In healthy individuals measures of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity predict the change in bone formation markers in response to therapeutic glucocorticoids. It is unclear whether these measures remain predictive in inflammatory disease. We therefore examined whether 11β-HSD1 activity predicts changes in bone markers and bone mineral density (BMD) in patients with inflammatory bowel disease (IBD) treated with therapeutic glucocorticoids. Prospective and cross-sectional studies were carried out in patients attending a gastroenterology clinic with active (n = 39) or clinically inactive (n = 34) IBD and healthy controls (n = 51). Urinary corticosteroid metabolite profiles were obtained on a spot urine sample and total corticosteroid metabolite excretion and 11β-HSD1 activity (measured as the ratio of tetrahydrocortisol to tetrahydrocortisone metabolites, [THF+alloTHF]/THE) determined. Patients with active disease were treated with an 8-week reducing course of oral prednisolone. The (THF+alloTHF)/THE ratio was significantly increased in patients with IBD, even those in clinical remission. The baseline (THF+alloTHF)/THE ratio failed to predict the decrease in bone formation markers or hip BMD. Measures of 11β-HSD activity do not predict bone loss during glucocorticoid treatment of active IBD, probably due to disease-related increases in 11β-HSD1 activity. Our observation of elevated 11β-HSD1 activity in clinically inactive IBD implicates gastrointestinal glucocorticoid activation in the maintenance of disease remission.
|Translated title of the contribution||Can 11β-hydroxysteroid dehydrogenase activity predict the sensitivity of bone to therapeutic glucocorticoids in inflammatory bowel disease?|
|Article number||Epub 2011 Jun 22|
|Number of pages||6|
|Journal||Calcified Tissue International|
|Publication status||Published - Sep 2011|
Bibliographical noteTitle of Publication Reviewed: Can 11β-hydroxysteroid dehydrogenase activity predict the sensitivity of bone to therapeutic glucocorticoids in inflammatory bowel disease?
Author of Publication Reviewed: Cooper MS, Kriel H, Sayers A, Fraser WD, Williams AM, Stewart PM, Probert CS, Tobias JH
Other: PMID: 21695543