title: 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, ill-fitting 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.
authors.forename: Aliya A
authors.initials: AA
authors.lastname: Khan
authors.forename: Archie
authors.initials: A
authors.lastname: Morrison
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.forename: Dieter
authors.initials: D
authors.lastname: Felsenberg
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.forename: Felice
authors.initials: F
authors.lastname: O'Ryan
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Salvatore L
authors.initials: SL
authors.lastname: Ruggiero
authors.forename: Akira
authors.initials: A
authors.lastname: Taguchi
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tetradis
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Watts
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Edmund
authors.initials: E
authors.lastname: Peters
authors.forename: Teresa
authors.initials: T
authors.lastname: Guise
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Morin
authors.forename: Basel
authors.initials: B
authors.lastname: Masri
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Morgan
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: Rana
authors.initials: R
authors.lastname: Al Dabagh
authors.forename: K Shawn
authors.initials: KS
authors.lastname: Davison
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.forename: George K
authors.initials: GK
authors.lastname: Sándor
authors.forename: Robert G
authors.initials: RG
authors.lastname: Josse
authors.forename: Mohit
authors.initials: M
authors.lastname: Bhandari
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Rabbany
authors.forename: Dominique D
authors.initials: DD
authors.lastname: Pierroz
authors.forename: Riad
authors.initials: R
authors.lastname: Sulimani
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Saunders
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D001424:Bacterial Infections / Q000276:immunology; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology / Q000628:therapy; D054893:Cone-Beam Computed Tomography; D000069448:Denosumab; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008334:Mandible / Q000000981:diagnostic imaging / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010024:Osteoporosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000069448:Denosumab
keywords: BISPHOSPHONATES; DENOSUMAB; DIAGNOSIS; IMAGING; MANAGEMENT; OSTEONECROSIS OF THE JAW; RISK FACTORS; TREATMENT