Mechanisms of glucocorticoid action in bone.

Glucocorticoids induce rapid bone loss and increase the risk for osteoporotic fractures. The mechanisms include a phase of increased bone resorption, probably a result of the increased expression of receptor activator of nuclear factor-k-B ligand and colony stimulating factor-1, followed-up by a decrease in bone formation. This effect is central to the actions of glucocorticoids in bone and it is secondary to the loss of bone forming cells, caused by an inhibition of cell differentiation and an increase in the apoptosis of mature osteoblasts and osteocytes. Glucocorticoids also inhibit the function of mature osteoblasts and suppress the synthesis of insulin-like growth factor-I, an agent that enhances bone formation. Glucocorticoids alter the growth hormone/insulin-like growth factor axis in cartilage and, as a consequence, suppress linear growth.