rays can show later-stage damage, MRI is the most sensitive imaging modality for detecting early AVN [1.4.2].

Prevention

Limit Steroid Use: The most important preventive measure is the judicious use of corticosteroids—using the lowest effective dose for the shortest possible duration [1.6.2, 1.6.7].
Manage Risk Factors: Limiting alcohol consumption and keeping cholesterol levels low can help reduce the overall risk of AVN [1.6.3].
Patient Education: Patients on long-term or high-dose steroids should be educated about the risk and early symptoms of AVN [1.6.2].

Treatment

Treatment depends on the stage of the disease.

Conservative: In the very early stages, rest, anti-inflammatory medications (NSAIDs), and physical therapy may be recommended [1.6.1].
Surgical (Joint-Preserving): For pre-collapse AVN, procedures like core decompression (drilling holes into the bone to relieve pressure and encourage blood flow) or bone grafts may be performed to save the joint [1.6.1, 1.6.5].
Joint Replacement: If the bone has collapsed, total joint replacement (arthroplasty) is often the only option to relieve pain and restore function [1.6.1].

Conclusion

The link between certain medications and avascular necrosis is well-established, with corticosteroids being the most significant cause of non-traumatic AVN. While essential for treating many conditions, the risk of AVN necessitates careful management, including using the lowest effective doses and monitoring for symptoms. Other drugs, particularly those used for osteoporosis and cancer, carry a risk for ONJ. Early diagnosis through high suspicion and sensitive imaging like MRI is key to implementing joint-preserving treatments and preventing the need for total joint replacement. Patients taking high-risk medications should have open discussions with their healthcare providers about minimizing risks and recognizing the early warning signs of this debilitating condition.

For more information from an authoritative source, visit: Mayo Clinic - Avascular Necrosis

Frequently Asked Questions

The most common medicines known to cause avascular necrosis are high-dose corticosteroids, such as prednisone. They are the leading cause of non-traumatic AVN [1.2.1, 1.3.5].

Yes, while the risk is higher with long-term, high-dose use, there are reports of AVN developing even after short courses of corticosteroids or high-dose intravenous 'pulse' therapy [1.2.3, 1.3.3].

Not typically. Osteoporosis medications like bisphosphonates and denosumab are primarily associated with osteonecrosis of the jaw (ONJ), a specific type of AVN affecting the facial bones, whereas steroids more commonly affect large joints like the hip and knee [1.2.1, 1.3.4, 1.5.5].

The main prevention strategy is to use the lowest effective dose of corticosteroids for the shortest possible duration. Limiting alcohol and managing cholesterol levels can also reduce your overall risk [1.6.2, 1.6.3].

Early stages of AVN may be asymptomatic. When symptoms do appear, they often start as pain in the affected joint, such as the hip or groin, which may be mild at first and worsen over time, especially with weight-bearing activities [1.3.5].

Some studies have shown that very early AVN lesions may undergo spontaneous regression, but this is not common. Once the disease progresses, it is generally not reversible, and treatment aims to slow its progression and manage symptoms. Untreated, it often leads to joint collapse [1.2.3, 1.6.6].

A doctor will consider your medical history, including medication use, and conduct a physical exam. While an X-ray might show changes in later stages, an MRI is the most sensitive and specific imaging test for diagnosing AVN in its early stages [1.2.4, 1.6.7].