Management and Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ)
All patients starting bisphosphonates (zoledronic acid, pamidronate), denosumab, or anti-angiogenic medications (bevacizumab, sunitinib) must undergo comprehensive dental evaluation with orthopantomography and complete all necessary dental extractions before initiating therapy, followed by 6-month dental monitoring throughout treatment. 1
Definition and Diagnostic Criteria
MRONJ is diagnosed when all three criteria are present: 1, 2
- Current or previous treatment with a bone-modifying agent 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. 1, 2
Risk Stratification by Medication and Patient Population
High-Risk Medications
- Bisphosphonates: Zoledronic acid and pamidronate carry MRONJ risk of 1-9% in cancer patients 2, 3
- Denosumab: Similar risk profile to bisphosphonates for MRONJ development 2, 3
- Anti-angiogenic agents: Sunitinib and bevacizumab increase ONJ risk, particularly when combined with bisphosphonates 4, 3, 5
Risk Factors
Modifiable risk factors include poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes, and tobacco use. 2
Prevention Protocol: Before Starting Therapy
Complete the following dental interventions before initiating bone-modifying agents or anti-angiogenic medications: 1
- Perform comprehensive dental examination with orthopantomography and intraoral radiographs 1
- Complete all necessary dental extractions 1
- Perform all conservative dental and periodontal interventions 1
- Adjust prosthetics to eliminate mucosal trauma 1
- Educate patients about lifelong daily oral hygiene commitment 1
- Perform oral examination prior to sunitinib initiation 4
- Consider dental examination with appropriate preventive dentistry prior to pamidronate treatment in patients with concomitant risk factors 6
Prevention Protocol: During Therapy
Implement the following monitoring schedule for all patients on bone-modifying agents or anti-angiogenic therapy: 1
- Dental follow-up visits every 6 months 1
- Complete dental examination with orthopantomography and intraoral radiographs at each visit 1
- Annual orthopantomography 1
- Evaluation of oral mucosa integrity 1
- Reinforcement of oral hygiene education 1
Management of Dental Procedures During Treatment
Avoid elective dentoalveolar surgery during bone-modifying agent treatment. 1 If dental surgery becomes necessary:
- Coordinate between oncologist and dental specialist 1
- Withhold sunitinib for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures 4
- For pamidronate, patients should avoid invasive dental procedures if possible while on treatment 6
- Do not administer sunitinib for at least 2 weeks following major surgery until adequate wound healing 4
Staging System for MRONJ
The following staging guides treatment decisions: 2
- At risk: No apparent necrotic bone in patients treated with bone-modifying agents 2
- Increased risk: No clinical evidence of necrotic bone but nonspecific clinical findings, radiographic changes, and symptoms 2
- Stage 1: Exposed/necrotic bone or fistulas probing to bone in asymptomatic patients without evidence of infection 2
- Stage 2: Exposed/necrotic bone or fistulas probing to bone with infection (pain, erythema, with/without purulent drainage) 2
- Stage 3: Exposed/necrotic bone or fistulas probing to bone with pain, infection, and one or more of: exposed bone extending beyond alveolar bone, pathologic fracture, extraoral fistula, oral-antral/oral-nasal communication, or osteolysis extending to inferior border of mandible or sinus floor 2
Diagnostic Approach
Perform clinical intraoral examination including direct visual inspection for exposed bone and probing for fistulas that lead to bone. 2
Radiographic evaluation should include: 2
- Panoramic radiographs
- Cone-beam or fan-beam computed tomography
Do not rely solely on radiographic signs for diagnosis, as this may lead to overestimation of disease frequency. 2 Biopsy of suspicious lesions is generally not recommended as it may exacerbate the condition. 2
Management of Established MRONJ
Refer all suspected MRONJ cases to a dental specialist experienced in MRONJ management for staging and treatment. 1
Treatment by Stage
- Stage 1: Conservative therapy with chlorhexidine mouthwash and antimicrobial rinses 1, 7
- Stage 2: Systemic antibiotics (e.g., doxycycline), chlorhexidine mouthwash, and possible limited debridement 1, 7
- Stage 3: Surgical debridement and resection, exodontia of involved teeth, sequestrectomy, and complete surgical debridement of necrotic bone 1, 7
Medication Management During MRONJ
Consider continuation versus discontinuation of bone-modifying agent therapy, balancing cancer treatment needs against MRONJ progression. 1
- Withhold sunitinib for development of ONJ until complete resolution 4
- The safety of resumption of sunitinib after resolution of ONJ has not been established 4
- For pamidronate, if dental surgery is required, it may exacerbate the condition; clinical judgment should guide management based on individual benefit/risk assessment 6
Monitoring During Treatment
Monitor MRONJ with clinical follow-up every 8 weeks by a dental specialist, with communication between dental specialist and oncologist, and regular radiographic assessment to monitor disease progression. 2
Critical Multidisciplinary Communication
Essential communication pathways include: 1
- Oncologist provides dentist with patient's medical diagnosis and complete antiresorptive/angiogenic inhibitor profile 1
- Dentist sends diagnosis and treatment plan to oncologist 1
- Coordinate timing if oral surgery becomes necessary 1
Common Pitfalls and Caveats
- Do not diagnose MRONJ if exposed bone has been present for less than 8 weeks—this may represent normal healing 1, 2
- Distinguish MRONJ from osteoradionecrosis and metastatic disease to the jaws 2
- Even non-surgical periodontal therapy can trigger MRONJ in patients on denosumab, though this is rare 5
- Cone-beam CT may reveal more extensive osteolytic lesions than clinical examination suggests, even in apparent Stage 1 disease 5
- In multiple myeloma patients, the risk of renal dysfunction may be increased when pamidronate is used in combination with thalidomide 6