Comparative study of potential for bisphosphonates to damage gastric mucosa of rats

Bisphosphonates have generally few clinical adverse effects, the most common being gastrointestinal disturbances. It is generally believed that bisphosphonates with a primary amine are more irritating to the gastrointestinal tract than those without a primary amine. The objective of this study was to compare the gastric irritation potential of an amino bisphosphonate (alendronate) to that of two nonamino bisphosphonates (risedronate and etidronate) in a rat model at pharmacologically equivalent and clinically relevant doses. The doses used were 1, 5, 10, and 30 mg/kg/day for alendronate and risedronate and 40, 200, 400, and 1200 mg/kg/day for etidronate. These doses represent 5-150 times the recommended clinical dose. The drugs were given orally, daily by gavage for four weeks. The gastric irritation potential was assessed by gross and microscopic evaluation of multiple sections of the stomach. This study showed that, at pharmacologically equivalent doses, the gastric irritation potential for alendronate is no greater than that for etidronate or risedronate.