Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents

Context: Anorexia nervosa ( AN) in adolescents is associated with low bone mineral density (BMD) and increases in ghrelin secretion, an orexigenic GH secretagogue that stimulates osteoblast proliferation in vitro. Objective: We hypothesized that ghrelin may have independent effects on bone in AN adolescents. Study Design, Subjects, and Outcome Measures: Frequent sampling was performed overnight every 30 min for 12 h in 23 adolescent AN girls aged 12 - 18 yr and 21 controls of comparable maturity. Ghrelin, leptin, cortisol, and GH secretion were examined using Cluster and deconvolution. We measured BMD and body composition (dual-energy x-ray absorptiometry) and carboxy-terminal peptide of type I procollagen and N-telopeptide levels. Results: In healthy adolescents, ghrelin secretion strongly predicted BMD; secretory burst mass being the strongest predictor of lumbar spine (LS) bone mineral apparent density (BMAD) (r = 0.66, P = 0.003), LS BMAD z-scores (BMAD- z) (r = 0.59, P = 0.01), hip BMD (r = 0.55, P = 0.02), and hip BMD-z (r = 0.52, P = 0.03). When body composition measures ( body mass index, lean and fat mass), and hormonal predictors (GH, IGF-I, cortisol, leptin, and estradiol) were entered into a regression model with ghrelin secretion to determine independent BMD predictors, ghrelin was the strongest predictor of LS BMAD, BMAD- z, hip BMD, and hip BMD-z, contributing to 43, 30, 26, and 19% of the variability, respectively, independent of GH or cortisol effects. Conversely, in AN, ghrelin secretion did not predict LS BMAD or hip-z and weakly predicted LS BMAD-z and hip BMD. Ghrelin did not predict carboxy-terminal peptide of type I procollagen or N-telopeptide/creatinine, which were predicted by GH and cortisol. Conclusion: Ghrelin secretion predicts bone density independent of body composition, the GH-IGF-I axis, cortisol, or estradiol in healthy girls but not in those with AN.