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Abstract
Stem cell depletion and compromised bone marrow resulting from radiation exposure fosters long term deterioration of numerous physiologic systems, with the degradation of the skeletal system ultimately increasing the risk of fractures. To analyze the effects of radiation on the bone marrow and bone architecture, young (8wk old) and skeletally mature (16wk old) C57BL/6 mice were irradiated with sub-lethal doses of γ-irradiation, and their bone marrow and bone structure were assessed over time and compared to age-matched controls. At 2d following 5Gy of irradiation, 8wk and 16wk old mice underwent a -65% and -63% deficit to their bone marrow total cell populations, respectively. No sign of recovery was visible in the total cell numbers at 10d. After 8w, the mature mice still had -12% fewer bone marrow cells compared to the age-matched control. Interestingly, the majority of bone loss in the tibiae following irradiation was abrupt, occurring within 10d of exposure. The 8wk and 16wk old mice experienced -41% and -39% declines in their trabecular bone volume fractions respectively, which remained -45% and -51% lower at 8w. This period of bone architectural destruction aligned with a deficit to the bone marrow cell populations. It is difficult to understand though how the bone architecture experienced severe devastation if the cells responsible for bone turnover were depleted. We hypothesized that both a physicochemical and a biological response contributed to the destruction of the bone architecture. Fourier transform infrared imaging was used to assess trabecular bone chemical composition in the young mice, and it showed a -4.3% declining trend in tissue mineralization at 2d, decreasing to -5.8% by 10d compared to control. This suggests that a physicochemical process from gamma rays contributed to architectural destruction because 2d is an insufficient period for cell mediated bone destruction. The results within this dissertation detail the devastation of irradiation on the bone marrow and architecture, as well as the need to inhibit bone loss.
