Glucocorticoids and bone: local effects and systemic implications

• Endogenous glucocorticoids are required for normal bone development and bone cell function.
• Excess glucocorticoids are detrimental to bone structure and strength through their negative effects on osteoblast and osteocyte function.
• Osteoanabolic agents may prove superior to bisphosphonates in the treatment of glucocorticoid-induced osteoporosis.
• The suppression of osteoblast function and osteocalcin synthesis plays an important role in glucocorticoid-induced diabetes and obesity.

Glucocorticoids (GCs) are highly effective in the treatment of inflammatory and autoimmune conditions but their therapeutic use is limited by numerous adverse effects. Recent insights into the mechanisms of action of both endogenous and exogenous GCs on bone cells have unlocked new approaches to the development of effective strategies for the prevention and treatment of GC-induced osteoporosis. Furthermore, topical studies in rodents indicate that the osteoblast-derived peptide, osteocalcin, plays a central role in the pathogenesis of GC-induced diabetes and obesity. These exciting findings mechanistically link the detrimental effects of GCs on bone and energy metabolism. In this article we review the physiology and pathophysiology of GC action on bone cells, and discuss current and emerging concepts regarding the molecular mechanisms underlying adverse effects of GCs such as osteoporosis and diabetes.