In the light of these evidences and of the increasing interest on the polyphenol effects on childhood obesity, the aim of this paper were: (a) to deepen the mechanisms of bone impairment in obese children and adolescents, through the evaluation of the serum levels of RANKL and OPG together with the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs), and (b) to evaluate in vitro, the effects of polyphenols from sweet cherry extracts on osteoclastogenesis, as possible dietary treatment to improve bone health in obesity. Here, TNFRSF11B is linked to obesity due to melanocortin 4 receptor deficiency.