Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus

Abstract

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. ONJ is associated with oncology-dose parenteral antiresorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1% to 15%), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%). New insights into the pathophysiology of ONJ include antiresorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, illfitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced nonresponsive disease and has been successful. Early data have suggested enhanced osseous wound healing with teriparatide in those without contraindications for its use. Experimental therapy includes bone marrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.

The use of low-level light therapy in supportive care for patients with breast cancer: review of the literature

“…Up to now, there is no standard treatment strategy for MRONJ and every case has to be treated individually. However, the AAOMS has made some recommendations depending on the stage of the disease ranging from pain management, use of antibiotics, antimicrobial mouth rinses, wound debridement, to surgical interventions (e.g., removal of sharp bone structures) [67][68][69].…”

Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma in Older Adults

“…A recent set of guidelines covers this topic at length. 58 Most patients with MM but not hypercalcemia should take calcium and vitamin D supplementation for bone health. 59 Support through cytopenias is similar to that given to younger patients with MM and similar strategies using chemotherapy dose reductions/omissions, growth factors, and/or transfusions can be used.…”

Osteoporosis: recent advances in diagnosis and management

“…9 In the UK there is a move towards adopting 20 per cent risk for any osteoporotic fracture and 5 per cent for hip fracture. Fixed treatment thresholds for people in the UK are attractive as they are easy to use and allow clear division into low risk (less than 10 per cent for any fracture and 3 per cent for hip fracture), intermediate risk (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) per cent for any fracture and 3-5 per cent for hip fracture) and high risk (>20 per cent for any and >5 per cent for hip fracture). In the absence of national guidance, the decision as to which treatment threshold to use needs to be agreed locally.…”

“…It is thought that the risk of ONJ can be reduced by patients undergoing any necessary dental treatment before starting these medications. 19 AFFs are atraumatic or low-trauma fractures in the subtrochanteric and diaphyseal regions of the femur that have been reported in people on long-term bisphosphonates and denosumab 20 (see Figure 3). They arise in the lateral cortex, have an unusual transverse/short oblique configuration and can be bilateral.…”

“…Patients on these medications should be advised to report any hip, groin or thigh pain, which may indicate such a fracture. However, a causal association between osteoporosis medications and AFF has not been proven, 19,20 and the number of fragility fractures prevented by bisphosphonate therapy far outweighs the number of AFFs that occur.…”