OBJECTIVE:Alendronate is rapidly gaining widespread use in the treatment of osteoporosis. However, recent postmarketing surveys and endoscopic studies suggest that its use may be associated with significant predictable esophageal and gastric mucosal toxicity, similar to that of aspirin and nonsteroidal anti-inflammatory drugs. Because treatment of osteoporosis may be needed in as many as 30% of all postmenopausal women, and considering that alendronate could be used in all postmenopausal women as prevention, definition of potential mucosal toxicity is crucial. Our aim was to study the upper gastrointestinal toxicity of alendronate in an age-appropriate female population using a clinically applicable dose (10 mg/day) to determine whether it causes predictable damage in the proximal gastrointestinal mucosa in a fashion similar to that seen with aspirin and nonsteroidal anti-inflammatory drugs. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in 32 healthy female volunteers between the ages of 40 and 65 yr recruited by newspaper advertisement. Endoscopic mucosal abnormalities in the esophagus, stomach, and duodenum both before and after 1 month of treatment were scored and compared using validated endoscopic grading systems. Symptom scores before and after treatment were determined. Noninvasive measurements of gastrointestinal permeability were obtained before, during, and after treatment using sucrose and mannitol/lactulose urinary excretions. RESULTS:Endoscopic scores before and after treatment with alendronate were not significantly different. Similarly, mean symptom scores in the alendronate group did not change significantly after treatment. There were no significant mucosal permeability changes in the stomach or small intestine after treatment. CONCLUSION:Alendronate does not cause predictable esophageal, gastric, or duodenal mucosal damage when used as directed.
RCT Entities:
OBJECTIVE:Alendronate is rapidly gaining widespread use in the treatment of osteoporosis. However, recent postmarketing surveys and endoscopic studies suggest that its use may be associated with significant predictable esophageal and gastric mucosal toxicity, similar to that of aspirin and nonsteroidal anti-inflammatory drugs. Because treatment of osteoporosis may be needed in as many as 30% of all postmenopausal women, and considering that alendronate could be used in all postmenopausal women as prevention, definition of potential mucosal toxicity is crucial. Our aim was to study the upper gastrointestinal toxicity of alendronate in an age-appropriate female population using a clinically applicable dose (10 mg/day) to determine whether it causes predictable damage in the proximal gastrointestinal mucosa in a fashion similar to that seen with aspirin and nonsteroidal anti-inflammatory drugs. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in 32 healthy female volunteers between the ages of 40 and 65 yr recruited by newspaper advertisement. Endoscopic mucosal abnormalities in the esophagus, stomach, and duodenum both before and after 1 month of treatment were scored and compared using validated endoscopic grading systems. Symptom scores before and after treatment were determined. Noninvasive measurements of gastrointestinal permeability were obtained before, during, and after treatment using sucrose and mannitol/lactulose urinary excretions. RESULTS: Endoscopic scores before and after treatment with alendronate were not significantly different. Similarly, mean symptom scores in the alendronate group did not change significantly after treatment. There were no significant mucosal permeability changes in the stomach or small intestine after treatment. CONCLUSION:Alendronate does not cause predictable esophageal, gastric, or duodenal mucosal damage when used as directed.