As　a　systemic　disease,　osteoporosis　(OP)　results　in　bone　density　loss　and　fracture　risk,　particularly　in　the　hip　and　vertebrae.　However,　the　underlying　molecular　mechanisms　of　OP　development　have　not　been　fully　illustrated.　N6-Methyladenosine　(m6A)　is　the　most　abundant　modification　of　mRNAs,　which　is　involved　in　many　of　pathological　processes　in　aging　disease.　However,　its　role　and　regulatory　mechanism　in　OP　remains　unknown.　Here,　we　aimed　to　investigate　the　roles　of　m6A　and　its　demethylase　FTO　in　OP　development.　The　results　showed　that　m6A　methylated　RNA　level　was　up-regulated　in　the　bone　marrow　mesenchymal　stem　cells　(BMSCs)　from　patients　with　OP.　The　level　of　N6-methyladenosine　demethylase　FTO　was　consistently　decreased　in　the　BMSCs　from　patients　with　OP.　Functionally,　lentivirus-mediated　FTO　overexpression　in　normal　BMSCs　to　compromised　osteogenic　potential.　Mechanism　analysis　further　suggested　that　FTO　overexpression　decreased　the　m6A　methylated　and　total　level　of　runt　related　transcription　factor　2　(Runx2)　mRNA,　subsequently　inhibited　osteogenic　differentiation.　We　found　that　FTO　inhibition　could　effectively　improve　the　bone　formation　in　ovariectomized　osteoporotic　mice　in　vivo.　Together,　these　results　reveal　that　RNA　N6-methyladenosine　demethylase　FTO　promotes　osteoporosis　through　demethylating　runx2　mRNA　and　inhibiting　osteogenic　differentiation.