title: Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed.
abstract: Recent data suggest that the traditional definition of bisphosphonate-associated osteonecrosis of the jaw (ONJ) may exclude patients who present with the non-exposed variant of the condition. To test the hypothesis that a proportion of patients with ONJ remain undiagnosed because their symptoms do not conform to the traditional case definition, we did a secondary analysis of data from MISSION (Multicentre study on phenotype, definition and classification of osteonecrosis of the jaws associated with bisphosphonates), a cross-sectional study of a large population of patients with bisphosphonate-associated ONJ who were recruited in 13 European centres. Patients with exposed and non-exposed ONJ were included. The main aim was to quantify the proportion of those who, according to the traditional case definition, would not be diagnosed with ONJ because they had no exposed necrotic bone. Data analysis included descriptive statistics, median regression, and Fisher's exact test. A total of 886 consecutive patients were recruited and 799 were studied after data cleaning (removal or correction of inaccurate data). Of these, 607 (76%) were diagnosed according to the traditional definition. Diagnosis in the remaining 192 (24%) could not be adjudicated, as they had several abnormal features relating to the jaws but no visible necrotic bone. The groups were similar for most of the phenotypic variables tested. To our knowledge this is the first study in a large population that shows that use of the traditional definition may result in one quarter of patients remaining undiagnosed. Those not considered to have ONJ had the non-exposed variant. These findings show the importance of adding this description to the traditional case definition.
authors.affiliation: University College London, UCL Eastman Dental Institute and NIHR University College London Hospitals Biomedical Research Centre, London, UK. Electronic address: s.fedele@ucl.ac.uk.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fedele
authors.affiliation: Liver Research Centre, Clinical Epidemiology Unit, Basovizza, Trieste, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bedogni
authors.affiliation: University of Turin, Department of Biomedical Science and Human Oncology, Section of Oral Medicine, UNITO Lingotto Dental Institute, Turin, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Scoletta
authors.affiliation: University of Bari, Department of Odontostomatology and Surgery, Bari, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Favia
authors.affiliation: Second University of Naples, Department of Medical, Surgical and Dental Specialties, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colella
authors.affiliation: University "La Sapienza", Department of Oral and Maxillofacial Sciences, Section of Maxillofacial Surgery, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Agrillo
authors.affiliation: University Hospital of Padova, Department of Neurosciences, Unit of Oral and Maxillofacial Surgery, Padova, Italy.
authors.forename: Giordana
authors.initials: G
authors.lastname: Bettini
authors.affiliation: University of Palermo, Department of Surgical, Oncological and Oral Sciences, Sector of Oral Medicine, Palermo, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Di Fede
authors.affiliation: University of Messina, Department of Odontostomatology, Messina, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Oteri
authors.affiliation: Hospital "SS. Antonio, Biagio and C. Arrigo", Department of Oncology and Haematology, Unit of Medical Oncology, Alessandria, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fusco
authors.affiliation: University of Pisa, Department of Surgery, Section of Dentistry and Oral Surgery, Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Gabriele
authors.affiliation: University "La Sapienza", Department of Oral and Maxillofacial Sciences, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Ottolenghi
authors.affiliation: Hospital S. Anna, Unit of Maxillofacial Surgery, Como, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Valsecchi
authors.affiliation: University College London, UCL Eastman Dental Institute, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Porter
authors.affiliation: University College London, UCL Eastman Dental Institute, London, UK.
authors.forename: Polly Pok-Lam
authors.initials: PP
authors.lastname: Fung
authors.affiliation: University Hospital of Padova, Department of Neurosciences, Unit of Oral and Maxillofacial Surgery, Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Saia
authors.affiliation: University of Palermo, Department of Surgical, Oncological and Oral Sciences, Sector of Oral Medicine, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.affiliation: University and Hospital Trust of Verona, Department of Surgery, Section of Oral and Maxillofacial Surgery, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bedogni
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000145:classification / Q000175:diagnosis*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D057210:Delayed Diagnosis; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D010147:Pain Measurement / Q000379:methods; D010510:Periodontal Diseases / Q000175:diagnosis; D010641:Phenotype; D014076:Tooth Diseases / Q000175:diagnosis; D014081:Tooth Extraction
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents
keywords: Bisphosphonates; Jawbones; Osteonecrosis