Glucocorticoid-induced osteoporosis is caused by the inhibition of osteoblast differentiation and induction of osteoblast and osteocyte apoptosis. Glucocorticoids inhibit osteoblast differentiation by reducing the expression of Wnt signaling proteins, osteocalcin, and AP-1. Further, glucocorticoids induce osteoblast and osteocyte apoptosis by regulating the expression of Bcl-2 family proteins. Apoptotic signaling enhances osteoblast differentiation, at least in part, through FoxO. However, FoxO is also likely to be involved in the inhibition of osteoblast differentiation by glucocorticoids.