title: Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.
abstract: Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.
authors.affiliation: Department of Medicine, Divisions of Endocrinology and Metabolism and Geriatrics, McMaster University, Hamilton, ON, Canada. Electronic address: Aliya@mcmaster.ca.
authors.forename: Aliya A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Division of Oral and Maxillofacial Surgery, Dalhousie University, Halifax, NS, Canada.
authors.forename: Archie
authors.initials: A
authors.lastname: Morrison
authors.affiliation: Department of Medicine, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.affiliation: Division of Bone Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Rene
authors.initials: R
authors.lastname: Rizzoli
authors.affiliation: Departments of Medicine, Community Health Sciences and Oncology, University of Calgary, Calgary, AB, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.affiliation: Centre of Muscle & Bone Research, Charité-University Medicine Berlin, Campus Benjamin Franklin, Free University & Humboldt University Berlin, Berlin, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Felsenberg
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.affiliation: Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, Oakland, CA, USA.
authors.forename: Felice
authors.initials: F
authors.lastname: O'Ryan
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.affiliation: Division of Oral and Maxillofacial Surgery, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA; Stony Brook School of Dental Medicine, Stony Brook, NY, USA; New York Center for Orthognathic and Maxillofacial Surgery, New York, NY, USA.
authors.forename: Salvatore L
authors.initials: SL
authors.lastname: Ruggiero
authors.affiliation: Department of Oral and Maxillofacial Radiology, School of Dentistry, Matsumoto Dental University, Shojiri, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tetradis
authors.affiliation: Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA.
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Watts
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Edmund
authors.initials: E
authors.lastname: Peters
authors.affiliation: Department of Medicine, Division of Endocrinology at Indiana University, Indianapolis, IN, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Guise
authors.affiliation: Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada; Centre of Excellence in Skeletal Health Assessment, Joint Department of Medical Imaging, University Health Network (UHN), Toronto, ON, Canada; Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.affiliation: Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Morin
authors.affiliation: Jordan Osteoporosis Center, Jordan Hospital & Medical Center, Amman, Jordan.
authors.forename: Basel
authors.initials: B
authors.lastname: Masri
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham Osteoporosis Prevention and Treatment Clinic, Birmingham, AL, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Morgan
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.affiliation: Faculty of Dentistry, University of Toronto, Toronto, Canada.
authors.forename: Rana Al
authors.initials: RA
authors.lastname: Dabagh
authors.affiliation: Department of Education, University of Victoria,Victoria, BC, Canada.
authors.forename: K Shawn
authors.initials: KS
authors.lastname: Davison
authors.affiliation: Department of Oral and Maxillofacial Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: George K
authors.initials: GK
authors.lastname: Sándor
authors.affiliation: Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Josse
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Bhandari
authors.affiliation: Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Rabbany
authors.affiliation: International Osteoporosis Foundation (IOF), Nyon, Switzerland.
authors.forename: Dominique D
authors.initials: DD
authors.lastname: Pierroz
authors.affiliation: College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Riad
authors.initials: R
authors.lastname: Sulimani
authors.affiliation: Department of Dental Oncology, Northeast Cancer Centre/Health Science North, Sudbury, ON, Canada.
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Saunders
authors.affiliation: Rheumatology Division, CHU de Québec Research Centre, Laval University, Quebec City, QC, Canada.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.affiliation: Department of Medicine, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
mesh_terms: D026683:Advisory Committees; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy*; D003646:Debridement; D000069448:Denosumab / Q000008:administration & dosage / Q000009:adverse effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D009910:Oral Hygiene / Q000379:methods; D010024:Osteoporosis / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000517:prevention & control*; D010510:Periodontal Diseases / Q000453:epidemiology* / Q000628:therapy; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D019379:Teriparatide / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019379:Teriparatide; D000069448:Denosumab
keywords: Bisphosphonates; denosumab; diagnosis; management; osteonecrosis of the jaw