How common is osteonecrosis of the jaw with Xgeva?

October 11, 2025 •

3 min read

While osteonecrosis of the jaw (ONJ) is a serious and rare side effect, studies indicate that its incidence with high-dose Xgeva (denosumab) used for cancer treatment is higher than previously thought and appears to increase with longer treatment duration. A significant risk of osteonecrosis of the jaw with Xgeva exists, especially in patients with pre-existing dental issues or those undergoing invasive dental procedures.

Quick Summary

Studies reveal that the risk of medication-related osteonecrosis of the jaw is a known side effect of Xgeva, with incidence rates increasing with treatment duration and higher dosages. Key risk factors include invasive dental procedures and poor oral hygiene, highlighting the importance of preventative dental care before and during therapy.

Key Points

Increasing Incidence with Duration: The risk of osteonecrosis of the jaw with Xgeva is directly linked to the duration of treatment, with higher cumulative incidence rates observed over time in cancer patients.
Dosage Matters: The high doses of Xgeva (120 mg) used for cancer treatment carry a significantly higher risk of ONJ than the lower doses (60 mg) used for osteoporosis.
Invasive Dental Procedures are a Key Trigger: A history of tooth extraction or other oral surgery is a major risk factor for developing ONJ while on Xgeva.
Comparative Risk: Some studies suggest that Xgeva (denosumab) may carry a higher risk of ONJ than high-dose bisphosphonates like zoledronic acid in cancer patients, especially when switching from bisphosphonates to denosumab.
Prevention is Paramount: A thorough dental exam before starting Xgeva, combined with rigorous oral hygiene and avoidance of invasive dental procedures, is the most effective strategy to prevent ONJ.
Collaborative Care is Essential: Effective management of ONJ risk requires close collaboration between the patient's oncologist and dentist.

Understanding Osteonecrosis of the Jaw (ONJ)

Osteonecrosis of the jaw (ONJ) is a severe condition characterized by the death of bone tissue in the jaw, leading to exposed bone in the mouth that fails to heal. This can result in pain, infection, swelling, and loosening of teeth. While ONJ has been linked to various medications and conditions, a specific concern surrounds the use of potent antiresorptive agents, such as denosumab (Xgeva).

What is Xgeva (Denosumab)?

Xgeva contains denosumab, a monoclonal antibody used to prevent skeletal-related events in adults with bone metastases from solid tumors and to treat giant cell tumors of the bone. Denosumab inhibits RANKL, a protein vital for osteoclast function, which helps slow bone breakdown but can also hinder jawbone healing, potentially leading to ONJ.

Incidence of Osteonecrosis of the Jaw with Xgeva

The incidence of osteonecrosis of the jaw with Xgeva varies based on factors like the patient's condition, treatment duration, and other risks. For cancer patients receiving high-dose Xgeva (120 mg monthly), the risk is higher and increases over time. Studies have reported cumulative incidences ranging from 2.66% to over 15% with longer exposure. The majority of ONJ cases often occur in patients with existing risk factors.

Risk Factors for ONJ with Xgeva

Several factors increase the risk of ONJ while on Xgeva:

Treatment Duration and Dose: Risk increases with longer exposure and the higher cancer treatment dose.
Invasive Dental Procedures: Procedures like extractions or implants are major triggers.
Poor Oral Hygiene: Pre-existing dental issues increase infection risk.
Comorbidities: Conditions like diabetes and hypertension increase likelihood.
Concomitant Therapies: Chemotherapy, antiangiogenic agents, and corticosteroids can elevate risk.
Previous Antiresorptive Therapy: Prior bisphosphonate use increases risk due to additive effects.

Comparing ONJ Risk: Xgeva vs. Bisphosphonates

Both Xgeva and high-dose intravenous bisphosphonates are used for bone metastases, but studies on which carries a higher ONJ risk are conflicting. Some analyses suggest a statistically higher risk with denosumab, while real-world studies often show a higher risk for denosumab. Switching from bisphosphonates to denosumab significantly increases the risk.


Feature	Xgeva (Denosumab)	Zoledronic Acid (Bisphosphonate)
Mechanism of Action	Monoclonal antibody inhibiting RANKL.	Inhibits osteoclast activity by binding to bone mineral.
Route of Administration	Subcutaneous injection, typically every 4 weeks.	Intravenous infusion, typically every 3-4 weeks.
ONJ Incidence	Potentially higher incidence, increases with duration/dose.	Well-established risk, generally lower than Xgeva in some comparisons.
Elimination	More temporary bone effects, reversible on discontinuation.	Long-lasting effect due to accumulation in bone.
Risk with Prior Therapy	Significantly higher risk when switching from zoledronic acid.	Risk can be elevated with prior therapy, but switching to denosumab is a major risk factor.

Minimizing Your Risk of ONJ

Preventive measures are crucial for patients on Xgeva:

Pre-treatment Dental Assessment: Complete a thorough dental exam and any necessary procedures before starting Xgeva.
Communicate with Your Healthcare Team: Keep your dentist and oncologist informed.
Maintain Excellent Oral Hygiene: Brush, floss, and inspect your mouth daily.
Avoid Invasive Dental Procedures: Avoid elective procedures; discuss urgent needs and potential drug holidays with your team.
Address Infections Promptly: Seek immediate attention for any oral infection or non-healing issues.
Check Denture Fit: Ensure dentures fit correctly to prevent irritation.

Conclusion

Xgeva is beneficial for cancer patients, but ONJ is a serious, well-documented risk that increases with prolonged use. The risk is generally higher in cancer patients on high doses compared to those treated for osteoporosis. Risk factors include invasive dental procedures, poor oral hygiene, and concomitant drug use. Minimizing risk involves pre-treatment dental assessment, strict oral hygiene, avoiding invasive procedures, and open communication between dental and medical teams. Vigilant management is essential, and the benefits of Xgeva often outweigh the risks. For more information on ONJ prevention, consult guidelines from the National Cancer Institute.

Frequently Asked Questions

The incidence varies, but some studies have reported cumulative rates increasing over time. For example, some cohorts have shown rates of up to 7% or more annually after two years of treatment, with some long-term studies showing cumulative incidences exceeding 15%.

Yes, clinical trials and observational studies have shown that the risk of ONJ is higher with longer duration of exposure to Xgeva.

Invasive procedures like tooth extractions, dental implant placement, and other surgeries involving the jawbone are significant triggers for ONJ. It's recommended to complete any necessary procedures before starting Xgeva therapy.

To reduce your risk, have a comprehensive dental exam before starting treatment, maintain excellent daily oral hygiene, and avoid invasive dental procedures. Regular dental check-ups and prompt reporting of any oral symptoms are also crucial.

For cancer patients, studies comparing high-dose Xgeva (denosumab) to high-dose intravenous bisphosphonates like zoledronic acid have yielded mixed results, but recent real-world data suggests Xgeva may carry a somewhat higher risk. Switching from a bisphosphonate to Xgeva also appears to elevate the risk.

Symptoms can range from mild to severe and include exposed jawbone that won't heal, pain, swelling, infection of the gums, loose teeth, or a feeling of numbness or heaviness in the jaw.

Elective invasive procedures should be avoided. For urgent needs, your medical team and dentist will need to collaborate on a plan, which might involve a temporary suspension of your Xgeva dose, known as a drug holiday, to allow for healing.