Background: Bisphosphonates are effective treatments for osteoporosis. Since some primary amino bisphosphonates are associated with oesophageal injury, we conducted a study of the upper gastrointestinal effects of risedronate, a pyridinyl bisphosphonate. Methods: Healthy, postmenopausal women received risedronate 5 mg (n=26), aspirin 2600 mg (n=27), or placebo (n=27) daily for 14 days and underwent endoscopy at baseline, Day 8 and Day 15. Results: Oesophageal erosions were noted in one subject in the aspirin group, two in the placebo group, and none in the risedronate group, and an ulcer in one aspirin‐treated subject. Gastric erosions and ulcers were observed most frequently in the aspirin group. Gastric ulcers were noted in eight subjects in the aspirin group, one in the placebo group, and none in the risedronate group (P=0.010, placebo vs. aspirin; P=0.002, risedronate vs. aspirin). Duodenal erosions and ulcers were observed in the aspirin group only. Gastroduodenal erosion scores of three or more occurred more frequently in the aspirin than in the risedronate and placebo groups (P < 0.001). Conclusions: Risedronate 5 mg was not associated with oesophageal or gastroduodenal ulcers in healthy, postmenopausal women, a population representative of patients who will receive risedronate in the clinical setting.

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