BACKGROUND: Radioprotective modalities such as dose fractionation and 
pharmacologic agents such as amifostine have been used to protect bone and other 
types of normal tissue from the damaging effects of ionizing radiation without 
significantly impacting tumor kill. To better understand the cellular mechanism 
of radioprotection of osseous tissue, the authors sought to determine the effect 
of dose fractionation and amifostine on isolated osteoblasts.
METHODS: Isolated primary rat calvarial osteoblasts were exposed to single or 
fractionated doses of ionizing radiation both with and without amifostine 
pretreatment. Endpoints included cell growth (n = 4), vascular endothelial 
growth factor production as measured by enzyme-linked immunosorbent assay (n = 
3), and early osteodifferentiation as measured by a quantitative alkaline 
phosphatase assay (n = 3).
RESULTS: Both dose fractionation and amifostine protect osteoblasts from the 
growth inhibitory effects of ionizing radiation. Fractionation but not 
amifostine was protective for hypoxia-induced vascular endothelial growth factor 
production (used as a surrogate marker of normal osteoblast function). Neither 
fractionation nor amifostine could prevent the inhibitory effect of ionizing 
radiation on normal osteoblast osteodifferentiation as measured by alkaline 
phosphatase production.
CONCLUSIONS: Both dose fractionation and amifostine have valid roles as 
radioprotectants for osteoblasts and can act in an additive fashion. 
Radioprotection of cell growth and viability does not necessarily correlate with 
preservation of normal cellular function. Combination protocols involving dose 
fractionation and amifostine may be effective in radioprotection of osteoblasts 
and normal osseous tissue.