Pathogenesis of Age-Related Osteoporosis Impaired Mechano-Responsiveness of Bone Is Not the Culprit 英文参考文献.docVIP

PathogenesisofAge-RelatedOsteoporosis:Impaired Mechano-ResponsivenessofBoneIsNottheCulprit OlliV.Leppa¨nen1,2,HarriSieva¨nen3,JarkkoJokihaara1,2,4,IlariPajama¨ki1,2,PekkaKannus1,2,3 TeppoL.N.Ja¨rvinen1,2 , * 1MedicalSchoolandtheInstituteofMedicalTechnology,UniversityofTampere,Tampere,Finland,2DivisionofOrthopaedicsandTraumatology,DepartmentofTrauma, MusculoskeletalSurgeryandRehabilitation,TampereUniversityHospital,Tampere,Finland,3TheBoneResearchGroup,UKK-Institute,Tampere,Finland,4Departmentof Orthopaedics,UniversityofBritishColumbia,Vancouver,BritishColumbia,Canada Abstract Background:Accordingtoprevailingunderstanding,skeletalmechano-responsivenessdeclineswithageandthisapparent failure of the mechano-sensory feedback system has been attributed to the gradual bone loss with aging (age-related osteoporosis). The objective of this study was to evaluate whether the capacity of senescent skeleton to respond to increasedloadingisindeedreducedascomparedtoyoungmatureskeleton. MethodsandFindings:108maleand101femaleratswererandomlyassignedintoExerciseandControlgroups.Exercise groups were subjected to treadmill training either at peak bone mass between 47–61 weeks of age (Mature) or at senescencebetween75–102weeksofage(Senescent).Afterthetrainingintervention,femoralnecksanddiaphysiswere evaluated with peripheral quantitative computed tomography (pQCT) and mechanical testing; the proximal tibia was assessedwithmicrocomputedtomography(mCT).ThemCTanalysisrevealedthatthesenescentbonetissuewasstructurally deteriorated compared to the mature bone tissue, confirming the existence of age-related osteoporosis. As regards the mechano-responsiveness,theusedloadingresultedinonlymarginalincreasesinthebonesofthematureanimals,while significantexercise-inducedincreaseswereobservedvirtuallyinallbonetraitsamongthesenescentrats. Conclusion:Thebonesofsenescentratsdisplayedaclearabilitytorespondtoanexerciseregimenthatfailedtoinitiatean adaptiveresponseinmatureanimals.Thus,ourobservationssugge