PRIMARY AMINO-BISPHOSPHONATES - A NEW CLASS OF GASTROTOXIC DRUGS - COMPARISON OF ALENDRONATE AND ASPIRIN

Background: Alendronate and pamidronate are primary amino-bisphosphona tes used in the treatment of metabolic bone disease, Both drugs have b een associated with reversible erosive esophagitis and as a result pam idronate is approved in the United States only for parenteral use, In rats, alendronate causes acute gastric mucosal damage similar to that seen with aspirin or nonsteroidal anti-inflammatory drugs, Methods: We performed a blinded, crossover, randomized, single-center, placebo-co ntrolled, endoscopic comparison of alendronate (40 mg/day), aspirin (1 ,300 mg/day), and placebo to evaluate the presence and degree of mucos al damage to the esophagus, stomach, and duodenal bulb, Results: Twelv e normal healthy volunteers were studied both before and after 4 days of drug therapy, Placebo caused no visible endoscopic damage, In contr ast, both aspirin and alendronate were associated with visible gastric mucosal injury in the majority of those studied (75 and 58%, respecti vely) and both were significantly greater than placebo (p < 0.001), Th e gastric mucosal injury was deemed severe in 50% of those receiving a lendronate or aspirin; one alendronate-associated gastric ulcer was se en, Esophageal and duodenal bulb injury was seen once each, and both w ere associated with alendronate, Conclusions: The primary amino-bispho sphonate alendronate causes mucosal injury to the upper gastrointestin al tract similar to aspirin, Even when used according to manufacturer' s dosing instructions alendronate should probably be used with caution .