Mechanisms of glucocorticoid action in bone.
Glucocorticoids cause profound effects on bone cell replication, differentiation, and function. Glucocorticoids increase bone resorption by stimulating osteoclastogenesis by increasing the expression of RANK ligand and decreasing the expression of its decoy receptor, osteoprotegerin. In accordance with the increase in bone resorption, glucocorticoids stimulate the expression of collagenase 3 by posttranscriptional mechanisms. The most significant effect of glucocorticoids in bone is an inhibition of bone formation. This is because of a decrease in the number of osteoblasts and their function. The decrease in cell number is secondary to a decrease in osteoblastic cell replication and differentiation, and an increase in the apoptosis of mature osteoblasts. Glucocorticoids decrease osteoblastic function directly and indirectly through the modulation of growth factor expression, receptor binding, or binding protein levels. Clinically, patients with glucocorticoid-induced osteoporosis (GIOP) develop bone loss in the first few months of glucocorticoid exposure, and modest doses of glucocorticoids increase the risk of fractures of the spine and hip. Bisphosphonates inhibit bone resorption and prevent and revert the bone loss that follows glucocorticoid exposure. Anabolic agents, such as parathyroid hormone, stimulate bone formation and can increase bone mass in GIOP.
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA. ecanalis@stfranciscare.org
Ernesto
E
Canalis
Anne M
AM
Delany
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D012377:Rodentia
D005938:Glucocorticoids; D006133:Growth Substances; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases