Mucoperiosteal flaps are used to access bone and root surfaces for debridement, pocket elimination, management of periodontal defects, and in regenerative procedures, as well as in implant surgery. Many reports show that periodontal surgery stimulates osteoclast activity with varying amounts of alveolar bone loss. Alendronate given intravenously significantly reduced alveolar bone loss in mucoperiosteal flap procedures. In the present study, we explored the effectiveness of different concentrations of alendronate, delivered at the surgical site at the time of surgery, in distant delivery in reducing alveolar bone loss. Following elevation of a mucoperiosteal flap next to molars of the rat mandible, a gelatin sponge soaked with different concentrations of alendronate (0, 1, 5, 20, or 40 mg/ml; experiment A) was applied to exposed bone on the experimental side. In the second group (experiment B), alendronate (0, 50, 200, or 400 microg) was topically delivered in the cheek submucosa on the left side (distant to the surgical site) in a small cut into which the gelatin sponge soaked with the drug was placed. Topical application of 200 microg and 400 microg doses of alendronate at the time of surgery was significantly effective (P <0.001) in reducing bone loss. Generally, the percentage of sections with mild bone loss (V1, V2) increased with an increase in the dose of alendronate, while the percentage of sections with severe bone loss (H1, H2) decreased with an increase in alendronate dose. Topical application of 400 microg of alendronate had a systemic effect. This study implies that topical delivery of alendronate at the time of surgery reduces bone loss in periodontal procedures involving mucoperiosteal flap surgery. The most effective dose is 200 microg for topical delivery at the surgical site and 400 microg for distant sites.