ALENDRONATE INDUCES GASTRIC INJURY AND DELAYS ULCER HEALING IN RODENTS

Gastric ulceration associated with the use of NSAIDs is most frequentl y observed in elderly women, the same sector of society most likely to be receiving therapy for osteoporosis. As some anti-osteoporosis medi cations have been suggested to irritate the upper gastrointestinal muc osa, we evaluated the ability of one such drug, alendronate, to damage the gastric mucosa and to influence the severity and healing of gastr ic ulcers in rodents. The effects of alendronate on indomethacin-induc ed antral ulceration was evaluated in the rabbit, while effects on ulc er healing and on the formation of gastric erosions was evaluated in t he rat. Effects of alendronate on gastric acid secretion, blood flow a nd prostaglandin synthesis were also evaluated. Alendronate caused ero sions in the rabbit stomach, but not antral ulceration. However, at th e highest doses tested (80 mg) alendronate increased the incidence and size of indomethacin-induced antral ulcers. Alendronate also enhanced indomethacin-induced gastric damage in the rat, and delayed gastric u lcer healing. These effects of alendronate were not attributable to ch anges in gastric acid secretion, blood flow, prostaglandin synthesis o r the pharmacokinetics of indomethacin. The damaging effects of alendr onate on the stomach were due to topical irritant effects and could be observed at concentrations as low as 4 mg/ml within 30 min of oral ad ministration or topical superfusion. These results support preliminary clinical evidence. that alendronate can damage the gastric mucosa. Wh ile gastric injury may be a rare occurrence in patients taking this dr ug, concomitant use of alendronate and NSAIDs may increase the inciden ce or severity of ulceration.