Resorption is not essential for the stimulation of bone growth by hPTH-(1-34) in rats in vivo

Abstract

Chronic low doses of hPTH-(1-34) stimulate bone growth in rats in vivo. The objective of these studies was to determine if the anabolic effect of hPTH-(1-34) on rat bone in vivo is dependent on an initial stimulation of resorption by blocking resorption with either salmon calcitonin (CT) or dichloromethylene diphosphonate (Cl2MDP). Male Sprague-Dawley rats, 70-100 g, were treated with daily subcutaneous (SC) injections of vehicle (V) or hPTH-(1-34), 8 micrograms per 100 g (PTH), for 12 days. In experiment 1, rats were given CT for 3 (CT3) or 12 (CT12) days, either alone or in combination with hPTH-(1-34) (CT3-PTH and CT12-PTH) or vehicle for 12 days. In experiment 2, rats were pretreated for 4 days with Cl2MDP or its vehicle before starting the daily PTH or vehicle injections. Rats were then killed. Sera, femora, tibiae, and kidneys were removed for chemical and histomorphometric analyses. PTH, PTH-CT3, and PTH-CT12 rats showed significant increases in total bone calcium (18-23%), dry weight (DW, 13-25%), and bone-forming surfaces compared with their respective controls. Eroded (resorption) surfaces were comparable between the groups. Although weight gain and serum calcium were normal in rats treated for 3 days with CT, rats treated for 12 days with CT gained 14% less weight than controls and were hypophosphatemic, with reduced serum calcium and urea nitrogen. Total bone mass increased both in Cl2MDP rats (Ca 21%, DW 2%), where resorption was presumably blocked, and in PTH rats (Ca 31%, DW 19%). The increase in bone mass was greater in PTH-Cl2MDP rats (Ca 48%, DW 29%) than in rats treated with Cl2MDP alone, suggesting that although Cl2MDP blocked resorption, the anabolic response to PTH was not altered. As neither short-term treatment with CT nor Cl2MDP blocked the anabolic response of bone to hPTH-(1-34), this response does not appear to depend on the early stimulation of resorption.