Abstract
BackgroundBone-related complications are commonly reported in cancer patients receiving radiotherapy and are collectively referred to as the abscopal effect of irradiation, the mechanism of which remains poorly understood. When patients receive targeted radiotherapy to a tumor, the local skeleton is exposed to radiation, particularly within the bone marrow. We therefore investigated the hypothesis that single bone irradiation can induce deterioration of the skeleton outside the radiation field and is mediated by the bone marrow.MethodsUsing 4-month-old male Sprague-Dawley rats, the effects of irradiation (20 Gy, right distal femur and proximal tibia) on bone quality, microarchitecture and bone marrow, were evaluated prospectively by microcomputed tomography, histomorphometry, real-time polymerase chain reaction, and Western blot analysis.ResultsAt 12 weeks post-irradiation, bone loss of the non-irradiated bone was induced and marrow adiposity was increased. Expression of runt-related transcription factor-2 by bone mesenchymal stem cells (BMSCs) decreased after irradiation by 88.0 % (P < 0.01) at the contralateral and 82.3 % (P < 0.01) at the irradiation site 2 weeks post-irradiation and decreased by 94.5 % (P < 0.001) at the contralateral and 44.1 % (P < 0.05) at the irradiation site 12 weeks post-irradiation. Interestingly, peroxisome proliferator-activated receptor gamma expression decreased by 61.8 % (P < 0.05) at the contralateral and by 48.3 % (P < 0.05) at the irradiation site 2 weeks post-irradiation but increased by 9-fold at the contralateral (P < 0.001) and by 13-fold (P < 0.001) at the irradiation site 12 weeks post-irradiation.ConclusionsThese data highlight that radiation-induced bone complications are partly BMSC-mediated, with important implications for bone health maintenance in patients receiving radiotherapy.
Highlights
Bone-related complications are commonly reported in cancer patients receiving radiotherapy and are collectively referred to as the abscopal effect of irradiation, the mechanism of which remains poorly understood
Twelve weeks post-irradiation (20 Gy), trabecula bone mineral density (BMD) of the femur was reduced by 18.1 % (P < 0.05) at the contralateral femur and by 21.2 % (P < 0.05) at the irradiated femur relative to control (Fig. 1a, b); trabecular bone volume fraction (BV/TV) was reduced by 23.2 % (P < 0.05) at the contralateral femur and by 30.8 % (P < 0.05) at the irradiated femur relative to the control femur (Fig. 1d)
The ratio of bone surface to the bone volume (BS/BV) was increased by 20.4 % (P < 0.05) at the contralateral femur and by 32.9 % (P < 0.05) at the irradiated femur compared to the control group (Fig. 1c)
Summary
Bone-related complications are commonly reported in cancer patients receiving radiotherapy and are collectively referred to as the abscopal effect of irradiation, the mechanism of which remains poorly understood. The frequently reported skeletal complications after local irradiation include regional and systemic osteopenia, osteoporosis, osteonecrosis, and non-malignancy fracture, all of which can seriously reduce the life quality of cancer survivors [9, 10] Diagnosis of these skeletal complications is often prompted by patient pain at the affected bones. The median time for a fracture diagnosis is between 6 and 16.9 months for female patients treated with radiotherapy for pelvic malignancies when acute syndrome of irradiation is not observed [9, 11, 12] During this prolonged time after irradiation, the mechanisms by which accumulated changes in the bone occur without irradiation exposure are not clear and appear to be multifactorial.
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