A role for local corticosteroid metabolism by 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has been proposed in bone and adipose tissue physiology. In vivo, 11b-HSD1 predominantly converts inactive cortisone to active cortisol and enzyme activity is critically dependent on substrate concentration. To examine 11b-HSD1 activity in vivo we have analysed the relationship between serum cortisone and markers of bone turnover, BMD and adipose tissue mass in a cohort of women (n=135) and men (n=170) aged 60-75 years at baseline and followed up 4 years later.
0900 serum cortisone levels were negatively correlated with serum osteocalcin (r=-0.16, p=0.06 for women; r=-0.20, p=0.01 for men) but not urinary N-telopeptide of type I collagen (NTx)(r=-0.03 women; r=0.03 men, both NS). Negative correlations between serum cortisone and spine BMD were apparent (r=-0.18, p=0.04 for women; r=-0.14, p=0.07 for men) but cortisone did not predict femoral neck or total hip BMD or changes at any site over 4 years. In analyses adjusted for adiposity, osteoarthritis grade and life style variables the significance level did not change substantially (p=0.08 for both men and women). All these relationships were independent of cortisol concentrations.
In women, but not men, significant negative correlations were observed between serum cortisone and waist circumference (r=-0.19, p=0.03) and waist/hip ratio (r=-0.18, p=0.04) but not weight (r=-0.13, p=0.12). The relationship with BMI was of borderline significance (r=-0.16, p=0.07). Serum cortisone was not predicted by urinary measures of 11b-HSD1 or 11b-HSD2 activity.
In normal subjects 11b-HSD1 activity occurs within osteoblasts and adipose tissue in vivo. In bone, cortisone is converted to cortisol and in older subjects this activity negatively impacts on spinal BMD. The negative correlation of cortisone levels with waist circumference in women suggests a regional impact of 11b-HSD1 expression on adipose tissue with higher 11b-HSD1 activity apparently reducing central adiposity.