Exposure to Low-Dose X-Ray Radiation Alters Bone Progenitor Cells and Bone Microarchitecture

Exposure to high-dose ionizing radiation during medical treatment exerts well-documented deleterious effects on bone health, reducing bone density and contributing to bone growth retardation in young patients and spontaneous fracture in postmenopausal women. However, the majority of human radiation exposures occur in a much lower dose range than that used in the radiation oncology clinic. Furthermore, very few studies have examined the effects of low-dose ionizing radiation on bone integrity and results have been inconsistent. In this study, mice were irradiated with a total-body dose of 0.17, 0.5 or 1 Gy to quantify the early (day 3 postirradiation) and delayed (day 21 postirradiation) effects of radiation on bone microarchitecture and bone marrow stromal cells (BMSCs). Female BALBc mice (4 months old) were divided into four groups: irradiated (0.17, 0.5 and 1 Gy) and sham-irradiated controls (0 Gy). Micro-computed tomography analysis of distal femur trabecular bone from animals at day 21 after exposure to 1 Gy of X-ray radiation revealed a 21% smaller bone volume (BV/TV), 22% decrease in trabecular numbers (Tb.N) and 9% greater trabecular separation (Tb.Sp) compared to sham-irradiated controls (P < 0.05). We evaluated the differentiation capacity of bone marrow stromal cells harvested at days 3 and 21 postirradiation into osteoblast and adipocyte cells. Osteoblast and adipocyte differentiation was decreased when cells were harvested at day 3 postirradiation but enhanced in cells isolated at day 21 postirradiation, suggesting a compensatory recovery process. Osteoclast differentiation was increased in 1 Gy irradiated BMSCs harvested at day 3 postirradiation, but not in those harvested at day 21 postirradiation, compared to controls. This study provides evidence of an early, radiation-induced decrease in osteoblast activity and numbers, as well as a later recovery effect after exposure to 1 Gy of X-rays, whereas osteoclastogenesis was enhanced. A better understanding of the effects of radiation on osteoprogenitor cell populations could lead to more effective therapeutic interventions that protect bone integrity for individuals exposed to low-dose ionizing radiation.