The　skeleton　accommodates　changes　in　mechanical　environments　by　increasing　bone　mass　under　increased　loads　and　decreasing　bone　mass　under　disuse.　However,　little　is　known　about　the　adaptive　changes　in　micromechanical　behavior　of　cancellous　and　cortical　tissues　resulting　from　loading　or　disuse.　To　address　this　issue,　in　vivo　tibial　loading　and　hindlimb　unloading　experiments　were　conducted　on　16　week-old　female　C57BL/6J　mice.　Changes　in　bone　mass　and　tissue-level　strains　in　the　metaphyseal　cancellous　and　midshaft　cortical　bone　of　the　tibiae,　resulting　from　loading　or　unloading,　were　determined　using　microCT　and　finite　element　(FE)　analysis,　respectively.　We　found　that　loading-　and　unloading　induced　changes　in　bone　mass　were　more　pronounced　in　the　cancellous　than　cortical　bone.　Simulated　FE-loading　showed　that　a　greater　proportion　of　elements　experienced　relatively　lower　longitudinal　strains　following　load-induced　bone　adaptation,　while　the　opposite　was　true　in　the　disuse　model.　While　the　magnitudes　of　maximum　or　minimum　principal　strains　in　the　metaphyseal　cancellous　and　midshaft　cortical　bone　were　not　affected　by　loading,　strains　oriented　with　the　long　axis　were　reduced　in　the　load-adapted　tibia　suggesting　that　loading　-induced　micromechanical　benefits　were　aligned　primarily　in　the　loading　direction.　Regression　analyses　demonstrated　that　bone　mass　was　a　good　predictor　of　bone　tissue　strains　for　the　cortical　bone　but　not　for　the　cancellous　bone,　which　has　complex-microarchitecture　and　spatially-variant　strain　environments.　In　summary,　loading-induced　micromechanical　benefits　for　cancellous　and　cortical　tissues　are　received　primarily　in　the　direction　of　force　application　and　cancellous　bone　mass　may　not　be　related　to　the　micromechanics　of　cancellous　bone.　(C)　2019　Elsevier　Ltd.　All　rights　reserved.