Sclerostin Antibody as a Treatment for Osteogenesis Imperfecta.
dc.contributor.author | Sinder, Benjamin P. | en_US |
dc.date.accessioned | 2015-01-30T20:11:12Z | |
dc.date.available | NO_RESTRICTION | en_US |
dc.date.available | 2015-01-30T20:11:12Z | |
dc.date.issued | 2014 | en_US |
dc.date.submitted | 2014 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/110366 | |
dc.description.abstract | Osteogenesis Imperfecta (OI) is a genetic collagen disorder characterized by increased fracture risk, and typically presents the strongest in children. Current efforts to reduce fracture rate in OI include treatment with anti-resorptive bisphosphonates. While bisphosphonate therapy has shown efficacy at increasing bone mass in the axial skeleton, there have not been consistent reductions in long bone fracture risk. New treatments which increase bone mass throughout the OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for OI and functions by stimulating osteoblastic bone formation via the canonical wnt signaling pathway. We have characterized the use of Scl-Ab in a Brtl/+ mouse model of moderately severe Type IV OI. Treatment of rapidly growing, and adult, Brtl/+ mice demonstrate Scl-Ab stimulated bone formation, increased cortical and trabecular bone mass, and improved long bone strength. Using fluorescent guided analysis to control for tissue age, material composition (raman spectroscopy) and material property (nanoindentation) were also assessed. Scl-Ab did not effect the elastic modulus, did influence material composition, and differing patterns across tissue age were observed in rapidly growing vs adult animals. Collectively, these animal studies suggest that Scl-Ab may represent a new potential therapy for the treatment of OI. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | bone | en_US |
dc.title | Sclerostin Antibody as a Treatment for Osteogenesis Imperfecta. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Biomedical Engineering | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.contributor.committeemember | Kozloff, Kenneth Michael | en_US |
dc.contributor.committeemember | McCauley, Laurie Kay | en_US |
dc.contributor.committeemember | Caird, Michelle Sugiyama | en_US |
dc.contributor.committeemember | Kohn, David H. | en_US |
dc.subject.hlbsecondlevel | Biomedical Engineering | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/110366/1/bpsinder_1.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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