title: Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis.
abstract: BACKGROUND
  Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare claims.
  
  
  METHODS
  We identified 16,073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28,698 bisphosphonate nonusers, at a 2:1 ratio, to 14,349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first.
  
  
  RESULTS
  Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95% CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95% CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95% CI = 1.74 to 48.53).
  
  
  CONCLUSIONS
  Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1153, USA. gswilkin@utmb.edu
authors.forename: Gregg S
authors.initials: GS
authors.lastname: Wilkinson
authors.forename: Yong-Fang
authors.initials: YF
authors.lastname: Kuo
authors.forename: Jean L
authors.initials: JL
authors.lastname: Freeman
authors.forename: James S
authors.initials: JS
authors.lastname: Goodwin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001842:Bone and Bones / Q000473:pathology; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000453:epidemiology*; D007571:Jaw Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology* / Q000601:surgery; D008297:Male; D006278:Medicare; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D010020:Osteonecrosis / Q000473:pathology; D018426:SEER Program; D014481:United States
chemical_list: D004164:Diphosphonates