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Gastric and Duodenal Safety of Daily Alendronate
James G. Donahue, DVM, PhD;
K. Arnold Chan, MD, ScD;
Susan E. Andrade, ScD;
Arne Beck, PhD;
Myde Boles, PhD;
Diana S. M. Buist, PhD;
Vincent J. Carey, PhD;
Julie M. Chandler, PhD;
Gary A. Chase, PhD;
Bruce Ettinger, MD;
Paul Fishman, PhD;
Michael Goodman, PhD;
Harry A. Guess, MD, PhD;
Jerry H. Gurwitz, MD;
Andrea Z. LaCroix, PhD;
T. R. Levin, MD;
Richard Platt, MD, MS
Arch Intern Med. 2002;162:936-942.
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.
Participants and 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.
From the Channing Laboratory, Department of Medicine, Brigham and Women's
Hospital, and Harvard Medical School, Boston, Mass (Drs Donahue, Chan, Carey,
and Platt); Department of Epidemiology, Harvard School of Public Health, Boston,
Mass (Dr Chan); Meyers Primary Care Institute, Fallon Healthcare System, and
University of Massachusetts Medical School, Worcester (Drs Andrade and Gurwitz);
Kaiser Permanente Colorado, Denver (Dr Beck); Kaiser Permanente Northwest,
Portland, Ore (Dr Boles); Group Health Cooperative, Seattle, Wash (Drs Buist,
Fishman, and La Croix); Merck & Co, Inc, West Point, Pa (Drs Chandler
and Guess); Henry Ford Health System, Detroit, Mich (Dr Chase); Kaiser Permanente
Medical Care Program, Oakland, Calif (Drs Ettinger and Levin); HealthPartners
Research Foundation, Minneapolis, Minn (Dr Goodman); University of California,
San Francisco, School of Medicine (Dr Levin); and Department of Ambulatory
Care and Prevention, Harvard Medical School, and Harvard Pilgrim Health Care,
Boston, Mass (Dr Platt). Dr Ettinger received grant support from Eli Lilly,
Merck & Co, Solvay, Berlex, Proctor and Gamble, and Novogen and was a
paid consultant for Eli Lilly, Solvay, Berlex, Proctor and Gamble, and Durbied.
Dr Levin received research support from Novartis and Merck & Co. Drs Chandler
and Guess are employees and stockholders in Merck & Co.
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