What is the management and prevention of medication-related osteonecrosis of the jaw (ONJ) in patients on bisphosphonates (e.g. zoledronic acid or pamidronate), denosumab, or anti-angiogenic medications (e.g. bevacizumab or sunitinib)?

Management and Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ)

All patients initiating bone-modifying agents (bisphosphonates, denosumab) or anti-angiogenic medications must undergo comprehensive dental evaluation with orthopantomography before starting therapy, complete all necessary dental extractions and periodontal interventions, and maintain 6-month dental follow-up schedules throughout treatment to prevent MRONJ. 1

Definition and Diagnosis

MRONJ is diagnosed when all three criteria are present: 1, 2

• Current or previous treatment with a bone-modifying agent (BMA) or angiogenic inhibitor
• Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region persisting for longer than 8 weeks
• No history of radiation therapy to the jaws or metastatic disease to the jaws

The 8-week timeframe is critical—shorter durations may represent normal healing and should not be diagnosed as MRONJ. 2

Prevention Strategy: Before Starting Therapy

Pre-Treatment Dental Protocol

Complete the following dental interventions before initiating BMAs or anti-angiogenic drugs: 1

• Conduct complete dental examination with orthopantomography and intraoral radiographs
• Perform all necessary dental extractions
• Complete conservative dental and periodontal interventions
• Adjust prosthetics to eliminate trauma
• Educate patients about lifelong daily oral hygiene commitment
• Address modifiable risk factors: smoking cessation, diabetes control, periodontal disease treatment

Patients referred from oncology should be seen by the dentist within 2 weeks of referral. 1

High-Risk Medications

The following medications are associated with MRONJ: 1, 2, 3

• Bisphosphonates: zoledronic acid, pamidronate (1-9% incidence in cancer patients)
• Denosumab: anti-RANKL antibody
• Anti-angiogenic agents: bevacizumab, sunitinib

Sunitinib specifically requires oral examination prior to initiation and withholding for at least 3 weeks before scheduled dental surgery or invasive dental procedures. 4

Prevention Strategy: During Therapy

Ongoing Dental Surveillance

Implement the following monitoring schedule for all patients on BMAs or anti-angiogenic therapy: 1

• Dental follow-up visits every 6 months
• Complete dental examination with orthopantomography and intraoral radiographs
• Annual orthopantomography
• Evaluate oral mucosa integrity at each visit
• Reinforce oral hygiene education continuously
• Monitor and address modifiable risk factors (smoking, uncontrolled diabetes, periodontal disease, denture trauma)

Dental Procedures During Treatment

Avoid elective dentoalveolar surgery (procedures involving teeth or contiguous alveolar bone) during BMA treatment. 1

If dental surgery becomes necessary: 4

• Withhold sunitinib for at least 3 weeks prior to scheduled dental procedures
• The evidence remains uncertain whether bisphosphonates or denosumab should be discontinued before dentoalveolar surgery 1
• Coordinate closely between oncologist and dental specialist 1

A critical caveat: Non-surgical periodontal therapy can trigger MRONJ, as documented in denosumab-treated patients, so even conservative dental procedures require careful monitoring. 5

Management of Established MRONJ

Staging and Treatment Algorithm

Refer all suspected MRONJ cases to a dental specialist experienced in MRONJ management for staging and treatment. 1

Stage 1 (Exposed/necrotic bone, asymptomatic, no infection): 1, 2

• Conservative therapy
• Improve oral hygiene
• Treat active dental and periodontal disease
• Topical antibiotic mouth rinses (chlorhexidine)

Stage 2 (Exposed/necrotic bone with pain, erythema, infection): 1, 2

• All Stage 1 interventions
• Systemic antibiotics if infection suspected
• Consider surgical debridement
• 8-week follow-up schedule with dental specialist

Stage 3 (Exposed/necrotic bone with pain, infection, plus pathologic fracture, extraoral fistula, oral-antral/oral-nasal communication, or extensive osteolysis): 1, 2

• All Stage 2 interventions
• Surgical debridement and resection
• Jaw reconstruction if necessary

Medication Management During MRONJ

Consider continuation versus discontinuation of BMA therapy in patients newly diagnosed with MRONJ, balancing cancer treatment needs against MRONJ progression. 1

For sunitinib specifically, withhold treatment for development of ONJ until complete resolution, though the safety of resumption after resolution has not been established. 4

Multidisciplinary Coordination

Essential communication pathways: 1

• Oncologist provides dentist with patient's medical diagnosis and complete antiresorptive/angiogenic inhibitor profile
• Dentist sends diagnosis and treatment plan to oncologist
• Coordinate timing if oral surgery becomes necessary
• Maintain 8-week follow-up schedule between dental specialist and oncologist for active MRONJ cases

Critical Pitfalls to Avoid

Do not rely solely on radiographic signs for MRONJ diagnosis, as this overestimates disease frequency—clinical examination with exposed bone or probeable fistula is required. 2

Biopsy of suspicious lesions is generally not recommended as it may exacerbate the condition. 2

Even non-surgical periodontal procedures carry MRONJ risk in patients on antiresorptive therapy, requiring vigilant post-procedure monitoring. 5

Pamidronate specifically requires dental examination with appropriate preventive dentistry prior to treatment, and patients should avoid invasive dental procedures while on therapy. 6