S-KETOPROFEN INHIBITS TENOTOMY-INDUCED BONE LOSS AND DYNAMICS IN WEANLING RATS

The objects of this study were to determine whether S-Ketoprofen, a no n-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats- Forty-five 4-week-old Sprague-Dawley female rats were either sham-operated or subjected to k nee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluo rescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancel lous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This wa s due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-keto profen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resor ption. In the tibial shaft, tenotomy inhibited the enlargement of tota l tissue area by depressing periosteal bone formation, and thus inhibi ted age-related cortical bone gain. S-ketoprofen treatment did not pre vent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose le vels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenoto my inhibited age-related bone gain and stimulated bone loss in cancell ous bone sites, and only inhibited age-related bone gain in cortical b one sites. S-ketoprofen treatment at the highest dose levels prevented the changes in cancellous bone, and reduced marrow area to increase c ortical bone in the tibial shafts.