Update for dentists: Osteonecrosis of the jaw

This paper is an adaptation, with permission, of the recent systematic review published in the Journal of Bone and Mineral Research by the International Task Force on Osteonecrosis of the Jaw.

Archibald Morrison, DDS, MS, FRCD(C); Aliya Khan, MD, FRCPC, FACP, FACE; Sotirios Tetradis, DDS, PhD; Edmund Peters, DDS, MSc, FRCD(C)

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This work provides a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of osteonecrosis of the jaw (ONJ), and offers recommendations for its management based on multidisciplinary international consensus.

Purpose of the review

• To provide a current update on osteonecrosis of the jaw (ONJ). 
• Nine key questions were posed and answered by the task force in the context of this article. These range from definition and staging, incidence and prevalence, how common it is in the osteoporosis and oncologic populations, risk factors to the role of imaging, use of biomarkers to management and newer therapies.
• Some areas are dealt with in detail such as imaging for this disorder since dentistry may be the first line health care discipline to be in a position to image, assess and diagnose ONJ. As well, dentistry needs to be familiar with available management options for these patients since surgical possibilities exist which fall under the umbrella of care of the oral and maxillofacial surgeon.
• Conservative management is discussed as it continues to be a mainstay of ongoing care for many of these unfortunate patients. Insight into newer experimental therapies is highlighted so that dentists will be aware should they read about these methods becoming more mainstream.

Key Findings

ONJ has been renamed BRONJ (bisphosphonate related), ARONJ (antiresorptive related) and more recently MRONJ¹ (medication related); these terms are synonymous with ONJ, which is the preferred nomenclature recommended by the International Task Force.²

Nomenclature, Definition, Risk Factors and Etiology of ONJ

• The condition is presently known to be associated with 2 classes of drugs – bisphosphonates and denosumab. There may also be an association with antiangiogenic agents which requires further investigation.
• The proposed definition of ONJ remains and is: non healing exposed bone of the jaw persisting for 8 weeks in the absence of any previous tumoricidal radiotherapy to the area.²
• In addition to drugs causing ONJ, it is recognized in the published literature that ONJ can develop spontaneously and has been described as lingual mandibular sequestration and ulceration (LMSU).⁷
• A confounding factor in efforts to determine ONJ incidence in those taking oral bisphosphonates is that ONJ cases have been documented in patients with no history of bisphosphonate exposure.
• Three stages of ONJ have been proposed and this classification is currently in use.¹¹ Stage 1 is exposed bone with no infection and otherwise asymptomatic. Stage 2 is exposed bone with evidence of infection with or without purulent discharge. Stage 3 is exposed bone with infection and extension radiographically to the inferior border of the mandible or sinus floor in the maxilla or presence of an extra oral fistula or pathologic fracture.
• A number of risk factors have been identified for ONJ, including antiresorptive drugs, minor oral surgery such as dental extractions and periodontal surgery, concomitant use of steroids, anti-angiogenic agents (used in various cancer therapies) as well as diabetes and perhaps smoking.
• The patients most at risk of developing ONJ are those patients on monthly IV bisphosphonates or high dose sub cutaneously administered denosumab 120 mg monthly.

Role of Imaging

• Radiographic features of ONJ remain relatively non-specific. Plain film radiography is usually unremarkable in the early stages of the disease as decalcification is limited.²⁹
• The presence of localized or diffuse osteosclerosis or a thickening of the lamina dura on plain film imaging may predict future sites of exposed necrotic bone.²⁹ Poor ossification at a previous extraction site may also be an early radiographic feature of ONJ.
• Findings on computed tomography (CT) are non-specific and may include areas of focal sclerosis, thickened lamina dura, early sequestrum formation and reactive periosteal bone.^30-33 CT imaging is of value in delineating the extent of disease and is helpful in planning surgical intervention.^31,34 Features noted on bone scanning include increased tracer uptake at sites which subsequently develop necrosis.³⁵
• Imaging modalities used as adjunctive assessment in the evaluation of the ONJ patient may include plain radiographs, CT, magnetic resonance imaging (MRI) and functional imaging with bone scintigraphy and positron emission tomography (PET).

Recommendations for Imaging

• Individuals on low dose anti-resorptive treatment without signs or symptoms of ONJ do not require any additional imaging beyond routine dental evaluation.^68-70
• Patients on high-dose anti-resorptive treatment without ONJ are at significant risk of developing ONJ and early identification of dental disease is important.^63,64 
• In patients in whom ONJ is a clinical consideration on low or high dose anti-resorptive therapy presenting with oral symptoms CBCT or CT imaging may aid in evaluating early changes in the cortical and trabecular architecture of the maxilla and mandible. 
• CBCT may be performed in conjunction with bitewing, periapical and panoramic radiographs. If clinically indicated, MRI may provide additional information of the presence and extent of osteonecrosis.
• Patients with clinical ONJ under conservative management (Stage 1 and 2). The nature and extent of osseous changes around the area of clinical bone exposure can be evaluated with CT or CBCT imaging. 
• In patients with clinical ONJ where surgical intervention is considered (Stage 2 and 3), CBCT or CT may be complemented with MRI, bone scan or PET for a more thorough evaluation of involved bone and soft tissues.

ONJ and Dental Management

• It is important for dental patients at risk of developing ONJ to maintain meticulous oral hygiene and regular dental visits. Any surgical therapy should be minimized and especially if non surgery is an option – endodontics versus extraction for example.
• Any minor oral surgery including extractions and periodontal surgery should include antibiotic prophylaxis, both systemic and topical, careful surgical technique, minimizing sharp bony edges and providing primary closure over bony wounds wherever possible.
• There is no need for interruption of oral bisphosphonate therapy such as that taken for osteoporosis therapy, either before or after the minor surgical procedure.
• For those on high dose IV bisphosphonate or denosumab therapy or with multiple risk factors for ONJ it is recommended that the antiresorptive therapy be withheld following the oral surgery until the surgical site has healed with mature soft tissue closure over the wound. 

Managing ONJ

• A patient with ONJ that is failing conservative therapy or whose ONJ is progressing should be referred to and managed by an oral and maxillofacial surgeon.
• For Stages 1 and 2, conservative therapy may be all that is required. Meticulous oral hygiene, preventive care, topical antibiotic rinses such as chlorhexidine and periodic systemic antibiotics should be used as needed.

Conclusion

• Spontaneous resolution of ONJ is possible. Early treatment recommendations discouraged surgical intervention, with conservative therapy continuing indefinitely or until there was progression of disease. Others have had reasonable success with surgical management.^72,73
• There is still no comfortable proven treatment algorithm for the various stages of this disease.
• The International Task Force believes that surgical intervention is required for Stage 3 disease and for those Stage 2 patients that are showing progression or require continual antibiotic or narcotic analgesic therapy in order to control their symptoms.