Medication-related osteonecrosis of the jaw

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Medication-related osteonecrosis of the jaw (MRONJ) describes the bony destruction of the jaw (mandible > maxilla) with exposed bone present for greater than eight weeks in the presence of current or previous antiresorptive and/or antiangiogenic medication use, and in the absence of radiation therapy to the head and neck or obvious metastatic disease.

Terminology

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) was the initially described entity, but MRONJ is now the preferred term as other medications besides bisphosphonates have been implicated as etiological agents .

It should also be noted that, although less common, the maxilla can also be affected .

Epidemiology

MRONJ is estimated to affect 1 in 10,000 to 100,000 in a patient taking oral bisphosphonates. It more commonly affects females and patients older than 60 years although this likely represents the population receiving bisphosphonates .

Clinical presentation

MRONJ is a painful process and before osteonecrosis becomes clearly evident the patient may present with the following symptoms and signs :

  • periodontal disease and non-healing mucosal ulcers
  • loose teeth
  • soft tissue infections

Established MRONJ manifests as necrosis of the jaw with exposed bone.

Pathology

The definite pathogenesis of MRONJ has not yet been established but is proposed to be related to bone remodeling suppression and antiangiogenic effects of these medications .

Medications implicated in the formation of MRONJ include :

  • indicated for osteoporosis
    • bisphosphonates
      • IV: zoledronate, ibandronate, pamidronate
      • oral: alendronate, risedronate, clodronate
    • RANKL inhibitor monoclonal antibody
      • denosumab
  • indicated for malignancy or immunosuppression
    • tyrosine kinase inhibitors (TKI) e.g. sunitinib, sorafenib, pazopanib
    • VEGF inhibitor: bevacizumab (humanised monoclonal antibody)
    • mTOR inhibitors, e.g. sirolimus, everolimus, temsirolimus
    • fusion protein: aflibercept
  • other therapies of less certainty
    • radium-223
    • anti-TNF agents
Location

The mandible is affected more commonly than the maxilla (2:1), and they can be involved independently or simultaneously .

As impairment of normal bone remodeling and healing is the postulated mechanism, it is not surprising that the areas most frequently involved are those most likely to have trauma in the form of tooth extraction or the alveolar ridge in edentulous individuals .

Risk factors
  • treatment for malignancy is a greater risk than osteoporosis
  • recent dental surgery: mainly tooth extraction (~65% of patients)
    • risk seems to be higher for cancer than osteoporosis patients
    • if a patient is to be started on high-dose/IV bisphosphonate treatment then ideally any planned dental work should be done prior to this to minimize risk
  • IV bisphosphonate use
  • long-term bisphosphonate use
  • dual pharmacy
    • risk higher if on a bisphosphonate and antiangiogenic therapy simultaneously
  • concurrent bone metastases or multiple myeloma
  • dental or periodontal disease
    • injury from poorly fitting dentures
  • additional possible risk factors in those with cancer

Radiographic features

Plain radiograph

Plain films and OPGs may not demonstrate early disease .  When visible, features are non-specific and include :

CT

In addition to the aforementioned plain radiographic findings, CT is more likely to demonstrate early changes:

  • prominence of the periodontal ligament
  • focal sclerosis adjacent to the root of a tooth
  • periosteal reaction

Treatment and prognosis

  • specialist maxillofacial/dental management of medication-related osteonecrosis of the jaw is essential
  • treatment is primarily palliative
    • treat superadded infection, bone necrosis, mitigate pain
      • fastidious dental hygiene: including mouthwashes +/- antimicrobials
  • surgery is generally to be avoided as it may aggravate the necrosis

Differential diagnosis

See also