SHORT-TERM EFFECTS OF CORTICOSTEROIDS ON TRABECULAR BONE REMODELING IN OLD EWES

This study was an attempt to develop an animal model of steroid-induce d low bone formation, potentially suitable for testing bone forming ag ents. The short-term effects of corticosteroids on bone remodeling wer e analyzed in ewes. One group of 16 animals (mean age: 9 +/- 1 Sears) received a daily intramuscular injection of 16 mg of methylprednisone (MP group) for 3 months, The other group of 16 animals was considered the control group, At the end of treatment, significant decreases of o steoblastic (-50%) and mineralizing (-64%) perimeters and wall width ( -5%) were noted in the MP group, The bone formation rate at the tissue level was significantly decreased by 91%, In contrast, at the cell le vel, there was no reduction in the daily production of matrix by the o steoblasts: Aj.AR was 30% lower than in controls, but the difference w as not significant. At the end of the treatment, a significant increas e in eroded perimeter (+97%) was associated with a significant decreas e of osteoclast number, Biochemical markers of bone formation (osteoca lcin and bone-specific alkaline phosphatase) and urinary cAMP were unc hanged. Due to the short duration of the treatment, neither bone volum e nor microarchitecture parameters were modified, The decreases of bot h the activation frequency and osteoclast number associated with the i ncrease in eroded surfaces suggest a prolongation of the reversal phas e due to an inhibition of osteoblast differentiation. Changes of bone formation in ewes induced by short-term administration of MP were simi lar to those reported after 3 months of treatment in humans, Thus, cor ticosteroid-treated ewes may represent a suitable animal model of low bone formation. (C) 1997 by Elsevier Science Inc.