What are the diagnostic criteria and management options for osteonecrosis of the jaw?

Diagnostic Criteria for Osteonecrosis of the Jaw (ONJ)

To diagnose osteonecrosis of the jaw (ONJ), clinicians must confirm the presence of all three of the following criteria: (1) current or previous treatment with a bone-modifying agent (BMA) or angiogenic inhibitor, (2) exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for longer than 8 weeks, and (3) no history of radiation therapy to the jaws or metastatic disease to the jaws. 1

Definition and Terminology

• The recommended term for this condition is "medication-related osteonecrosis of the jaw" (MRONJ) when referring to bone necrosis associated with pharmacologic therapies 1
• MRONJ can involve either the mandible or the maxilla 1
• The condition is characterized by exposed bone or bone that can be probed through a fistula in the maxillofacial region that does not heal within 8 weeks 1

Risk Factors and Associated Medications

• BMAs that have been linked with MRONJ primarily include:
  • Bisphosphonates (e.g., zoledronic acid, pamidronate) 1
  • Denosumab 1, 2
• Angiogenic inhibitors (including tyrosine kinase inhibitors) have also been associated with ONJ 3
• MRONJ occurs in approximately 1% to 9% of patients with advanced cancer receiving BMAs 1
• Modifiable risk factors that increase MRONJ risk include:
  • Poor oral health 1
  • Invasive dental procedures (particularly extractions) 1, 4
  • Ill-fitting dentures 1
  • Uncontrolled diabetes mellitus 1
  • Tobacco use 1

Diagnostic Approach

Initial Evaluation

• Clinical intraoral examination including:
  • Direct visual inspection for exposed bone 1
  • Probing for fistulas that lead to bone 1
  • Assessment of symptoms (pain, swelling, purulent drainage) 1
• Radiographic examination:
  • Panoramic radiographs (orthopantomogram) 1
  • Cone-beam or fan-beam computed tomography when available 1
  • Magnetic resonance imaging when indicated 1

Staging System

MRONJ should be staged according to the following classification 1:

• At risk: No apparent necrotic bone in patients treated with BMAs
• Increased risk: No clinical evidence of necrotic bone but nonspecific clinical findings, radiographic changes, and symptoms
• Stage 1: Exposed/necrotic bone or fistulas probing to bone in asymptomatic patients without evidence of infection
• Stage 2: Exposed/necrotic bone or fistulas probing to bone with infection (pain, erythema, with/without purulent drainage)
• 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 1

Diagnostic Pitfalls and Caveats

• Do not rely solely on radiographic signs for diagnosis of MRONJ, as this may lead to overestimation of disease frequency 1
• Distinguish MRONJ from other conditions that may present similarly:
  • Osteoradionecrosis (history of radiation therapy to the jaws) 1
  • Metastatic disease to the jaws 1
  • Osteomyelitis of different etiology 4
• The 8-week timeframe for non-healing exposed bone is critical for diagnosis - shorter durations may represent normal healing processes 1
• Stage 0 MRONJ (nonspecific symptoms without exposed bone) has been described but remains controversial for definitive diagnosis 5
• Biopsy of suspicious lesions is generally not recommended as it may exacerbate the condition 1

Monitoring and Follow-up

• Once diagnosed, MRONJ should be monitored with:
  • Clinical follow-up every 8 weeks by a dental specialist 1
  • Communication between dental specialist and oncologist regarding lesion status (resolved, improving, stable, or progressive) 1
  • Regular radiographic assessment to monitor disease progression 1

By following these diagnostic criteria and staging system, clinicians can accurately diagnose MRONJ and implement appropriate management strategies to minimize morbidity and improve quality of life for affected patients.