title: Bisphosphonate-related osteonecrosis of the jaws - characteristics, risk factors, clinical features, localization and impact on oncological treatment.
abstract: BACKGROUND
  Osteonecrosis of the jaw (ONJ) is a serious side-effect of intravenous nitrogen-containing bisphosphonate therapy frequently used in the treatment of malignant diseases. Despite numerous case series published so far studies with detailed investigations into risk factors, the precise localization of ONJ and impact of ONJ on the oncological treatment remain sparse.
  
  
  METHODS
  This single-centre study collated medical records (2003-2009) of all patients that suffered from ONJ within the Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Germany. In total, 126 patients fulfilled the case criteria of ONJ and were examined clinically. The complete medical history including detailed questionnaires was collected of 66 patients, focussing in particular on the identification of underlying risk factors, clinical features, ONJ localization as well as the impact on the oncological treatment.
  
  
  RESULTS
  The majority of ONJ cases occurred in patients suffering from malignant diseases (n=117; 92.8%), in particular breast cancer (n=57; 45.2%), multiple myeloma (n=37; 29.4%) and prostate cancer (n=13; 10.3%), all received nitrogen-containing bisphosphonates intravenously. ONJ was also diagnosed in 9 patients (7.1%) suffering from osteoporosis or rheumatoid arthritis. The most prevalent clinical feature was exposed necrotic bone (93.9%) in the oral cavity which was accompanied in 78.8% of cases by pain. A predilection for the mandible and in particular for molar and premolar regions in both jaws was shown. Although no recommendation concerning the oncologic treatment was made, the manifestation of ONJ resulted (in a significant proportion of the patients) in a change of medication and schedule. The most frequent co-medications were steroids and anti-angiogenetic drugs, such as thalidomide.
  
  
  CONCLUSIONS
  The predilection for mandibular molar and premolar regions, and the infectious conditions that often precede the onset of ONJ support recent pathogenesis theories stating that local inflammation and associated pH-changes may trigger the release and activation of nitrogen-containing bisphosphonates ultimately resulting in necrosis.
  
  
  CONCLUSIONS
  The development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University, Munich, Germany. Sven.Otto@med.uni-muenchen.de
authors.forename: Sven
authors.initials: S
authors.lastname: Otto
authors.forename: Christian
authors.initials: C
authors.lastname: Schreyer
authors.forename: Sigurd
authors.initials: S
authors.lastname: Hafner
authors.forename: Gerson
authors.initials: G
authors.lastname: Mast
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrenfeld
authors.forename: Stephen
authors.initials: S
authors.lastname: Stürzenbaum
authors.forename: Christoph
authors.initials: C
authors.lastname: Pautke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001641:Bicuspid; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000175:diagnosis / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D003724:Dental Arch / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008336:Mandibular Diseases / Q000139:chemically induced; D008875:Middle Aged; D008963:Molar; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D010024:Osteoporosis / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D020533:Angiogenesis Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D013792:Thalidomide