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

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 ...