GLUCOCORTICOID-INDUCED INHIBITION OF OSTEOBLASTIC BONE-FORMATION IN EWES - A BIOCHEMICAL AND HISTOMORPHOMETRIC STUDY

The mechanisms underlying glucocorticoid-induced osteoporosis in humans are a defect in bone formation associated with increased bone resorption. The latter may be due to elevated parathyroid hormone (PTH) levels induced by the impairment of intestinal calcium absorption caused by corticosteroids. In this study we analysed the effects of corticosteroids in old ewes, a potential model for the study of human bone turnover. Two groups of seven 9-year-old female sheep were selected. The first group was injected intramuscularly with a daily dose of 30 mg methylprednisone (MP) during the first 2 months and 15 mg during the last month. After 2 and 3 months of treatment, blood samples were taken. At the end of the experiment the animals were slaughtered and the iliac crest kept for bone histomorphometry. Serum osteocalcin (sOC) rapidly and markedly decreased in the MP-treated group compared with controls (-77%; p < 0.01). In contrast, at the end of the experiment serum calcium and PTH levels were similar in both groups. Histomorphometric analysis showed a significant reduction in the wall width of trabecular packets. Dynamic parameters reflecting bone formation at the tissue and cell levels were significantly lower in the MP-treated group than in controls, with a highly significant decrease in the mineralization rate (MAR: -63%, p < 0.05) and double-labeled perimeter (dLPm/B.Pm: -92% p < 0.05). The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period. Significant correlations were found between sOC and MAR, dLPm/B.Pm and BFR/B.Pm (with r' respectively 0.67, 0.76 and 0.51). In conclusion, the effects of corticosteroid on ewe bone remodeling are essentially characterized by a major bone formation defect without evidence of secondary hyperparathyroidism, although this cannot be totally excluded by our results. Ewes treated with glucocorticoids could represent a good model for evaluating the effects of drugs candidates for all bone conditions characterized by reduced bone formation resulting from osteoblastic depression.