11beta-Hydroxysteroid dehydrogenase: a regulator of glucocorticoid response in osteoporosis.

Until recently it was assumed that there was a direct relationship between the level of glucocorticoids in the circulation and the levels within tissue. The identification and characterisation of local glucocorticoid modifying enzymes in a range of tissues however demonstrated that tissue levels of glucocorticoids can be regulated independently of circulating levels. This appears to be the case in bone where the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes are expressed. Glucocorticoids are actively generated within osteoblasts by the 11beta-HSD1 enzyme and this generation increases with proinflammatory cytokines, glucocorticoids, and probably with age. Measures of enzyme activity can predict the response of bone formation markers to therapeutic glucocorticoids. This review summarises the data relating to 11beta-HSD expression and activity in human bone and describes how this has implications for age-related, inflammation-associated, and glucocorticoid-induced osteoporosis.