EFFECT OF ALENDRONATE ON FRACTURE-HEALING AND BONE REMODELING IN DOGS

To examine the effect of alendronate (4-amino-1-hydroxybutylidene bisp hosphonate) on fracture repair, the drug was given to mature beagle do gs orogastrically at 2 mg/kg/day for 9 weeks preceding fracture, 16 we eks after fracture, or both before and after fracture (25 weeks). A tr ansverse mid-diaphyseal fracture of the right radius was surgically in duced and was stabilized by external coaptation splinting. Fracture he aling and bone remodeling were evaluated by radiography, gross and his tological examination, and bone histomorphometry. The mechanical prope rties of the fracture callus were determined by a four-point bending t est. Radiographs and gross and microscopic examination demonstrated no rmal bone healing at the fracture site in all dogs. In dogs that recei ved alendronate during the fracture healing period, at 16 weeks the ca lluses were approximately 2-3 times larger than those in dogs that rec eived a placebo during the healing period. This is consistent with slo wer callus bone remodeling, an expected pharmacological effect of the compound. Bone histomorphometry demonstrated that treatment with alend ronate did not inhibit bone formation or mineralization. Mechanical te sting showed that the ultimate load at failure and the flexural rigidi ty of both the fractured and contralateral intact bone were unaffected by treatment with alendronate. Therefore, in this study, treatment wi th alendronate before or during fracture healing, or both, resulted in no adverse effects on the union, strength, or mineralization of bone in mature beagle dogs.