Short-term effects of corticosteroids on trabecular bone remodeling in old ewes.

This study was an attempt to develop an animal model of steroid-induced low bone formation, potentially suitable for testing bone forming agents. The short-term effects of corticosteroids on bone remodeling were analyzed in ewes. One group of 16 animals (mean age: 9 +/- 1 years) 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 osteoblastic (-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 level, there was no reduction in the daily production of matrix by the osteoblasts: Aj.AR was 40% lower than in controls, but the difference was not significant. At the end of the treatment, a significant increase in eroded perimeter (+97%) was associated with a significant decrease of osteoclast number. Biochemical markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) and urinary cAMP were unchanged. Due to the short duration of the treatment, neither bone volume nor microarchitecture parameters were modified. The decreases of both the activation frequency and osteoclast number associated with the increase in eroded surfaces suggest a prolongation of the reversal phase due to an inhibition of osteoblast differentiation. Changes of bone formation in ewes induced by short-term administration of MP were similar to those reported after 3 months of treatment in humans. Thus, corticosteroid-treated ewes may represent a suitable animal model of low bone formation.