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

Bone loss resulting from immobilization or disuse has been shown in hu mans 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 w ere fitted with specially designed mesh jackets. These jackets were us ed to bind the left forelimb against the body of the dog, thereby prev enting weight bearing on that limb. The experimental group (n=6) was t reated 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 s ame pattern, but received only saline injections. At the end of the ex periment, the dogs were sacrificed and the humeri and radii cleaned of soft tissues. Mineralization profiles, which determine the distributi on of mineralization densities of the cortical and trabecular bone wer e obtained and the main fractions were analyzed chemically. Static his tomorphometric parameters were determined on 5 mu m undecalcified sect ions from the distal humerus and on 50 mu m section of the humeral sha ft. Three point bending and torsional testing were performed on the ra dius. Immobilization induces hypomineralization in cortical and cancel lous bone but is prevented by APD treatment in cancellous. Immobilizat ion in this model induces osteopenia and increases turnover in cancell ous bone. These effects are counteracted by APD. Finally, cortical bon e density and stiffness are reduced by immobilization but this is prev ented by APD treatment. This experiment shows that the mature dog mode l is useful to study the immobilization-induced increase of bone turno ver and concomitant decrease in bone density, stiffness and mineraliza tion. It also shows that these effects of immobilization can be preven ted by treatment with the bisphosphonate pamidronate.