What is the role of drug holidays in the prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ)?

From the Guidelines

Drug holidays are not routinely recommended for preventing medication-related osteonecrosis of the jaw (MRONJ) in most patients taking antiresorptive medications, as the benefits of discontinuation may not outweigh the risks of skeletal-related events. For patients requiring invasive dental procedures who have been on oral bisphosphonates for more than 4 years or those with additional risk factors, a 2-month drug holiday before the procedure may be considered, resuming medication after healing is complete 1. However, for patients on intravenous bisphosphonates (zoledronic acid, pamidronate) or denosumab (Prolia, Xgeva), drug holidays are generally not recommended as they may not significantly reduce MRONJ risk and could compromise treatment of the underlying condition 1.

Key Considerations

• The long half-life of bisphosphonates means that discontinuing the medication at MRONJ diagnosis is unlikely to affect MRONJ outcomes 1
• Denosumab has a shorter plasma half-life, and temporary discontinuation may enhance MRONJ resolution, but this potential benefit must be weighed against the risk of skeletal-related events 1
• Comprehensive preventive dental care before starting antiresorptive therapy, maintaining excellent oral hygiene, regular dental check-ups, and avoiding elective invasive dental procedures when possible are more effective strategies for MRONJ prevention 1

Recommendations

• Patients should receive a comprehensive dental examination and appropriate preventive dentistry before bone-modifying therapy 1
• Active oral infections should be treated, and sites that are at high risk for infection should be eliminated 1
• Patients should maintain excellent oral hygiene and avoid invasive dental procedures, if possible, while on therapy 1
• The decision to continue or discontinue bone-targeting agents in the setting of MRONJ should be individualized and dependent on a risk-benefit ratio and the severity of bone disease 1

From the FDA Drug Label

Osteonecrosis of the jaw (ONJ) has been reported. Preventive dental exams should be performed before starting zoledronic acid injection. Avoid invasive dental procedures.

The role of drug holidays in the prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ) is not directly addressed in the provided drug label. Key points:

• The label mentions the risk of ONJ and recommends preventive dental exams and avoiding invasive dental procedures.
• There is no information on the use of drug holidays to prevent MRONJ. 2

From the Research

Role of Drug Holidays in Preventing MRONJ

The use of drug holidays as a strategy to prevent Medication-Related Osteonecrosis of the Jaw (MRONJ) has been explored in various studies.

• The concept of a drug holiday involves temporarily discontinuing antiresorptive medications, such as bisphosphonates or denosumab, before dental procedures to reduce the risk of MRONJ 3, 4.
• However, the evidence on the effectiveness of drug holidays in preventing MRONJ is limited and inconclusive 5, 6.
• Some studies suggest that drug holidays may not be necessary or effective in preventing MRONJ, and that individual patient assessment is crucial 6, 7.
• A systematic review found that there is no high-level evidence to support the use of drug holidays, due to the limited number of eligible patients and variability between studies 6.
• A randomized clinical feasibility trial found that a drug holiday did not prevent the development of MRONJ after surgical tooth extraction, and that patient-reported health state declined during the drug holiday compared to drug continuation 7.

Key Findings

• The implementation of a bisphosphonate drug holiday before dental extractions may partially recover osteoclastic activity, but does not alleviate the development of MRONJ-like lesions in osteoporotic rats 5.
• A drug holiday may not be effective in reducing the risk of MRONJ in patients with cancer receiving high-dose antiresorptive medication 7.
• The decision to use a drug holiday should be made on a case-by-case basis, taking into account individual patient factors and the specific medication being used 3, 4.

Risk Factors and Prevention Strategies

• MRONJ is a severe disease that can be caused by antiresorptive medications, such as bisphosphonates and denosumab, particularly in patients with cancer or osteoporosis 3, 4.
• Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, and ill-fitting dentures 3.
• Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, maintenance of good oral hygiene, and careful dental preparation and oral hygiene instructions 3, 4.