Medication-related osteonecrosis of the jaw (MRONJ) describes the bony destruction of the jaw (the mandible is more commonly involved than the 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.
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Terminology
"Bisphosphonate-related osteonecrosis of the jaw (BRONJ)" was the initially described entity, but "medication-related osteonecrosis of the jaw" is now the preferred term as other medications besides bisphosphonates have been implicated as etiological agents 5,6.
It should also be noted that, although less common, the maxilla can also be affected 7.
Epidemiology
Medication-related osteonecrosis of the jaw 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 1 although this likely represents the population receiving bisphosphonates 3.
Risk factors
treatment for malignancy is a greater risk than osteoporosis
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recent dental surgery: mainly tooth extraction (~65% of patients) 2,3,10
risk seems to be higher for cancer than osteoporosis patients 10
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 2,3
long-term bisphosphonate use 3
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dual pharmacy
risk higher if on a bisphosphonate and antiangiogenic therapy simultaneously 10
concurrent bone metastases or multiple myeloma 1,2
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dental or periodontal disease 3
injury from poorly fitting dentures
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additional possible risk factors in those with cancer 10
Clinical presentation
Medication-related osteonecrosis of the jaw is a painful process and before osteonecrosis becomes clearly evident the patient may present with the following symptoms and signs 2:
periodontal disease and non-healing mucosal ulcers
loose teeth
soft tissue infections
Established medication-related osteonecrosis of the jaw manifests as necrosis of the jaw with exposed bone.
Pathology
The definite pathogenesis of medication-related osteonecrosis of the jaw has not yet been established but is proposed to be related to bone remodeling suppression and antiangiogenic effects of these medications 3.
Medications implicated in the formation of medication-related osteonecrosis of the jaw include 5,6,8-11:
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indicated for osteoporosis
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bisphosphonates
IV: zoledronate, ibandronate, pamidronate
oral: alendronate, risedronate, clodronate
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RANKL inhibitor monoclonal antibody
denosumab
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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
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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 1,2.
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 7.
Radiographic features
Plain radiograph
Plain films and OPGs may not demonstrate early disease 1,3. When visible, features are non-specific and include 1,7:
poorly defined lucent, mixed or sclerotic lesion
destruction of adjacent structures
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
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treatment is primarily palliative
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treat superadded infection, bone necrosis, mitigate pain
fastidious dental hygiene: including mouthwashes +/- antimicrobials
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surgery is generally to be avoided as it may aggravate the necrosis 10
Differential diagnosis
radiation necrosis of the jaw (mandibular osteoradionecrosis): virtually indistinguishable clinically and radiologically 2