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

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Abstract

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.

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Acknowledgement

We thank the patients and volunteers who participated in the study and Proctor and Gamble Pharmaceuticals for funding this work.

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Authors and Affiliations

  1. Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK

    Mark S. Cooper & Paul M. Stewart

  2. Clinical Science at South Bristol, University of Bristol, Bristol, UK

    Hashir Kriel, Amanda M. Williams & Chris S. Probert

  3. Academic Rheumatology, Clinical Science at North Bristol, University of Bristol, Bristol, UK

    Adrian Sayers & Jonathan H. Tobias

  4. Clinical Chemistry, University of Liverpool, Liverpool, UK

    William D. Fraser

Authors
  1. Mark S. Cooper
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  2. Hashir Kriel
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  3. Adrian Sayers
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  4. William D. Fraser
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  5. Amanda M. Williams
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  6. Paul M. Stewart
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  7. Chris S. Probert
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  8. Jonathan H. Tobias
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Corresponding author

Correspondence to Mark S. Cooper.

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The authors have stated that they have no conflict of interest.

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Cooper, M.S., Kriel, H., Sayers, A. et al. Can 11β-Hydroxysteroid Dehydrogenase Activity Predict the Sensitivity of Bone to Therapeutic Glucocorticoids in Inflammatory Bowel Disease?. Calcif Tissue Int 89, 246–251 (2011). https://doi.org/10.1007/s00223-011-9512-2

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  • DOI: https://doi.org/10.1007/s00223-011-9512-2

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