Ghrelin and Bone Metabolism in Adolescent Girls with Anorexia Nervosa and Healthy Adolescents

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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. 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. 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. 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.