Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor

Objective To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR). Design and patients The Longitudinal Ageing Study Amsterdam (LASA), a population-based cohort study in older men and women. Measurements Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self-report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BdI) were genotyped by Taqman (n = 858). Results Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = -0 center dot 135, P = 0 center dot 04). No significant associations in men were found. Female 9beta G-allele carriers had 50 center dot 2 nmol/l lower cortisol and 1 center dot 2 lower free cortisol levels than AA homozygotes [P = 0 center dot 01 for (free) cortisol]. Furthermore, female BdI GG homozygotes had 54 center dot 8 nmol/l higher cortisol levels than C-carriers (P = 0 center dot 03). In the total population, BdI GG homozygotes had 0 center dot 05 g/cm(2) lower trochanteric region BMD (P = 0 center dot 03). For the other GR gene polymorphisms, no significant associations were found. Conclusions Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BdI GG homozygotes had higher serum cortisol levels, and BdI GG homozygotes had lower trochanteric region BMD in the total population.