How long should Xgeva (denosumab) be held before a dental procedure?

Timing of Xgeva (Denosumab) Discontinuation Before Dental Procedures

For patients receiving Xgeva (denosumab), there is insufficient evidence to support routine discontinuation before dental procedures, but when discontinuation is deemed necessary for high-risk procedures, it should be held for at least 6-8 weeks prior to the procedure.

Risk Assessment and Recommendations

For Low-Risk Dental Procedures:

• No discontinuation necessary for routine dental cleanings, fillings, or other non-invasive procedures
• Maintain good oral hygiene and follow routine dental care during Xgeva therapy

For High-Risk Dental Procedures:

• Consider holding Xgeva for 6-8 weeks before invasive dental procedures when clinically feasible
• High-risk procedures include:
  • Tooth extractions
  • Dental implant placement
  • Periodontal surgery
  • Other procedures involving bone manipulation

Rationale and Evidence Base

Denosumab (Xgeva) is associated with medication-related osteonecrosis of the jaw (MRONJ), particularly at oncologic doses. The risk is significantly higher than with oral bisphosphonates:

• Denosumab for osteoporosis: 2.3% risk of MRONJ after dental extractions 1
• Oral bisphosphonates: 0.1-0.3% risk 1

The MASCC/ISOO/ASCO clinical practice guideline states: "For patients with cancer who are receiving a BMA at an oncologic dose, there is insufficient evidence to support or refute the need for discontinuation of the BMA before dentoalveolar surgery" 2.

Risk Factors for MRONJ

Several factors increase the risk of developing MRONJ after dental procedures:

• Pre-existing inflammation (OR 243.77)
• Corticosteroid therapy (OR 73.50)
• Periapical periodontitis (OR 14.13)
• Longer duration of denosumab therapy (OR 4.69)
• Female sex (OR 1.04) 3
• Multiple extractions (OR 1.35 per additional extraction) 1

Preventive Measures

Before initiating Xgeva therapy:

• Complete comprehensive dental assessment
• Perform necessary invasive dental procedures
• Develop a dental care plan coordinated between dentist and oncologist 2

During Xgeva therapy:

• Maintain excellent oral hygiene
• Schedule regular dental follow-ups every 6 months
• Address modifiable risk factors (ill-fitting dentures, uncontrolled diabetes, tobacco use) 2

Post-Procedure Management

If dental surgery is performed:

• Schedule follow-up evaluations every 6-8 weeks until complete mucosal coverage of the surgical site 2
• Maintain communication between dental specialist and oncologist regarding healing status
• Consider delaying resumption of Xgeva until adequate healing has occurred

Important Caveats

1. Drug holiday timing: A study found that patients who had extractions between 6-7 months after the last denosumab injection (just before the next scheduled dose) had no cases of MRONJ 1, suggesting this might be an optimal window for necessary dental procedures.

2. Rebound effect: Be aware that discontinuing denosumab can lead to rapid bone mineral loss and increased fracture risk due to rebound bone turnover 4. This risk must be balanced against the risk of MRONJ.

3. Individualized approach: The decision to discontinue Xgeva should involve discussion between the oncologist, dental specialist, and patient, weighing the risk of MRONJ against the risk of disease progression or skeletal-related events.

4. Limited evidence: Current recommendations are based on limited evidence, as there are no randomized controlled trials specifically addressing the optimal timing of denosumab discontinuation before dental procedures.