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Compositional and Material Properties of Rat Bone after Drug Treatment Open Access


Other title
dual energy X-ray absortiometry
electron probe micro analysis
finite element analysis
strontium ranelate
Type of item
Degree grantor
University of Alberta
Author or creator
Supervisor and department
Doschak, Michael (Pharmacy & Pharmaceutical Sciences)
Examining committee member and department
Adeeb,Samer (Civil & Environmental Engineering)
Duke, John ( SLOWPOKE Reactor Facility)
Elias, Anastasia (Chemical & Materials Engineering)
Unsworth, Larry (Chemical & Materials Engineering)
Wohl, Gregory (Mechanical Engineering, McMaster University)
Department of Biomedical Engineering

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Various X-ray imaging modalities, such as planar X-ray films, dual energy X-ray absorptiometry and computed tomography have been utilized to estimate bone strength for osteoporotic subjects. However, emerging cases of spontaneous femoral shaft fracture in osteoporotic patients after years of bisphosphonate (BP) medication and controversial gains in bone mineral density (BMD) after medication with strontium ranelate (SrR) have questioned the reliance of X-ray based imaging for accurately assessing fracture risk. Therefore, assessments of bone strength must further account for the influence of bone microarchitecture, changes in elemental composition and material properties of bone following potent drug interventions. Accordingly, in this thesis, the hypothesis was that osteoporotic bone would be influenced by alterations in bone microarchitecture, elemental composition and corresponding material properties following drug treatment, which in the aggregate, affect bone strength. In order to investigate the elemental composition and material properties, electron probe micro analysis and nanoindentation tests were applied to bone samples following SrR and/or BP treatment. The results confirmed that elemental strontium (Sr) was incorporated into bone predominantly in regions of new bone formation, through either the bone remodelling process or by incorporation during appositional and elongating bone growth. The material properties of bone were maintained following high dose strontium treatment, however, bone hardness was degraded following BP treatment. To measure bone strength, a simplified finite element analysis was established to calculate bone strength. Those analyses indicated that the strength of bone was positively related to the structural parameters of bone volume/tissue volume, BMD and fractal dimension. To further explore the controversial increase in BMD following Sr drug therapy, a series of known solution standards for Sr and calcium (Ca) were evaluated using micro-computed tomography (Micro-CT). Our results proved that for every 1 mole% increase in Sr/(Sr+Ca), there was a corresponding 6.4% increase in BMD using X-ray based Micro-CT. In summary, both elemental composition and material properties of rat bone were substantially altered following three months treatment with BP and/or SrR. Those alterations affected bone strength and microarchitecture, and the incorporation of Sr resulted in the bias of elevated BMD using X-ray based imaging modalities.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
The contents of this chapter have been previously published: Yuchin Wu, Samer M. Adeeb, M. John Duke, David Munoz-Paniagua, Michael R. Doschak. 2013. J Pharm Pharmaceuti Sci, 16(1):52-64

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