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 endogenous hyperthyroidism and exogenous thyroxine suppressive therapy have been associated with reduction in bone mineral density (BMD), but the patholophysiology of thyroxine-induced bone loss is not well understood. First we studied the effect of L-T4 (0.1-0.3 microgram/g body weight ip/day) on bone turnover in rats by measuring regional BMDs and osteocalcin mRNA. Next we determined whether antiresorptive agents (calcitonin 1 microU/gip/day or sodium etidronate given cyclically at 10 micrograms/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 studied before and after 3 weeks of treatment. L-T4 treatment resulted in reduction in BMDs in the lumbar spine, tail, and femur as measured by dual energy X-ray absorptiometry, but there was no correlation with the dosage of L-T4 or the serum T4 level. Treatment with sodium etidronate or calcitonin alone did not alter the regional BMD. Cyclical sodium etidronate, but not calcitonin, was able to prevent the bone loss induced by L-T4 treatment. L-T4 caused a dose-dependent increase in femur osteocalcin mRNA concentration. Treatment with calcitonin resulted in 50% reduction of osteocalcin mRNA, but sodium etidronate had no effect. In conclusion, cyclical sodium etidronate prevents bone loss induced by exogenous L-T4 in rats and may be useful in preventing osteoporosis in patients given long term TSH-suppressive doses of thyroxine therapy.
Kung
A W
AW
Department of Medicine, Queen Mary Hospital, University of Hong Kong.
Ng
F
F
D000818:Animals; D001483:Base Sequence; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D002116:Calcitonin / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D012968:Etidronic Acid / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D015675:Osteocalcin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*
D018076:DNA, Complementary; D012333:RNA, Messenger; D015675:Osteocalcin; D002116:Calcitonin; D012968:Etidronic Acid; D013974:Thyroxine