Among the mechanisms contributing to obesity-associated osteoporosis, the following stand out: proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and adipokines (leptin and adiponectin); changes in gut microbiota and intestinal permeability; insulin resistance; oxidative stress; and free or EV-carried non-coding RNAs. Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.