The treatment of periodontal disease has been largely directed at the microbiological etiology. The prevention of bone loss by modulating the host response to the bacteria may be a useful adjunctive method in the management of periodontitis. Alendronate, an amino bisphosphonate, may inhibit bone loss in osteolytic diseases by altering osteoclast activity. The objective of this double-blind study was to evaluate alendronate inhibition of alveolar bone loss in the naturally occurring beagle dog model of periodontitis. Sixteen 7 to 9 year old beagles with moderate-to-severe periodontitis were studied for 6 months. The dogs were stratified into two groups based on initial periodontal severity. One group received 3.0 mg/kg alendronate weekly orally and the other group received a placebo. Silk ligatures were placed on the study teeth for the first 3 months of the study to exacerbate the periodontal destruction. Clinical data were collected for attachment level, gingival index, plaque index, and mobility at baseline and one-month intervals. Intraoral radiographs were made at baseline and at 3 and 6 months. The mandibles were processed for histology at month 6. The radiographs were analyzed by digital image analysis of the subtracted images. A statistically significant difference in bone mass (P < 0.001) was observed between the alendronate and placebo groups. The bisphosphonate had no effect on the clinical parameters of gingival inflammation or plaque. A trend toward decreased attachment loss and mobility was observed in favor of the alendronate group.(ABSTRACT TRUNCATED AT 250 WORDS)