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Submitted on March 8, 2005
Accepted on June 28, 2005
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, MA, and Eating Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
* To whom correspondence should be addressed. E-mail: aklibanski{at}partners.org.
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 q30' for 12 h in 23 AN girls 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 (DXA), and PICP and N-telopetide (NTX) 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 (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 (BMI, 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 PICP or NTX/cr, 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.
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