Effects of Human Recombinant Calcitonin on a Rat Osteopenia Model Induced by TPTX and Arotinoid

Abstract

Recombinant human calcitonin (rh-CT) has been developed as an agent for patients with excessive bone resorption to replace calcitonins from animal species, which are associated with tolerance problems. In this study, inhibitory effects of rh-CT against bone resorption were examined in thyroparathyroidectomized (TPTX) rats, the animal model of accelerated bone resorption induced by administering a synthetic retinoid (arotinoid). The arotinoid-treated TPTX rats exhibited signs of stimulated bone resorption, such as hypercalcemia, reduced bone mineral density, and inferior bone strength. Significant improvements were seen in all of these changes after a daily treatment with rh-CT (30, 300 U/kg s.c.) for 1 week. A histomorphometrical analysis showed that the treatment with rh-CT markedly suppressed the reduction of trabecular bone volume and that of cortical thickness in the femur of arotinoid-treated TPTX rats. These results suggest that rh-CT may prevent osteopenia caused by accelerated bone resorption.

Action of Calciotropic Hormones on Bone Metabolism – Role of Vitamin D3 in Bone Remodeling Events

“…In vivo calcium metabolism and bone remodeling studies can be difficult to interpret because of the network of mineral and hormonal interactions that are involved. Rats that have undergone surgical removal of the thyroid and parathyroid glands are useful for investigational research in studying the pathophysiology of human hypoparathyroidism, hypothyroidism, calcium and phosphate homeostasis and bone metabolism and particularly for evaluation of compounds with the potential to inhibit bone resorption or elicit bone formation [27][28][29][30][31][32][33][34][35][36] . We explored the utility of the TPTx rat with carefully controlled dietary vitamin D 3 and calcium as an in vivo model that allows investigation into the action of vitamin D 3 on bone remodeling events in total absence of PTH and CT. We also investigated and compared the action of vitamin D 3 on bone remodeling in a more clinically relevant, intact rat model.…”