Glucocorticoids modify osteoblastic cell differentiation, number, and function. Glucocorticoids stimulate osteoclastogenesis and increase the expression of receptor activator of Nuclear factor-κB ligand and colony-stimulating factor-1, and decrease the expression of osteoprotegerin. However, the most significant effect of glucocorticoids in bone is an inhibition of bone formation. This inhibition is caused by a decrease in the number of osteoblasts secondary to a shift in the differentiation of mesenchymal cells away from the osteoblastic lineage, and an increase in the death of mature osteoblasts. Glucocorticoids decrease the function of the remaining osteoblasts directly and indirectly through the inhibition of insulin-like growth factor I expression. The stimulation of bone resorption is likely responsible for the initial bone loss after glucocorticoid exposure. Eventually, the inhibition of bone formation will cause a decrease in bone remodeling and a continued increased risk of fractures.
Abbreviations:11β-HSD 11β-hydroxysteroid dehydrogenase, C/EBP CCAAT/enhancer binding protein, IGF insulin-like growth factor, IGFBP Insulin-like growth factor binding protein, RANK-L receptor activator of NF-kB ligand
Glucocorticoids have important actions on skeletal tissue that eventually lead to the development of osteoporosis [1]. Significant bone loss occurs after the initial exposure to glucocorticoids, and even modest doses of glucocorticoids, frequently considered to be in the physiologic range, increase the risk of fractures [2•]. Histomorphometric analysis of bone biopsies from patients receiving glucocorticoids reveals increased bone resorption and decreased bone formation [3,4]. However, it is important to note that patients taking glucocorticoids often have an underlying inflammatory disease that causes bone resorption. Recent research has provided new insights into the mechanisms of glucocorticoid action at the cellular and molecular level, and the actions of these steroids on cells of the osteoblast and osteoclast lineages, either directly or through the regulation of bone growth factors.