Circulating cortisone levels are associated with biochemical markers of bone formation and lumbar spine BMD: the Hertfordshire cohort study

Objective: Cortisone is an endogenous corticosteroid that has negligible intrinsic glucocorticoid activity but can be converted to the active corticosteroid cortisol by the enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1). 11?-HSD1 is expressed in osteoblasts and may play a role in determining susceptibility to glucocorticoid-induced osteoporosis. In intact osteoblasts enzyme activity, and thus cortisol generation, is dependent on substrate concentration with an almost linear increase in activity across the physiological range. We have therefore attempted to measure the impact of 11?-HSD1 activity on bone in vivo by examining the association of circulating cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort of women and men.Design and subjects: Baseline cross-sectional association study involving 135 women and 171 men aged 61–73 years from the Hertfordshire Cohort Study and a 4 year follow-up study examining changes in BMD.Measurements: Serum cortisone, cortisol and osteocalcin, and urinary type I collagen cross-linked N-telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at baseline and 4 years later.Results: In men serum cortisone levels were negatively correlated with serum osteocalcin (r = ?0·20, P = 0·01); a similar relationship was seen in women (r = ?0·16, P = 0·06). No correlation was seen between serum cortisone and urinary NTX (r = 0·03, P = 0·74 for women; r = ?0·03, P = 0·72 for men). A negative correlation was observed between serum cortisone and spine BMD in women (r = ?0·18, P = 0·04); a similar relationship was also seen in men (r =?0·14, P = 0·07). However, cortisone did not correlate with BMD at the femoral neck or total hip or changes in BMD at any site over time. In analyses adjusted for adiposity, osteoarthritis grade and a range of life-style variables, these relationships did not change substantially. All these relationships were independent of cortisol concentrations.Conclusions: The most plausible explanation for the association of circulating cortisone levels with osteocalcin is the presence of 11?-HSD1 activity within osteoblasts. The measurement of serum cortisone may independently give insights into the action of glucocorticoids on bone