Animal studies were done using an in vivo dogmodel to examine the possible mechanism for theesophageal adverse events reported with alendronatesodium tablets. These studies showed that under low pHconditions alendronate sodium can cause esophagealirritation. No esophageal irritation occurred at pH 3.5or higher where the drug exists primarily as the sodiumsalt. The animal studies also showed that alendronate sodium can exacerbate preexisting esophagealdamage. Exposure of the esophageal mucosa for aprolonged period to alendronate sodium tablet can alsocause mild esophageal irritation. These findings suggest that the esophageal irritation in patientstaking Fosamax can be from prolonged contact with thetablet, reflux of acidic gastric contents withalendronate sodium, and exacerbation of preexistingesophageal damage. The findings also suggest that otherbisphosphonates can cause esophageal injury undersimilar conditions.