Gastric and duodenal safety of daily alendronate.
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.
Donahue
James G
JG
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.
Chan
K Arnold
KA
Andrade
Susan E
SE
Beck
Arne
A
Boles
Myde
M
Buist
Diana S M
DS
Carey
Vincent J
VJ
Chandler
Julie M
JM
Chase
Gary A
GA
Ettinger
Bruce
B
Fishman
Paul
P
Goodman
Michael
M
Guess
Harry A
HA
Gurwitz
Jerry H
JH
LaCroix
Andrea Z
AZ
Levin
T R
TR
Platt
Richard
R
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*
D019386:Alendronate