A RAT MODEL OF THYROID HORMONE-INDUCED BONE LOSS - EFFECT OF ANTIRESORPTIVE AGENTS ON REGIONAL BONE-DENSITY AND OSTEOCALCIN GENE-EXPRESSION

Thyroid hormone has been shown to stimulate bone resorption. Both endo genous hyperthyroidism and exogenous thyroxine suppressive therapy hav e been associated with reduction in bone mineral density (BMD), but th e patholophysiology of thyroxine-induced bone loss is not well underst ood. First we studied the effect of L-T-4 (0.1-0.3 mu g/g body weight ip/day) on bone turnover in rats by measuring regional BMDs and osteoc alcin mRNA. Next we determined whether antiresorptive agents (calciton in 1 mu U/g ip/day or sodium etidronate given cyclically at 10 mu g/g po for 3 consecutive days out of every week) could prevent bone loss. Groups of 10 male Sprague-Dawley rats each weighing 320-350 g were stu died before and after 3 weeks of treatment. L-T-4 treatment resulted i n reduction in BMDs in the lumbar spine, tail, and femur as measured b y dual energy X-ray absorptiometry, but there was no correlation with the dosage of L-T-4 or the serum T-4 level. Treatment with sodium etid ronate or calcitonin alone did not alter the regional BMD. Cyclical so dium etidronate, but not calcitonin, was able to prevent the bone loss induced by L-T-4 treatment. L-T-4 caused a dose-dependent increase in femur osteocalcin mRNA concentration. Treatment with calcitonin resul ted in 50% reduction of osteocalcin mRNA, but sodium etidronate had no effect. Ire conclusion, cyclical sodium etidronate prevents bone loss induced by exogenous L-T-4 in rats and may be useful in preventing os teoporosis in patients given long term TSH-suppressive doses of thyrox ine therapy.