title: Gastric and duodenal safety of daily alendronate.
abstract: BACKGROUND
  Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use.
  
  
  METHODS
  Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review.
  
  
  RESULTS
  Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2).
  
  
  CONCLUSIONS
  Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Donahue
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
authors.forename: Susan E
authors.initials: SE
authors.lastname: Andrade
authors.forename: Arne
authors.initials: A
authors.lastname: Beck
authors.forename: Myde
authors.initials: M
authors.lastname: Boles
authors.forename: Diana S M
authors.initials: DS
authors.lastname: Buist
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Julie M
authors.initials: JM
authors.lastname: Chandler
authors.forename: Gary A
authors.initials: GA
authors.lastname: Chase
authors.forename: Bruce
authors.initials: B
authors.lastname: Ettinger
authors.forename: Paul
authors.initials: P
authors.lastname: Fishman
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.forename: Harry A
authors.initials: HA
authors.lastname: Guess
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Gurwitz
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: T R
authors.initials: TR
authors.lastname: Levin
authors.forename: Richard
authors.initials: R
authors.lastname: Platt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D004378:Duodenal Diseases / Q000139:chemically induced*; D004381:Duodenal Ulcer / Q000139:chemically induced*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006760:Hospitalization; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D013276:Stomach Ulcer / Q000139:chemically induced*
chemical_list: D019386:Alendronate