Background　and　Objective:　Screw　loosening　remains　a　prominent　problem　for　osteoporotic　patients　undergoing　pedicle　screw　fixation　surgeries　but　its　underlying　mechanisms　are　not　fully　understood.　This　study　sought　to　examine　the　interactive　effect　of　craniocaudal　or　axial　cyclic　loading　(toggling)　and　osteoporosis　on　screw　fixation.　Methods:　QCT-based　finite　element　models　of　normal　(n　=　7;　vBMD　=　156　±　13　mg/cm3)　and　osteoporotic　vertebrae　(n　=　7;　vBMD　=　72　±　6　mg/cm3)　were　inserted　with　pedicle　screws　and　loaded　with　or　without　craniocaudal　toggling.　Among　them,　a　representative　normal　vertebra　(age:　55;　BMD:　140　mg/cm3)　and　an　osteoporotic　vertebra　(age:　64;　BMD:　79　mg/cm3)　were　also　loaded　with　or　without　axial　toggling.　The　individual　and　interactive　effects　of　craniocaudal　toggling　and　osteoporosis　on　screw　fixation　strength　(the　force　when　the　pull-up　displacement　of　the　screw　head　reached　1　mm)　and　bone　tissue　failure　(characterized　by　equivalent　plastic　strain)　were　examined　by　repeated　measure　ANOVA.　Results:　A　significant　interactive　effect　between　craniocaudal　toggling　and　osteoporosis　on　screw　fixation　strength　was　detected　(p　=　0.008).　Specifically,　craniocaudal　toggling　led　to　a　marked　decrease　in　the　fixation　strength　(68%,　p　＜　0.05)　and　stiffness　(83%,　p　＜　0.05)　only　in　the　osteoporotic　vertebrae　but　had　no　effect　on　screw　fixation　strength　and　stiffness　of　the　normal　vertebrae　(p　＞　0.05).　Likewise,　most　of　the　bone　tissues　around　the　screw　in　the　osteoporotic　vertebrae　yielded　following　craniocaudal　toggling　whereas　this　result　was　not　seen　in　the　normal　vertebrae.　The　axial　toggling　had　no　significant　effect　on　bone　tissue　failure　as　well　as　pedicle　screw　fixation　in　normal　or　osteoporotic　vertebrae.　Conclusions:　Craniocaudal　toggling　substantially　reduces　the　screw　fixation　strength　of　the　osteoporotic　vertebrae　by　progressively　increasing　tissue　failure　around　the　screw,　and　therefore　may　contribute　to　the　higher　rates　of　screw　loosening　in　osteoporotic　compared　to　normal　patients,　whereas　axial　toggling　is　not　a　risk　factor　for　pedicle　screw　loosening　in　normal　or　osteoporotic　patients.　©　2023　Elsevier　B.V.