 |
|
Upper Gastrointestinal Tract Safety Profile of Alendronate
The Fracture Intervention Trial
Douglas C. Bauer, MD;
Dennis Black, PhD;
Kristine Ensrud, MD;
Desmond Thompson, PhD;
Marc Hochberg, MD;
Michael Nevitt, PhD;
Thomas Musliner, MD;
Debra Freedholm, BSN, MBA;
for the Fracture Intervention Trial Research Group
Arch Intern Med. 2000;160:517-525.
Objectives To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)—particularly those of the stomach, duodenum, or esophagus—in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes.
Design Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d.
Participants A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded.
Measurements Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups—gastroduodenal and esophageal—to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes.
Results The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged  75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs).
Conclusion In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.
From the Division of General Internal Medicine (Dr Bauer) and the Department of Epidemiology and Biostatistics (Drs Bauer, Black, and Nevitt), University of California, San Francisco; the Division of Epidemiology, University of Minnesota, and the Section of General Internal Medicine, Veterans Affairs Medical Center, Minneapolis (Dr Ensrud); Merck and Co Inc, Rahway, NJ (Drs Thompson and Musliner and Ms Freedholm); and the Department of Medicine, University of Maryland, Baltimore (Dr Hochberg).
RELATED LETTER
Alendronate and Nonsteroidal Anti-inflammatory Drug Interaction Safety Is Not Established: A Reply
Douglas C. Bauer and for the Fracture Intervention Trial Research Group
Arch Intern Med. 2000;160(17):2686-2687.
EXTRACT
| FULL TEXT
RELATED ARTICLE
Archives of Internal Medicine Reader's Choice: Continuing Medical Education
Arch Intern Med. 2000;160(4):555-556.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Recognizing and Treating Glucocorticoid-Induced Osteoporosis in Patients With Pulmonary Diseases
Gluck and Colice
Chest 2004;125:1859-1876.
ABSTRACT
| FULL TEXT
Physiological and morphological effects of alendronate on rabbit esophageal epithelium
Dobrucali et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2002;283:G576-G586.
ABSTRACT
| FULL TEXT
Gastric and Duodenal Safety of Daily Alendronate
Donahue et al.
Arch Intern Med 2002;162:936-942.
ABSTRACT
| FULL TEXT
Antiresorptive Treatment of Postmenopausal Osteoporosis: Comparison of Study Designs and Outcomes in Large Clinical Trials with Fracture as an Endpoint
Marcus et al.
Endocr. Rev. 2002;23:16-37.
ABSTRACT
| FULL TEXT
Alendronate and Naproxen Are Synergistic for Development of Gastric Ulcers
Graham and Malaty
Arch Intern Med 2001;161:107-110.
ABSTRACT
| FULL TEXT
Alendronate and Nonsteroidal Anti-inflammatory Drug Interaction Safety Is Not Established: A Reply
Bauer and for the Fracture Intervention Trial Research Group
Arch Intern Med 2000;160:2686-2687.
FULL TEXT
Alendronate reduced days of bed rest and limited activity in postmenopausal women with osteoporosis and existing fractures
Johnell
Evid. Based Med. 2000;5:119-119.
FULL TEXT
Alendronate and Nonsteroidal Anti-inflammatory Drug Interaction Safety Is Not Established
Rothschild
Arch Intern Med 2000;160:1702-1702.
FULL TEXT
|
