The CRH-Transgenic Cushingoid Mouse Is a Model of Glucocorticoid-Induced Osteoporosis

JBMR Plus. 2017 Jun 28;1(1):46-57. doi: 10.1002/jbm4.10009. eCollection 2017 Aug.


Glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive properties, which accounts for their widespread prescription and use. Unfortunately, a limitation to GC therapy is a wide range of negative side effects including Cushing's syndrome, a disease characterized by metabolic abnormalities including muscle wasting and osteoporosis. GC-induced osteoporosis occurs in 30% to 50% of patients on GC therapy and thus, represents an important area of study. Herein, we characterize the molecular and physiologic effects of GC-induced osteoporosis using the Cushing's mouse model, the corticotropin releasing hormone (CRH) transgenic mouse (CRH-Tg). The humeri, femurs, and tibias from wild-type (WT) and CRH-Tg male mice, aged 13 to 14 weeks old were subjected to multiple bone tests including, micro-computed tomography (μCT), static and dynamic histomorphometry, strength testing, and gene expression analyses. The CRH-Tg mice had a 38% decrease in cortical bone area, a 35% decrease in cortical thickness, a 16% decrease in trabecular thickness, a sixfold increase in bone adiposity, a 27% reduction in osteoid width, a 75% increase in bone-resorbing osteoclast number/bone surface, a 34% decrease in bone formation rate, and a 40% decrease in bone strength compared to WT mice. At the gene expression level, CRH-Tg bone showed significantly increased osteoclast markers and decreased osteoblast markers, whereas CRH-Tg muscle had increased muscle atrophy gene markers compared to WT mice. Overall, the CRH-Tg mouse model aged to 14 weeks recapitulated many features of osteoporosis in Cushing's syndrome and thus, represents a useful model to study GC-induced osteoporosis and interventions that target the effects of GCs on the skeleton. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.