Primary amino-bisphosphonates: a new class of gastrotoxic drugs--comparison of alendronate and aspirin.

BACKGROUND

Alendronate and pamidronate are primary amino-bisphosphonates used in the treatment of metabolic bone disease. Both drugs have been associated with reversible erosive esophagitis and as a result pamidronate 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-controlled, endoscopic comparison of alendronate (40 mg/day), aspirin (1, 300 mg/day), and placebo to evaluate the presence and degree of mucosal damage to the esophagus, stomach, and duodenal bulb.

RESULTS

Twelve normal healthy volunteers were studied both before and after 4 days of drug therapy. Placebo caused no visible endoscopic damage. In contrast, both aspirin and alendronate were associated with visible gastric mucosal injury in the majority of those studied (75 and 58%, respectively) and both were significantly greater than placebo (p < 0.001). The gastric mucosal injury was deemed severe in 50% of those receiving alendronate or aspirin; one alendronate-associated gastric ulcer was seen. Esophageal and duodenal bulb injury was seen once each, and both were associated with alendronate.

CONCLUSIONS

The primary amino-bisphosphonate alendronate causes mucosal injury to the upper gastrointestinal tract similar to aspirin. Even when used according to manufacturer's dosing instructions alendronate should probably be used with caution.