Obesity is a state of low-grade systematic inflammation, in which pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-17 [14], and adipokines, such as leptin [15], released from the dysfunctional adipose tissue into the circulation, may regulate the OPG-RANKL-RANK axis in bones, with main final effect, the inhibition of bone formation and the acceleration of bone resorption. This evidence concerns the gene TNFSF11 and obesity due to melanocortin 4 receptor deficiency.