Osteocytes,　situated　within　the　lacunocanalicular　network　(LCN)　of　the　bone　matrix,　play　crucial　roles　in　sensing　mechanical　signals　and　orchestrating　bone　adaptive　responses.　Alterations　in　LCN　structure　could　significantly　modify　the　fluid　dynamic　microenvironment　of　osteocytes,　thereby　influencing　bone　mechanoresponses　(BMRs).　However,　a　comprehensive　understanding　of　this　tissue　remains　elusive.　In　this　study,　a　multi-scale　model　of　whole　bone-LCN　was　developed　to　systematically　investigate　the　effects　of　lacunocanalicular　morphology　(lacunar　volume　[Lc.V]　and　canalicular　area　[Ca.S])　and　network　architecture　(lacunar　density　[Lc.rho]　and　canalicular　density　[Ca.rho])　on　fluid　shear　stress　(FSS)　within　the　LCN　and　BMR　predicted　by　fluid　flow.　Furthermore,　the　relationships　between　fluid　flow　within　the　LCN　and　BMRs　were　examined　in　two　specific　scenarios:　aging　and　lactation.　Results　demonstrated　that　changes　in　lacunocanalicular　morphology　(Lc.V　and　Ca.S)　primarily　influenced　the　intensity　of　fluid　flow,　while　alterations　in　the　LCN　(Lc.rho　and　Ca.rho)　largely　affected　the　distribution　of　fluid　flow.　Increases　in　Lc.V　or　decreases　in　Ca.S　increased　FSS,　whereas　decreases　in　Lc.rho　or　increases　in　Ca.rho　reduced　FSS.　Compared　with　other　structural　parameters,　alterations　in　Ca.rho　had　the　greatest　effect　on　FSS,　while　BMR　primarily　depended　on　changes　in　Lc.V　and　Ca.S.　In　agreement　with　experimental　observations,　aging-　or　lactation-induced　changes　in　LCN　structure　(and　fluid　dynamics)　were　associated　with　reduced　(-50%)　or　increased　(+20%)　bone　responses　to　mechanical　loading,　respectively.　These　findings　suggest　that　modifications　in　lacunocanalicular　morphology　and　network　architecture　can　substantially　impact　the　fluid　dynamic　microenvironment　for　mechanosensing　osteocytes　and,　consequently,　BMRs.