Hormones　such　as　fibroblast　growth　factor　21　(FGF21)　and　glucocorticoids　(GCs)　play　crucial　roles　in　bone　metabolism.　Long-term　treatment　with　corticosteroid　drugs　may　lead　to　glucocorticoid-related　osteoporosis,　and　previous　studies　have　defined　FGF21　as　a　factor　may　participate　in　bone　metabolism　and　most　studies　showed　that　it　negatively　regulates　bone　metabolism.　Herein　we　examine　the　interplay　between　these　factors　in　bone　metabolism.　In　our　study,　expressions　of　PPAR,　ALP,　and　TRAP-5b　were　compared　between　WT　mice　and　FGF21　inhibited　mice　(FGFi　mice)　and　WT　and　FGFi　mice　treated　with　adrenocorticotropic　hormone　(ACTH).　We　found　ACTH　treatment　significantly　blocked　ALP　decreases　in　FGFi　mice　as　compared　to　WT　whereas　TRAP-5b　expression　was　significantly　increased　(p＜0.01).　Collectively,　our　findings　suggest　the　following:　FGF21　may　serve　as　a　negative　regulator　of　bone　metabolism,　the　negative　regulation　of　bone　metabolism　via　FGF21　may　require　the　PPAR　gamma　pathway,　and　FGF21　may　be　involved　in　the　ACTH-Cortisol　axis-related　bone　mass　loss.