11beta-hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone

Mark Cooper, A Blumsohn, PE Goddard, William Bartlett, Cedric Shackleton, R Eastell, Martin Hewison, Paul Stewart

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Individual susceptibility to glucocorticoid-induced osteoporosis is difficult to predict clinically. We recently characterized expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in human osteoblasts. This enzyme generates active cortisol (or prednisolone) from inactive cortisone (or prednisone) and regulates glucocorticoid action in vitro. We, thus, hypothesized that osteoblastic 11beta-HSD1 mediates susceptibility to glucocorticoid-induced osteoporosis. Twenty healthy males ingested 5 mg prednisolone twice daily for 7 d, and relationships between changes in bone turnover markers and urinary measures of corticosteroid metabolism were examined. The bone formation markers osteocalcin and N-terminal propeptide of type I collagen decreased in all subjects (P <0.001), but resorption markers were unchanged. The extent of fall in formation markers correlated with baseline 11beta-HSD1 activity with high activity predicting the greatest fall [for osteocalcin d 4 and 7, r = -0.58 and -0.56 (P <0.01); for N-terminal propeptide of type I collagen d 4, r = -0.51 (P <0.05)]. There was no correlation with measures of glucocorticoid inactivation or total corticosteroid metabolite production. Urinary measures of 11beta-HSD1 activity predict the response of bone formation markers to glucocorticoids, and this appears to reflect increased generation of active glucocorticoids within osteoblasts. Measures of 11beta-HSD1 activity may predict individual susceptibility to glucocorticoid-induced osteoporosis, and these data should facilitate the development of bone-sparing glucocorticoids.
Original languageEnglish
Pages (from-to)3874-3877
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Issue number8
Publication statusPublished - 1 Aug 2003


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