THE EFFECTS OF THE AMINOBISPHOSPHONATE ALENDRONATE ON THYROID HORMONE-INDUCED OSTEOPENIA IN RATS

Hyperthyroidism, either endogenous or iatrogenic, leads to increased b one turnover and osteopenia. This study was conducted to examine (1) w hether thyroid hormone excess in rats causes bone changes similar to t hose seen in patients with hyperthyroidism, and (2) the effects of the aminobisphosphonate alendronate on the thyroid hormone-induced bone c hanges. Sprague-Dawley male rats, divided into four groups, received L -thyroxine (T4) 250 mug/kg/day (+T4) or vehicle (-T4) subcutaneously s ix times per week and alendronate 1.75 mg/kg (+ALN) or vehicle (-ALN) orally twice a week. Rats were sacrificed after 3 weeks of treatment, blood samples were analyzed for serum T4, triiodo-L-thyronine (T3), an d osteocalcin, and the proximal tibiae were processed for histomorphom etric analysis. Serum T4 and T3 levels measured 20-24 hours after the last injection were 2 to 2.5-fold higher in +T4 groups than in -T4 gro ups. Serum osteocalcin was significantly (P < 0.05) higher in +T4/-ALN group than in the other groups, which were not statistically differen t from each other. T4 treatment (+T4/-ALN) significantly decreased the amount of cancellous bone volume (-45%) and increased osteoid surface (+254%), osteoblast surface (+111%), and osteoclast surface (+176%) r elative to control values. Alendronate increased the bone volume above control values in both T4-treated (+T4/+ALN) and untreated (-T4/+ALN) rats, and prevented the T4-induced increase in bone turnover in +T4/ALN rats. It is concluded that (1) excess thyroid hormone induces canc ellous bone loss associated with high bone turnover in the rat, and (2 ) this bone loss can be prevented by alendronate through the inhibitio n of osteoclastic activity.