EFFECTS OF PREDNISOLONE AND DEFLAZACORT ON OSTEOCALCIN METABOLISM IN SHEEP

Glucocorticoids adversely affect bone and mineral metabolism through a number of mechanisms, including inhibition of bone formation. Deflaza cort is a glucocorticoid which has been reported to be relatively ''bo ne-sparing.'' We compared the effects in oophorectomized sheep of defl azacort and prednisolone on the metabolism of osteocalcin (OC), a mark er of osteoblast function. An [I-125]OC infusion method was used to me asure the OC plasma clearance rate (PCR) and OC plasma production rate (PPR). Six-day intravenous infusion of deflazacort and prednisolone ( in the dose range 0.007-1.00 mg/hour) induced dose-dependent decreases in OC PPR which were of a similar pattern but significantly different magnitude (P < 0.02); deflazacort demonstrated a potency about 150% t hat of prednisolone. Both steroids decreased plasma OC levels on a dos e-related basis but at the lower doses 0.05 mg/hour (P < 0.05) and 0.0 13 mg/hour (P < 0.0005), deflazacort caused greater decrements. OC PCR was significantly increased only by higher doses of deflazacort (1.00 mg/hour, 0.25 mg/hour; P < 0.05). Deflazacort and prednisolone increa sed both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects. We conclu de that plasma OC levels and OC PPR in sheep were more sensitive to th e effects of deflazacort than to prednisolone. At high doses, the depr essive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone tr eatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium. These findings indicate that prednisolone had simi larly potent effects on both bone and glucose metabolism while deflaza cort exhibited differential potency on the two systems. The greater po tency of deflazacort on bone in sheep may be due to species difference s in steroid metabolism or steroid-receptor interaction.