BACKGROUND: The authors have previously demonstrated that amifostine prophylaxis mitigates the pernicious effects of radiation in settings of fracture repair and distraction osteogenesis. Expanding on these studies, the authors examined the biomechanical properties of uninjured bone exposed to both radiation and amifostine. The authors hypothesize that radiation will degrade the biomechanical properties of native bone, and further hypothesize that prophylactic amifostine will preserve biomechanical properties to levels of normal bone and protect against radiation-induced morbidities. METHODS: Rats were randomized into control, irradiated, and amifostine pretreatment plus radiation (amifostine-pretreated) groups. Irradiated animals received a fractionated dosing schedule of 35 Gy, with amifostine-pretreated animals receiving amifostine before irradiation. Hemimandibles were harvested at 8 and 18 weeks for biomechanical testing and micro-computed tomographic analysis. RESULTS: At 8 weeks, irradiated specimens displayed elevations above controls for all biomechanical properties. At 18 weeks, the biomechanical properties of irradiated specimens degraded in comparison with controls; at both time points, amifostine-pretreated specimens were maintained at levels comparable to controls. There was a significant decrease in tissue mineral density from 8- to 18-week irradiated specimens, whereas no such change existed for control and amifostine-pretreated specimens. CONCLUSIONS: The authors' findings demonstrate paradoxical and transient elevations in the initial biomechanical properties of irradiated specimens that were not sustained through the later study time point. Amifostine pretreatment, however, provided uninterrupted preservation of the biomechanical properties of normal, native bone at both time points. This supports the contention that amifostine is capable of providing continuous protection to bone against the untoward effects of radiation therapy.
BACKGROUND: The authors have previously demonstrated that amifostine prophylaxis mitigates the pernicious effects of radiation in settings of fracture repair and distraction osteogenesis. Expanding on these studies, the authors examined the biomechanical properties of uninjured bone exposed to both radiation and amifostine. The authors hypothesize that radiation will degrade the biomechanical properties of native bone, and further hypothesize that prophylactic amifostine will preserve biomechanical properties to levels of normal bone and protect against radiation-induced morbidities. METHODS:Rats were randomized into control, irradiated, and amifostine pretreatment plus radiation (amifostine-pretreated) groups. Irradiated animals received a fractionated dosing schedule of 35 Gy, with amifostine-pretreated animals receiving amifostine before irradiation. Hemimandibles were harvested at 8 and 18 weeks for biomechanical testing and micro-computed tomographic analysis. RESULTS: At 8 weeks, irradiated specimens displayed elevations above controls for all biomechanical properties. At 18 weeks, the biomechanical properties of irradiated specimens degraded in comparison with controls; at both time points, amifostine-pretreated specimens were maintained at levels comparable to controls. There was a significant decrease in tissue mineral density from 8- to 18-week irradiated specimens, whereas no such change existed for control and amifostine-pretreated specimens. CONCLUSIONS: The authors' findings demonstrate paradoxical and transient elevations in the initial biomechanical properties of irradiated specimens that were not sustained through the later study time point. Amifostine pretreatment, however, provided uninterrupted preservation of the biomechanical properties of normal, native bone at both time points. This supports the contention that amifostine is capable of providing continuous protection to bone against the untoward effects of radiation therapy.
Authors: Kavitha Ranganathan; Eric Simon; Jeremy Lynn; Alicia Snider; Yu Zhang; Noah Nelson; Alexis Donneys; Jose Rodriguez; Lauren Buchman; Dawn Reyna; Elke Lipka; Steven R Buchman Journal: Pharm Res Date: 2018-03-19 Impact factor: 4.200