Exp Clin Endocrinol Diabetes 2014; 122 - P040
DOI: 10.1055/s-0034-1372057

Higher 24-h urinary free cortisone, but not cortisol is associated with impaired cortical bone status at the proximal radius in healthy children

L Shi 1, A Sánchez-Guijo 2, MF Hartmann 2, E Schönau 3, SA Wudy 2, T Remer 1
  • 1IEL-Nutritional Epidemiology, University of Bonn, DONALD Study Center at the Research Institute of Child Nutrition Dortmund, Dortmund, Germany
  • 2Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus-Liebig-University, Gießen, Germany
  • 3Children's Hospital, University of Cologne, Cologne, Germany

Introduction: Impaired bone status is often observed in disease states with overproduction of glucocorticoids. However, whether already moderate variations in glucocorticoid levels may impact on bone is controversially discussed. Since protein intake affects both bone and glucocorticoid status, we herein examined in healthy children and adolescents the association between endogenous glucocorticoids and cortical bone after controlling for protein intake.

Methods: Proximal forearm bone parameters were measured by peripheral quantitative computed tomography. 175 subjects (87 males, aged 6 – 18 y) with two 24-h urine samples, collected 1 y before and at bone measurement, were included. Major glucocorticoid metabolites determined by GC-MS were summed (ΣC21) to assess daily overall cortisol secretion; urinary free cortisol (UFF) and cortisone (UFE) measured by HPLC-MS/MS were summed (UFF+UFE) as an indicator for potentially bioactive free glucocorticoids.

Results: Both ΣC21 and UFF+UFE were negatively (P < 0.05) associated with volumetric bone mineral density (vBMD), bone mineral content (BMC), and in trend with cortical area (CA) (p < 0.1). ΣC21 was additionally significant for polar bone strength strain index. UFE alone, but not UFF, was significant for vBMD, BMC, and CA. Children with higher ΣC21 or UFE (3rd-Tertile) showed 3.6 – 4.9 mg/mm lower BMC and 16 – 20 mg/cm3 lower vBMD than those in the 1st -Tertile. Glucocorticoid-bone associations reached significance mostly only after adjustment for the biomarker for protein intake, i.e., 24-h urinary nitrogen.

Conclusion: Higher glucocorticoid levels, even in the physiological range, apparently already have a negative impact on bone status during growth. The observed relationship particularly of urinary free cortisone with bone may reflect this metabolite's potential as a specific source of cortisol synthesis in bone cells, underlining the importance of 11β-HSD1 in peripheral tissues.

Supported by DFG, 1RE 753/7 – 2, 2WU 148/7 – 2