Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation

Abstract

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Knee and Hip Joint Cartilage Damage from Combined Spaceflight Hazards of Low-Dose Radiation Less than 1 Gy and Prolonged Hindlimb Unloading

“…Increased S100A6 concentration with combined HLU and radiation, suggestive of elevated oxidative stress within cartilage (30)(31)(32)(33); and 2. Decreased CPNY2 concentration with all treatments, suggestive of increased apoptosis of chondrocytes vs. necrotic death (34)(35)(36). Increased oxidative stress has been previously shown to promote apoptosis of chondrocytes and an osteoarthritic phenotype (37).…”

Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity

“…For both skeletally mature and immature animals, the resulting cortical thickness maps showed a significant infield cortical thickness loss at the first imaging time point, 2 months post RT [61]. After the initial infield cortical thickness decrease, the effect did not continue to decrease, but rather remained persistently lowered from baseline until the final CT scan at 8 months post RT.…”

“…Micro-CT also improves upon the evaluation of trabecular volume/number and cortical thickness, but is limited to small regions of interest. A novel three-dimensional (3D) cortical mapping algorithm was developed that could easily be scalable to larger CT scans, multiple bones simultaneously, and provide both quantitative and qualitative information on RT-induced bone changes [4,61,62].…”

“…In the creation of this algorithm, the entire vertebral column of 16 rhesus macaques nonhuman primates (NHPs) were assessed before and after these animals had received whole chest irradiation to 10 Gy to the midplane in a single fraction, delivered with 6-MV X-rays in an Anterior-Posterior / Posterior-Anterior (AP/PA) fashion at a dose rate of 6 Gy/min [61]. All NHPs had full body CT scans at 2 months prior to RT, then post RT at 2, 4, 6, and 8 months.…”

Detection and quantification of renal fibrosis by computerized tomography

“…Twenty-two animals (20 male, 2 female) were included in this study, 10 NHP (9 male, 1 female) that had received 5 to 8 Gy total body irradiation 6.4 to 12 years previously, 2 age matched non-irradiated controls (1 male, 1 female), and 10 male NHPs that received 10 Gy chest only irradiation; they had minimal renal radiation exposure. These ten have been analyzed for other studies [8]. As reported therein, the kidneys of chest-only-irradiated NHP received between 1% and 5% of the intended 10 Gy dose, or between 0.1 and 0.5 Gy.…”