Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model

Abstract

Abstract. radiotherapy is successfully used to treat neoplastic lesions, but may adversely affect normal tissues within the irradiated volume. however, additional clinical and para-clinical data are required for a comprehensive understanding of the pathogenesis of this damage. We assessed a rat model using clinical records and medical imaging to gain a better understanding of irradiation-induced tissue damage. the hindlimbs of the rats in this model were irradiated with a single dose of 30 or 50 Gy. Sequential analysis was based on observation records of stage and planar scintigraphy. additional radiography, radiohistology and histology studies were performed to detect histological alterations. all animals developed acute and late effects, with an increased severity after a dose of 50 Gy. the bone uptake of 99m Tc-HDP was significantly decreased in a dose-and time-dependent manner. Histologically, significant tissue damage was observed. after the 50 Gy irradiation, the animals developed lesions characteristic of osteoradionecrosis (Orn). radiographic and histological studies provided evidence of lytic bone lesions. Our rat model developed tissue damage characteristic of radiation injury after a single 30 Gy irradiation and tissue degeneration similar to that which occurs during human Orn after a 50 Gy irradiation. the development of this animal model is an essential step in exploring the pathogenesis of irradiation-induced tissue damage, and may be used to test the efficacy of new treatments. Introductionradiotherapy is successfully used to treat regional neoplastic lesions, but may have an adverse effect on normal tissues. irradiated tissue abnormalities include the impairment of vascularization (1-3) due to the high vulnerability of small vascular endothelial cells, impairment of cell homeostasis with cellular apoptosis (3-6), and the accumulation of fibrosis (5,7). Bone tissue is very vulnerable to irradiation (8,9) and undergoes impaired healing, infection, atrophy, pathological fractures and bone tissue necrosis, termed osteoradionecrosis (Orn), within the irradiated region. these iatrogenic delayed complications occur in various anatomic sites, including the pelvis, sternum, vertebrae, clavicle, femoral head and, in particular, the mandible. the most devastating radiotherapyinduced complications of the head and the neck occur in the mandible, and in some cases require surgical resection (10). the reported incidence of Orn following conventional radiotherapy (rt) to the mandible ranges between 0.9 and 35% (11), with an increased risk at doses exceeding 60 Gy (12).due to the increased use of radiation therapy alone or in combination with chemotherapy in the treatment of head and neck malignancies (13,14), it is likely that the number of radio-induced complications will rise (14-16).despite increased interest in the clinical development of ORN along with a new proposed definition and classification (17), most animal model studies on Orn date from the 1960-70s (18-20). Since then, imaging techniques have evolv...

Protective Effects of Cerium Oxide Nanoparticles on MC3T3-E1 Osteoblastic Cells Exposed to X-Ray Irradiation

“…In addition, radiation therapy in cancer patients may also lead to irradiating damages to normal tissues [1]. For example, studies have shown that high dose of ionizing irradiation can lead to osteoradionecrosis, loss of bone mass and bone fracture [3,4,33]. Therefore, developing effective radio-protectants is more valuable.…”

“…For example, exposure to high-dose ionizing irradiation can cause deleterious effects on bone tissue, and osteoradionecrosis is often seen in cancer patients treated with ionizing irradiation [1,2]. In addition, other serious bone complications, including loss of bone mass, bone fracture and sclerosis, have been reported [3,4]. Increased osteoblastic damage appears to play an important role in the reduced bone mineral density following irradiation [5].…”

The Effect of Perioperative Radiation Therapy on Spinal Bone Fusion Following Spine Tumor Surgery

“…Long after acute phase, radiation-induced osteonecrosis and the dense hypovascular scar left in the radiation bed may leave a poor biologic environment for fusion20). It is well known that high-dose irradiation delivers deleterious effects to bone tissue, including osteoradionecrosis, sclerosis, loss of bone, and bone fracture, in a dose- and time-dependent manner171824). Emery et al6) reported that long bone fractures after irradiation in laboratory animals are associated with a high pseudarthrosis rate, delayed union, decreased strength and decreased periosteal osteoblastic proliferation, decreased formation of cartilage and osteoid, and decreased vascularity after irradiation.…”

“…Typically, in the patients who underwent interbody fusion perioperative irradiation is known to interfere with bone fusion and to make pseudoarthrosis causing a late fracture after surgery710). The abnormalities observed in the irradiated tissue include the impairment of vascularization due to the high vulnerability of small vascular endothelial cells, impairment of cell homeostasis with cellular apoptosis, and the accumulation of fibrosis18). It is well known that high-dose irradiation delivers deleterious effects to bone tissue, including osteoradionecrosis, sclerosis, loss of bone mass, and bone fracture, in a dose- and time-dependent manner21).…”

Effect of low‐dose X‐ray irradiation and Ti particles on the osseointegration of prosthetic

“…It is well known that high-dose irradiation delivers deleterious effects to bone tissue, including osteoradio-necrosis, sclerosis, loss of bone mass, and bone fracture, in a dose-and time-dependent manner. [6][7][8][9] However, the effects of low-dose irradiation on bone responses have rarely been described. Several studies have revealed the detrimental effects of low-dose irradiation (<1 Gy) with various molecular mechanisms, including increases in the generation of reactive oxygen species, DNA double-strand breaks, and chromosomal breakage.…”