Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone.

Abstract

The role of resorption in the anabolic response of bone to parathyroid hormone (PTH) is not well understood. In contrast to the increase in bone mass induced by intermittent PTH in intact rats, continuous infusion of PTH into thyroparathyroidectomized (TPTX) rats failed to increase bone volume. The objective of this study were to determine if continuous infusions of low doses of PTH were anabolic in intact rats and if inhibition of resorption would enhance or block an anabolic action of PTH. Young male rats were treated with either continuous infusion or intermittent injections of hPTH-(1-34) for 12 days. In experiment 1, PTH, infused daily at 4 micrograms per 100 g, increased femur calcium and dry weight. Unlike infusion of 8 micrograms PTH, which did not alter bone mass, intermittent PTH at 8 micrograms was anabolic and increased bone mass by increasing trabecular thickness and number. Infusion of 16 micrograms induced hypercalcemia and death. In experiment 2, lower dose daily infusions of 0.25-4 micrograms PTH per 100 g did not increase bone mass. In experiment 3, in rats pretreated with dichloromethylene diphosphonate (Cl2MDP) to inhibit resorption and subsequently exhibiting decreased bone formation, PTH, irrespective of the method of administration, reversed the inhibitory effects of Cl2MDP on bone formation. Thus, intermittent and continuous PTH increase bone formation independently of effects on bone resorption, but only intermittent PTH increases bone mass consistently.