Therapeutics and Drugs Brief
Are Bisphosphonates Really Toxic to the GI Tract?
Source: Lowe CE, et al. Am J Gastroenterol 2000;95:634-640.
Lowe and colleagues conducted a double-blind, randomized, placebo-controlled trial with 32 healthy female volunteers aged between 40 and 65 years. They were randomized to receive either placebo or alendronate 10 mg daily for one month. Endoscopic mucosal abnormalities in the esophagus, stomach, and duodenum were scored and compared using validated endoscopic grading systems before and after one month of treatment. Symptom scores were also evaluated, and small intestinal permeability assessed. Lowe et al found no difference in symptom or endoscopic scores for the esophagus, stomach, or duodenum before and after treatment with alendronate or between the alendronate and placebo groups. There were also no significant changes in mucosal permeability in the stomach or small intestine. Lowe et al conclude that alendronate does not cause predictable esophageal, gastric, or duodenal mucosal damage when used as directed.
Comment by Eamonn M.M. Quigley, MD
Bisphosphonates have assumed an important role in the management of osteoporosis, an increasingly common problem among the elderly female population. Initial reports suggested that their use was associated with significant upper gastrointestinal (GI) mucosal damage, especially involving the esophagus. However, large randomized controlled trials have failed to support these data. This carefully performed study suggests that, when the dose of alendronate is not excessively high, and when the drug is taken as directed (i.e., medication taken with a full glass of water and the patient remains upright for 30 minutes post-ingestion), its use is not associated with GI symptoms, endoscopic damage, mucosal pathology, or altered mucosal permeability. While these findings are reassuring, it must be conceded that they do not rule out the possibility of mucosal injury in particularly susceptible individuals or with higher doses.
1. de Groen PC, et al. N Engl J Med 1996;335:1016-1021.
2. Lanza F, et al. Am J Gastroenterol 1998;93:753-757.
Dr. Quigley is Professor, Department of Medicine, National University of Ireland, Cork, Ireland.
The use of alendronate is not associated with esophageal, gastric, or duodenal mucosal damage when:
a. the dose is not excessively high.
b. it is taken as directed.
c. Neither a or b
d. Both a and b