11β-Hydroxysteroid Dehydrogenase Type 1 Activity Predicts the Effects of Glucocorticoids on Bone

• Published in: The journal of clinical endocrinology and metabolism Vol. 88; no. 8; pp. 3874 - 3877
• Main Authors: Cooper, Mark S., Blumsohn, Aubrey, Goddard, Philippa E., Bartlett, William A., Shackleton, Cedric H., Eastell, Richard, Hewison, Martin, Stewart, Paul M.
• Format: Journal Article
• Language: English
• Published: Washington Oxford University Press 01.08.2003; Copyright by The Endocrine Society
• Subjects: 11β-Hydroxysteroid dehydrogenase; Bone growth; Bone resorption; Bone turnover; Collagen (type I); Dehydrogenases; Glucocorticoids; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Prednisolone; Prednisone; Steroids
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-022025

Individual susceptibility to glucocorticoid-induced osteoporosis is difficult to predict clinically. We recently characterized expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-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 11β-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 11β-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 11β-HSD1 activity may predict individual susceptibility to glucocorticoid-induced osteoporosis, and these data should facilitate the development of bone-sparing glucocorticoids.