Date of Award

6-2012

Degree Name

MS in Biomedical Engineering

Department

Biomedical and General Engineering

Advisor

Scott Hazelwood

Abstract

The purpose of this study is to characterize the compact bone remodeling of the ovariectomized ewe and its effectiveness as an animal model for studies of postmenopausal osteoporosis. The use of animal models is a beneficial way to evaluate the effectiveness of medical devices and therapeutic agents for treating diseases. The ovine model is an attractive option because of its large size and similar bone remodeling to humans. However, this species, like most animals, does not undergo a natural menopause, making an ovariectomy necessary for studies of estrogen depletion. The OVX (ovariectomized) sheep has been widely accepted as a model for loss of BMD. However, even with its advantages seasonality has been shown to have an effect on the bone remodeling in the ovine model. Thus, this study focused on characterizing the seasonal and anatomical variation in the compact bone remodeling in the ovine model. In doing so, 28 skeletally mature Columbia-Rambouillet cross ewes underwent an ovariectomy. The animals were divided into groups of 7 based on each season: autumn, winter, spring, and summer. During its specified season each group of 7 underwent ovariectomy and then was sacrificed 12 months post-surgery. The radii and ulnae were harvested and then divided into 6 anatomical locations: craniolateral, cranial, craniomedial, craniolateral, caudal, and caudomedial. This allowed for analysis through the fabrication of microradiographs. Histomorphometric analysis involved measurements to quantify the bone volume to tissue volume ratio, the percent of tissue and material remodeling, the mean secondary osteonal radius, and number of tissue and material cement line interfaces. Densitometry analysis was then performed to determine the density of each sector relative to an aluminum step wedge, serving as the key. Using a 2-way repeated measures ANOVA statistical analysis was performed to evaluate for seasonal and anatomical differences as well as a possible interaction between season and anatomical region. The OVX data showed significant seasonal and anatomical differences as well as seasonality within anatomical section in the remodeling parameters. When this data was combined with earlier data from a control, sham-cohort from the same experiment a 3-way ANOVA was also performed to evaluate the effects of season, anatomical sector, and treatment on the remodeling parameters. Again, there was significant seasonal, anatomical, and treatment differences, as well as interactions of all three. The results of this study showed that varying levels of remodeling occurs in the adult OVX ovine model and differences between the control and OVX model can be attributed to seasonal and anatomical variations. Thus, it will be an important consideration when developing new test protocols for research incorporating the sheep model for studying osteoporosis.

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