Medication-Related Osteonecrosis of the Jaw—2014 Update

Background. This narrative review of osteonecrosis of the jaw in patients with low bone mass receiving treatment with antiresorptive agents is based on an appraisal of the literature by an advisory committee of the American Dental Association Council on Scientific Affairs. It updates the committee’s 2008 advisory statement. Methods. The authors searched MEDLINE for literature published between May 2008 (the end date of the last search) and February 2011. Results. This report contains recommendations based on the findings of the literature search and on expert opinion that relate to general dentistry; periodontal disease management; implant placement and maintenance; oral and maxillofacial surgery; endodontics; restorative dentistry and prosthodontics; orthodontics; and C-terminal telopeptide testing and drug holidays. Conclusions. The highest reliable estimate of antiresorptive agent– induced osteonecrosis of the jaw (ARONJ) prevalence is approximately 0.10 percent. Osteoporosis is responsible for considerable morbidity and mortality. Therefore, the benefit provided by antiresorptive therapy outweighs the low risk of developing osteonecrosis of the jaw. Clinical Implications. An oral health program consisting of sound hygiene practices and regular dental care may be the optimal approach for lowering ARONJ risk. No validated diagnostic technique exists to determine which patients are at increased risk of developing ARONJ. Discontinuing bisphosphonate therapy may not lower the risk but may have a negative effect on low-bone-mass–treatment outcomes. 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, in ﬂ ammation, 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 ﬁ lms often suf ﬁ ce. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic in ﬂ ammation, diabetes mellitus, ill- ﬁ tting 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. © 2014 American Society for Bone and Mineral Research.