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

J Clin Endocrinol Metab. 2003 Aug;88(8):3874-7. doi: 10.1210/jc.2003-022025.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Adult
  • Biomarkers
  • Bone Density
  • Bone Resorption / metabolism
  • Bone and Bones / drug effects*
  • Glucocorticoids / pharmacology*
  • Humans
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Male
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects
  • Prednisolone / blood
  • Steroids / blood
  • Steroids / urine


  • Biomarkers
  • Glucocorticoids
  • Steroids
  • Prednisolone
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • HSD11B2 protein, human