The interplay between chronic inflammation (increased IL-6 and TNF-α leading to osteoclast activation and muscle protein breakdown, increased NF-κB and RANKL expression), muscle-bone crosstalk dysregulation (myostatin overexpression, irisin and osteocyte dysfunction), metabolic dysfunction, and tumor microenvironment alterations (IGF-1 suppression and adipokines and endocrine dysfunction) underlies the association between osteopenia/osteosarcopenia and poor survival in GI cancers (44, 45). The gene discussed is FNDC5; the disease is Osteopenia.