Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta

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dc.contributor.authorBerman, Alycia G.
dc.contributor.authorWallace, Joseph M.
dc.contributor.authorBart, Zachary R.
dc.contributor.authorAllen, Matthew R.
dc.contributor.departmentAnatomy and Cell Biology, School of Medicineen_US
dc.date.accessioned2019-04-29T18:20:59Z
dc.date.available2019-04-29T18:20:59Z
dc.date.issued2016
dc.description.abstractOsteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests. RAL soaking resulted in significantly higher post-yield displacement (+75% in WT, +472% in oim; p<0.004), with no effect on ultimate load or stiffness, in both WT and oim animals. In experiment 2, eight-week old WT and oim male mice were treated for eight weeks with saline vehicle (VEH) or RAL. Endpoint measures included assessment of in vivo skeletal fractures, bone density/geometry and mechanical properties. In vivo skeletal fractures of the femora, assessed by micro CT imaging, were significantly lower in oim-RAL (20%) compared to oim-VEH (48%, p=0.047). RAL led to significantly higher DXA-based BMD (p<0.01) and CT-based trabecular BV/TV in both WT and oim animals compared to those treated with VEH. Fracture toughness of the femora was lower in oim mice compared to WT and improved with RAL in both genotypes. These results suggest that raloxifene reduces the incidence of fracture in this mouse model of oim. Furthermore, they suggest that raloxifene's effects may be the result of both cellular (increased bone mass) and non-cellular (presumably changes in hydration) mechanisms, raising the possibility of using raloxifene, or related compounds, as a new approach for treating bone fragility associated with OI.en_US
dc.description.sponsorshipS10 RR023710/RR/NCRR NIH HHS/United Statesen_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationBerman AG, Wallace JM, Bart ZR, Allen MR. Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta. Matrix Biol. 2016 May-Jul;52-54:19-28. doi: 10.1016/j.matbio.2015.12.008. Epub 2015 Dec 18. PubMed PMID: 26707242.en_US
dc.identifier.urihttps://hdl.handle.net/1805/18990
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.matbio.2015.12.008en_US
dc.relation.journalInternational Society for Matrix Biologyen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectBone Density Conservation Agentsen_US
dc.subjectFemoral Fracturesen_US
dc.subjectOsteogenesis Imperfectaen_US
dc.subjectRaloxifene Hydrochlorideen_US
dc.titleRaloxifene reduces skeletal fractures in an animal model of osteogenesis imperfectaen_US
dc.typeArticleen_US
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