Parathyroid Hormone Stimulates the Bone Apposition Rate Independently of Its Resorptive Action: Differential Effects of Intermittent and Continuous Administration*

Abstract

The deposition of mineralized bone matrix by differentiated osteoblasts was studied in rats in vivo by labeling the bone with three doses of tetracycline given at 48-h intervals. Only bone formation loci bearing all three tetracycline doses were measured, thus eliminating sites where bone formation was not continuous during the labeling period. Using this technique, the effects of intact bovine parathyroid hormone [bPTH-(1-84)] and of a synthetic amino-terminal fragment of human PTH [hPTH-(1-34)] were measured in thyroparathyroidectomized animals. bPTH-(1-84), administered sc, and hPTH-(1-34), administered iv, caused a dose-dependent increase in the bone apposition. Subcutaneous administration of hPTH-(1-34) in doses varying from 2.7-173.0 pmol/rat.day had no effect, probably due to the degradation of the hormone when administered this way. We also compared the effects of bPTH-(1-84) when administered by either daily sc injections or continuous infusion. Continuous infusion of bPTH-(1-84) resulted in an increased apposition rate. Using a morphometric technique, we also found an increase in both formation and resorption surfaces and a net decrease in the trabecular bone volume in this group. Daily injection of the hormone caused an increase in the bone apposition rate, accompanied by an increase in the formation surface without an increase in the resorption surface. This resulted in a net increase in trabecular bone volume. The results thus suggest that the resorptive effects of bPTH-(1-84) can be separated from the effects of the hormone on the apposition rate.