Date of Award

7-2008

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Advisor

Bateman, Ted A

Committee Member

Dean , Delphine

Committee Member

Graham , Robin M

Abstract

Osteoporosis is a condition characterized by a reduction in bone strength resulting in an overall increase in the risk of fracture. There are many factors that contribute to the development of this condition, including ionizing radiation exposure. Declines in bone volume and trabecular micro-architecture have been found following exposure to multiple types of radiation. Past research has implicated reduction of osteoblast function and changes to vasculature as the primary sources of bone deterioration. Recently, an early increase in osteoclast number was observed following exposure to low-energy X-rays, identifying an increase in resorption as a possible cause and potential target for treatment. The goals of this research are to further characterize the effects of X-rays on trabecular bone at multiple skeletal sites and time points, and assess the effectiveness of the bisphosphonate risedronate to mitigate the radiation-induced deterioration of the trabecular network.
The results from this research indicate trabecular bone deterioration can occur within the first week following exposure to ionizing radiation, with no effects on cortical bone. Serum markers of bone resorption are elevated at 7 days, indicating an early increase in osteoclast activity. Importantly, bisphosphonate administration prevents the deterioration of trabecular bone volume and architecture at all time points and sites, further supporting earlier findings of osteoclast-mediated bone loss.
In order to fully characterize the mechanisms resulting in bone loss, the radiation-induced changes to bone cells should be studied more closely along with effects on bone formation and resorption rates. Earlier time points within the first week post-irradiation must be examined to determine the timeline when changes to bone cells produce functional declines in bone volume and architecture. Additionally, the effects of these declines need to be correlated with changes in overall bone strength in order to determine the most appropriate dosing regimen for preventative and/or treatment therapies. The data from these studies may be useful in determining the most effective method of preventing fractures following radiotherapy.

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