Can 11β-Hydroxysteroid Dehydrogenase Activity Predict the Sensitivity of Bone to Therapeutic Glucocorticoids in Inflammatory Bowel Disease?

Mark S. Cooper, Hashir Kriel, Adrian Sayers, William D. Fraser, Amanda M. Williams, Paul M. Stewart, Chris S. Probert, Jonathan H. Tobias

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In healthy individuals measures of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-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 11ß-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 11ß-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 11ß-HSD activity do not predict bone loss during glucocorticoid treatment of active IBD, probably due to disease-related increases in 11ß-HSD1 activity. Our observation of elevated 11ß-HSD1 activity in clinically inactive IBD implicates gastrointestinal glucocorticoid activation in the maintenance of disease remission.
Original languageEnglish
Pages (from-to)246-251
Number of pages6
JournalCalcified Tissue International
Volume89
Issue number3
DOIs
Publication statusPublished - Jun 2011

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