Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass

Abstract

Obese children, particularly those who have fractured, have reduced body size-adjusted total body and regional bone mass. We performed an observational cross-sectional cohort study to determine the relationship between adipokines (leptin and adiponectin), bone-derived cytokines and bone turnover in children which may explain this observation. Participants aged 5–16 years were recruited into obese (BMI SDS 3.3 ± 0.6) and lean (BMI SDS 0.2 ± 1.0) groups and further subdivided into groups by fracture history. Free leptin (leptin/leptin soluble receptor) and adiponectin; RANK-ligand (RANKL), osteoprotegerin (OPG); Dickkopf-1 (DKK1); and the bone turnover markers procollagen type I amino propeptide (P1NP) and carboxy-terminal telopeptide of type I collagen (CTx). Total body and truncal fat mass were measured by DXA. Results: Free leptin (p > 0.0001) and adiponectin (p = 0.0002) were higher and lower in obese children respectively. OPG was lower in obese children (p = 0.01), being inversely related to free leptin (p = 0.009), total body and truncal fat mass (both p = 0.01). RANKL was inversely related to free leptin in children with prior fracture (p = 0.03). CTx was higher in obese children (p = 0.003). Free leptin was positively associated with both CTx (p = 0.03) and P1NP (p = 0.02). DKK1 was inversely related to adiponectin (p = 0.02). Conclusion: Bone formation relative to resorption was reduced in obese children; this difference was accentuated in those with prior fracture. Adipokines may regulate these changes. Osteoprotegerin may play a fundamental role in the failure of obese children to accrue bone mass appropriately.