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. Deflazacort is a glucocorticoid which has been reported to be relatively "bone-sparing." We compared the effects in oophorectomized sheep of deflazacort and prednisolone on the metabolism of osteocalcin (OC), a marker of osteoblast function. An [125]OC infusion method was used to measure 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% that of prednisolone. Both steroids decreased plasma OC levels on a dose-related basis but at the lower doses 0.05 mg/hour (P < 0.05) and 0.013 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 increased both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects. We conclude that plasma OC levels and OC PPR in sheep were more sensitive to the effects of deflazacort than to prednisolone. At high doses, the depressive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone treatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Connell
S L
SL
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia.
Tresham
J
J
Fortune
C L
CL
Farrugia
W
W
McDougall
J G
JG
Scoggins
B A
BA
Wark
J D
JD
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D008657:Metabolic Clearance Rate; D010006:Osteoblasts / Q000502:physiology; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism*; D010052:Ovariectomy; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007457:Iodine Radioisotopes; D011282:Pregnenediones; D015675:Osteocalcin; D011239:Prednisolone; C021988:deflazacort; D002118:Calcium