Medication-related osteonecrosis of the jaw (MRONJ) describes the bony destruction of the jaw 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.
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 5,6.
It should also be noted that, although less common, the maxilla can also be affected 7.
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 1 although this likely represents the population receiving bisphosphonates 3.
MRONJ 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 MRONJ manifests as necrosis of the jaw with exposed bone.
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 3.
Medications implicated in the formation of MRONJ include 5,6,8-11:
- indicated for osteoporosis
- IV: zoledronate, ibandronate, pamidronate
- oral: alendronate, risedronate, clodronate
- RANKL inhibitor monoclonal antibody
- 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
- anti-TNF agents
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.
- treatment for malignancy is a greater risk than osteoporosis
- 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
- dual pharmacy
- risk higher if on a bisphosphonate and antiangiogenic therapy simultaneously 10
- concurrent bone metastases or multiple myeloma 1,2
- dental or periodontal disease 3
- injury from poorly fitting dentures
- additional possible risk factors in those with cancer 10
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
- periosteal proliferation
- destruction of adjacent structures
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
- treat superadded infection, bone necrosis, mitigate pain
- surgery is generally to be avoided as it may aggravate the necrosis 10
- radiation necrosis of the jaw (mandibular osteoradionecrosis): virtually indistinguishable clinically and radiologically 2
- 1. Haworth AE, Webb J. Skeletal complications of bisphosphonate use: what the radiologist should know. Br J Radiol. 2012;85 (1018): 1333-42. doi:10.1259/bjr/99102700 - Free text at pubmed - Pubmed citation
- 2. Ficarra G, Beninati F. Bisphosphonate-related osteonecrosis of the jaws: an update on clinical, pathological and management aspects. Head Neck Pathol. 2007;1 (2): 132-40. doi:10.1007/s12105-007-0033-2 - Free text at pubmed - Pubmed citation
- 3. Ruggiero SL. Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Clin Cases Miner Bone Metab. 2012;4 (1): 37-42. Free text at pubmed - Pubmed citation
- 4. Vescovi P, Nammour S. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review. Minerva Stomatol. 2010;59 (4): 181-203, 204-13. Pubmed citation
- 5. Katsarelis H, Shah NP, Dhariwal DK et-al. Infection and medication-related osteonecrosis of the jaw. J. Dent. Res. 2015;94 (4): 534-9. doi:10.1177/0022034515572021 - Pubmed citation
- 6. Ruggiero SL, Dodson TB, Fantasia J et-al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J. Oral Maxillofac. Surg. 2014;72 (10): 1938-56. doi:10.1016/j.joms.2014.04.031 - Pubmed citation
- 7. Andreu-Arasa VC, Chapman MN, Kuno H, Fujita A, Sakai O. Craniofacial Manifestations of Systemic Disorders: CT and MR Imaging Findings and Imaging Approach. (2018) Radiographics : a review publication of the Radiological Society of North America, Inc. 38 (3): 890-911. doi:10.1148/rg.2018170145 - Pubmed
- 8. Rosella D, Papi P, Giardino R, Cicalini E, Piccoli L, Pompa G. Medication-related osteonecrosis of the jaw: Clinical and practical guidelines. (2016) Journal of International Society of Preventive & Community Dentistry. 6 (2): 97-104. doi:10.4103/2231-0762.178742 - Pubmed
- 9. Kim DW, Jung YS, Park HS, Jung HD. Osteonecrosis of the jaw related to everolimus: a case report. (2013) The British journal of oral & maxillofacial surgery. 51 (8): e302-4. doi:10.1016/j.bjoms.2013.09.008 - Pubmed
- 10. Zebic L, Patel V. Preventing medication-related osteonecrosis of the jaw. (2019) BMJ (Clinical research ed.). 365: l1733. doi:10.1136/bmj.l1733 - Pubmed
- 11. Pimolbutr K, Porter S, Fedele S. Osteonecrosis of the Jaw Associated with Antiangiogenics in Antiresorptive-Naïve Patient: A Comprehensive Review of the Literature. (2018) BioMed research international. 2018: 8071579. doi:10.1155/2018/8071579 - Pubmed
- 12. Obinata K, Shirai S, Ito H, Nakamura M, Carrozzo M, Macleod I, Carr A, Yamazaki Y, Tei K. Image findings of bisphosphonate related osteonecrosis of jaws comparing with osteoradionecrosis. (2017) Dento maxillo facial radiology. 46 (5): 20160281. doi:10.1259/dmfr.20160281 - Pubmed