Relationships of acylated and des-acyl ghrelin levels to bone mineralization in obese children and adolescents.

AIMS: Bodyweight is a significant predictor of bone mass. Hormonal factors are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. Very recently, the orexigenic hormone ghrelin has also been implicated in bone metabolism. In this study we examined the associations of circulating acylated and des-acyl ghrelin concentrations with measures of bone in a group of obese children and adolescents as well as in a group of healthy control children. We also determined whether the associations were independent of body composition, chronological age, gender, Tanner stage, and leptin, glucose, insulin and insulin-like growth factor (IGF)-1 levels.

METHODS: We performed a prospective cross-sectional study of 100 obese children [age, 8.9 (8.3 to 9.4); BMI-Standard Deviation Score (SDS), 2.2 (2.0 to 2.3)], and 100 age-matched lean healthy subjects. Fasting insulin, leptin, IGF-1, acylated and total ghrelin were measured by radioimmunoassay. Des-acyl ghrelin values were calculated as total ghrelin minus acylated ghrelin. Whole body (WB) and lumbar spine (LS) BMD, and BMC as well as body composition were assessed by DXA (Hologic QDR-4500W). LS volumetric BMD (BMAD) was estimated using the formula of Katzman (BMC/area(1.5)), while WB BMC data were expressed as BMC/height.

RESULTS: Backward linear regression analysis was performed for individual groups, with age, gender, Tanner stage, weight, height, body composition (lean and fat mass), acylated ghrelin, des-acyl ghrelin, leptin, glucose, insulin, and IGF-1, entered into the model. In healthy children, acylated ghrelin was a significant and independent negative predictor of WB BMD, and WB BMC/height, while lean mass was positively associated significantly with these bone measures. In contrast, in obese children, a positive significant association was observed between des-acyl ghrelin and WB BMD as well as WB BMC/height, along with lean mass, and to a lesser degree, with fat mass. Acylated as well as des-acyl ghrelin were not significant predictors of LS BMD and LS BMAD in obese as well as control children.

CONCLUSIONS: The results of this investigation indicate that the influence of the two distinct isoforms of ghrelin on BMD is mediated by specific body composition parameters in obese and control healthy children.