THE EFFECT OF PAMIDRONATE IN A NEW MODEL OF IMMOBILIZATION IN THE DOG

Bone loss resulting from immobilization or disuse has been shown in humans following paralysis or bedrest. We have developed a new model of immobilization in the dog which is reversible and we have studied the effect of pamidronate (APD) in this model. Twelve mature beagle dogs were fitted with specially designed mesh jackets. These jackets were used to bind the left forelimb against the body of the dog, thereby preventing weight bearing on that limb. The experimental group (n=6) was treated with an I.V. dose of 0.45 mu mol/kg/day APD (pamidronate) for 7 days followed by 3 weeks without treatment. This cycle was repeated 3 times for a total of 12 weeks. The control group (n=6) followed the same pattern, but received only saline injections. At the end of the experiment, the dogs were sacrificed and the humeri and radii cleaned of soft tissues. Mineralization profiles, which determine the distribution of mineralization densities of the cortical and trabecular bone were obtained and the main fractions were analyzed chemically. Static histomorphometric parameters were determined on 5 mu m undecalcified sections from the distal humerus and on 50 mu m section of the humeral shaft. Three point bending and torsional testing were performed on the radius. Immobilization induces hypomineralization in cortical and cancellous bone but is prevented by APD treatment in cancellous. Immobilization in this model induces osteopenia and increases turnover in cancellous bone. These effects are counteracted by APD. Finally, cortical bone density and stiffness are reduced by immobilization but this is prevented by APD treatment. This experiment shows that the mature dog model is useful to study the immobilization-induced increase of bone turnover and concomitant decrease in bone density, stiffness and mineralization. It also shows that these effects of immobilization can be prevented by treatment with the bisphosphonate pamidronate.