title: The national-scale cohort study on bisphosphonate-related osteonecrosis of the jaw in Taiwan.
abstract: OBJECTIVE
  Osteonecrosis of the jaw (ONJ) is a potential side effect of bisphosphonate therapy. This Taiwanese national-scale cohort study aimed to investigate its incidence and risk of development by using a qualified control group with different demographic factors (age/gender), dental (tooth extraction/periodontal therapy) and medical (jaw radiotherapy) treatments, delivery routes (oral/intravenous), and diseases (diabetes/osteoporosis/cancer).
  
  
  METHODS
  Data (n=958,136) from January 1, 2006 through December 31, 2008 were sourced from the Longitudinal Health Insurance Database 2005 of Taiwan. Cases of BRONJ were identified by three criteria modified from the definition proposed by the American Association of Oral and Maxillofacial Surgeons. The Cox proportional-hazards regression model and Kaplan-Meier estimates were used to analyse the results.
  
  
  RESULTS
  The incidence densities of ONJ in the unexposed and bisphosphonate-exposed cohorts were estimated as 4.4 and 73.5 per 100,000 person-years, respectively (relative risk=16.8; 95% CI=6.0-37.5; P<0.001). Multivariate analysis revealed strong associations of delivery route, tooth extraction, and oral cancer with ONJ (hazard ratios=51.4 for oral bisphosphonates, 153.3 for intravenous bisphosphonates, 5.3 for tooth extraction, and 278.1 for oral cancer).
  
  
  CONCLUSIONS
  These results not only demonstrate the incidence and relative risk of bisphosphonate-related ONJ in Taiwan but also indicate that tooth extraction and oral cancer may have a major impact on its development.
  
  
  CONCLUSIONS
  Physicians should be aware of individual patient risk factors before prescribing bisphosphonates. Bisphosphonate treatment is justified in the amelioration of life-threatening conditions in patients in whom ONJ would only affect quality of life.
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Da-Yo
authors.initials: DY
authors.lastname: Yuh
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Ting-Han
authors.initials: TH
authors.lastname: Chang
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Ren-Yeong
authors.initials: RY
authors.lastname: Huang
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wu-Chien
authors.initials: WC
authors.lastname: Chien
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Fu-Gong
authors.initials: FG
authors.lastname: Lin
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan. Electronic address: ndmcearl@ndmctsgh.edu.tw.
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
mesh_terms: D061605:Administration, Intravenous / Q000706:statistics & numerical data; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015994:Incidence; D007568:Jaw / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology; D010024:Osteoporosis / Q000453:epidemiology; D010510:Periodontal Diseases / Q000453:epidemiology; D011159:Population Surveillance; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000706:statistics & numerical data; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014081:Tooth Extraction / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: Bisphosphonate-related osteonecrosis of the jaw; Cox proportional hazards models; Database; Health insurance; Kaplan–Meier estimate; Taiwan