THE AMINOBISPHOSPHONATE ALENDRONATE INHIBITS BONE LOSS INDUCED BY THYROID-HORMONE IN THE RAT COMPARISON BETWEEN EFFECTS ON TIBIAE AND VERTEBRAE

The aims of this study were to develop a rat model of hyperthyroidism and to determine the efficacy of alendronate in the prevention of thyr oid hormone-induced bone loss. Ten week-old Sprague-Dawley rats inject ed with thyroxine 250 mug/kg/day (+T4) or vehicle (-T4) were treated w ith alendronate (+ALN) or vehicle (-ALN) orally 0.5 mg/kg/day. After 3 weeks of treatment histomorphometric parameters of cancellous bone re modeling were assessed in the proximal tibia and in the first lumbar v ertebra. In the secondary spongiosa of the tibia T4 treatment caused s ignificant bone loss, associated with increased bone turnover; trabecu lar bone volume, trabecular thickness and trabecular number were signi ficantly decreased. Osteoid and osteoclast surfaces increased in +T4/- ALN as compared to control. Alendronate prevented the increase in bone turnover and increased bone volume above control values without inter fering with the recruitment of osteoclasts. These changes were not app arent in the vertebra. It is concluded that excess thyroid hormone in the rat induces high turnover bone loss in the tibia which can be prev ented by alendronate through an inhibition of osteoclastic activity. T he lack of effects of thyroid hormone on the vertebra may be ascribed to a lower rate of basal bone turnover at that site.