The receptor activator of nuclear factor kappa (RANK)-RANK ligand-osteoprotegerin (OPG) system and pro-inflammatory cytokines, metabolite imbalance such as bilirubin, sclerostin, and insulin-like growth factor-1 accounted for osteoporosis, while insulin resistance and obesity in NAFLD and hyperammonemia, low branched-chain amino acids, and hypogonadism in liver cirrhosis resulted in sarcopenia in liver disease. The gene discussed is TNFRSF11A; the disease is obesity due to melanocortin 4 receptor deficiency.