Glucocorticoids in bone and joint disease: the good, the bad and the uncertain.
Therapeutic glucocorticoids are widely used to treat a variety of inflammatory conditions. However, the beneficial anti-inflammatory effects of glucocorticoids are limited by their detrimental effects on bone, including decreased bone density and increased fracture risk. Glucocorticoids adversely affect bone because they inhibit the amount of bone formed by osteoblasts. Surprisingly, through the expression of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme, osteoblasts can generate active glucocorticoids (cortisol and/or prednisolone) from their inactive counterparts (cortisone and/or prednisone). 11beta-HSD1 activity in an individual predicts the impact of glucocorticoids on bone. 11beta-HSD1 expression within bone also increases with age and inflammation. This implicates locally produced glucocorticoids in age-related and inflammation-associated osteoporosis. Glucocorticoids are also generated by synovial tissue through the expression of 11beta-HSD1. Activity increases with joint inflammation and could represent a local anti-inflammatory system. The recognition that peripheral tissues generate glucocorticoids suggests that, for conditions associated with ageing or inflammation, one should consider glucocorticoid activity beyond the circulation.
University of Birmingham, Queen Elizabeth Hospital. m.s.cooper@bham.ac.uk
Mark S
MS
Cooper
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D001847:Bone Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050723:Fractures, Bone / Q000209:etiology; D005938:Glucocorticoids / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007592:Joint Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism
D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1