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American Journal of Pathology, Vol 102, 438-446, Copyright © 1981 by American Society for Investigative Pathology

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Effects of thyroxine on cortical bone remodeling in adult dogs: a histomorphometric study

WB High, CC Capen and HE Black

The effects of thyroxine on cortical bone remodeling were studied under conditions of normal and accelerated remodeling induced by surgical elevation of the periosteum. Six adult female beagle dogs were administered orally 1.0 mg of L-thyroxine per kg body weight daily for 60 days. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4-bis-N,N'-dicarboxymethyl aminomethyl fluorescein) in vivo double labeling of rib specimens taken before treatment and after 60 days. Thyroxine administered in moderate pharmacologic doses increased the activation frequency, number of bone-forming and -resorbing sites, and the osteoid seam circumference in unaltered bone. Thyroxine, by activating skeletal remodeling, increased bone turnover and both formation and resorption at the tissue level. In ribs with periosteal elevation and accelerated remodeling, thyroxine increased the activation frequency, number of bone resorption and formation sites, and ratio of bone resorptive-to-formative surfaces. In addition, thyroxine under these conditions resulted in an increase in the osteoid seam circumference, radial closure rate, and bone formation rate at the tissue level but decreased the osteon formation time. Under conditions of accelerated remodeling, thyroxine increased osteoblastic and resorptive activity to a greater degree than in unaltered bone and resulted in bone changes similar to that described in human beings with thyrotoxicosis. The increased serum calcium and phosphorus levels and urinary hydroxyproline excretion at several intervals during thyroxine administration were consistent with the morphometric evidence of increased bone turnover and resorption. These findings suggest that thyroxine is a potent activator of skeletal remodeling under conditions of both normal and accelerated remodeling.