A mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday.

摘要: Glucocorticoid-induced osteonecrosis is a common and dose-limiting adverse event. The goal of this study was to establish mouse model glucocorticoid-induced suitable for testing the effects different treatment strategies on its frequency. Fourteen murine strains were screened using various glucocorticoids, routes administration, diets. Four-week old male BALB/cJ mice treated with oral dexamethasone up 12 weeks either by continuous dosing or discontinuous dosing, without asparaginase. Histopathological features distal femurs examined light microscopy. Osteonecrotic lesions characterized empty lacunae osteocyte ghosts in trabecular bone surrounded necrotic marrow edema. incidence induced 40%–45% (4/10 5/11) at weeks. frequency trended lower after compared (8% vs. 45%) (P = 0.06) despite comparable cumulative plasma exposure. Asparaginase hastened occurrence which observed as early 4 50% 6 A established. Discontinuous less osteonecrotic than treatment, consistent possible benefits “steroid holiday” seen clinical settings. Moreover, asparaginase osteonecrosis, indicating that drugs may interact glucocorticoids affect risk.