title: A retrospective study evaluating frequency and risk factors of osteonecrosis of the jaw in 576 cancer patients receiving intravenous bisphosphonates.
abstract: OBJECTIVE
  To evaluate the frequency, risk factors, and clinical presentation of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ).
  
  
  METHODS
  We performed a retrospective analysis of 576 patients with cancer treated with intravenous pamidronate and/or zoledronate between January, 2003 and December, 2007 at the University of Minnesota Masonic Cancer Center and Park Nicollet Institute.
  
  
  RESULTS
  Eighteen of 576 identified patients (3.1%) developed BRONJ including 8 of 190 patients (4.2%) with breast cancer, 6 of 83 patients (7.2%) with multiple myeloma, 2 of 84 patients (2.4%) with prostate cancer, 1 of 76 patients (1.3%) with lung cancer, 1 of 52 patients (1.9%) with renal cell carcinoma, and in none of the 73 patients with other malignancies. Ten patients (59%) developed BRONJ after tooth extraction, whereas 7 (41%) developed it spontaneously (missing data for 1 patient). The mean number of BP infusions (38.1 ± 19.06 infusions vs. 10.5 ± 12.81 infusions; P<0.001) and duration of BP treatment (44.3 ± 24.34 mo vs. 14.6 ± 18.09 mo; P<0.001) were significantly higher in patients with BRONJ compared with patients without BRONJ. Multivariate Cox proportional hazards regression analysis showed that diabetes [hazard ratio (HR)=3.40; 95% confidence interval (CI), 1.14-10.11; P=0.028], hypothyroidism (HR=3.59; 95% CI, 1.31-9.83; P=0.013), smoking (HR=3.44; 95% CI, 1.28-9.26; P=0.015), and higher number of zoledronate infusions (HR=1.07; 95% CI, 1.03-1.11; P=0.001) significantly increased the risk of developing BRONJ.
  
  
  CONCLUSIONS
  Increased cumulative doses and long-term BP treatment are the most important risk factors for BRONJ development. Type of BP, diabetes, hypothyroidism, smoking, and prior dental extractions may play a role in BRONJ development.
authors.affiliation: Division of Periodontology, University of Minnesota School of Dentistry, Minneapolis, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Thumbigere-Math
authors.forename: Lam
authors.initials: L
authors.lastname: Tu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Huckabay
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Scott
authors.initials: S
authors.lastname: Lunos
authors.forename: David L
authors.initials: DL
authors.lastname: Basi
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hughes
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Leach
authors.forename: Karen K
authors.initials: KK
authors.lastname: Swenson
authors.forename: Rajaram
authors.initials: R
authors.lastname: Gopalakrishnan
mesh_terms: D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D015994:Incidence; D007275:Injections, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy*; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D000077268:Pamidronate; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate