Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

dc.contributor.authorNewman, Christopher L.
dc.contributor.authorCreecy, Amy
dc.contributor.authorGranke, Mathilde
dc.contributor.authorNyman, Jeffry S.
dc.contributor.authorTian, Nannan
dc.contributor.authorHammond, Max A.
dc.contributor.authorWallace, Joseph M.
dc.contributor.authorBrown, Drew M.
dc.contributor.authorChen, Neal
dc.contributor.authorMoe, Sharon M.
dc.contributor.authorAllen, Matthew R.
dc.contributor.departmentDepartment of Anatomy & Cell Biology, IU School of Medicineen_US
dc.date.accessioned2017-06-19T17:38:34Z
dc.date.available2017-06-19T17:38:34Z
dc.date.issued2016-01
dc.description.abstractPatients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationNewman, C. L., Creecy, A., Granke, M., Nyman, J. S., Tian, N., Hammond, M. A., … Allen, M. R. (2016). Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease. Kidney International, 89(1), 95–104. http://doi.org/10.1038/ki.2015.315en_US
dc.identifier.issn1523-1755en_US
dc.identifier.urihttps://hdl.handle.net/1805/13080
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/ki.2015.315en_US
dc.relation.journalKidney Internationalen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectBone Density Conservation Agentsen_US
dc.subjectpharmacologyen_US
dc.subjectFemuren_US
dc.subjectdrug effectsen_US
dc.subjectPolycystic Kidney, Autosomal Dominanten_US
dc.subjectdrug therapyen_US
dc.subjectRaloxifene Hydrochlorideen_US
dc.subjectRenal Insufficiency, Chronicen_US
dc.subjectSpineen_US
dc.titleRaloxifene improves skeletal properties in an animal model of cystic chronic kidney diseaseen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nihms722820.pdf
Size:
496.34 KB
Format:
Adobe Portable Document Format