Page 89 - Effects of radiotherapy and hyperbaric oxygen therapy on oral microcirculation Renee Helmers

IR fraction dose might be necessary in order to induce comparable vascular reactions associated with RT in humans in the present animal model.
The histology of mandibular bone of groups III and IV showed increase
in fibrotic interstitial tissue and loss of vascular structures in bone and soft
tissue compared to the histology of healthy rabbit mandibular bone. Increased
fibrosis in IR tissue was in agreement with other study reports6,8,18,27,39 and was
described as a decrease in vessel lumen space and increase in thickness of the
tunica intima.6,27 Group IV histologically showed small fields of bone necrosis
marked by empty osteocyte lacunae 11 weeks after a single fraction of 30 Gy. Interestingly, another study reported a significant decrease in bone formation
rate and vascular lumen diameter and increase in tunica intima thickness starting
from 14 weeks after irradiation (highest total dose of 23.6 Gy, total follow up 26
weeks) measured by dynamic histomorphometry and histology assessment.27
In their study bone necrosis only followed after surgical intervention post-IR, 4 which might indicate a less severe impact of IR-dose alone when compared
to our findings after a single fraction of 30 Gy. A significant decrease in
osteocytes and increase in empty lacunae (osteocyte death) in the bone of
irradiated rabbit mandibles was correspondingly demonstrated in another
study after administration of a total dose varying between 35 Gy and 45 Gy (in
5 fractions).39 Additionally, an increase of myofibroblasts invading osteocytes
and surrounding sequesters was noted corresponding with the known chronic
fibrotic state associated with RT.8,39 Finally, group IV showed a lack of osteoblast
lining (periosteum), increased resorption by osteoclast activity and decreased vascularization, which is in line with observations describing human ORN
mandibles.6 The absence of periosteum might be the first step preceding soft
tissue ulceration that eventually succumbs to bone necrosis and exposure.
However, bone necrosis and exposure were not observed in our model.
Previous rabbit models studying IR effects in the HN region applied different treatment approaches such as total radiation dose, duration and number of fractions administered and technique of IR (X-ray tube, linear accelerator, cobalt therapy).1,7,16-18,24,26,28,29,38,39 After dosimetry calculation and comparisons with previous investigations a cumulative dose ranging between 22.4 to 32 Gy was chosen for this pilot study with the purpose to select a clinically relevant spectrum of IR therapy approaches. Because cell and tissue turnover occurs 3 times faster in rabbits compared to humans,7,38 emerging and recovery of IR damage may occur at different times. We hypothesized that a minimum period
Onset of late irradiation effects
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