Ionizing Radiation and Bone Loss: Space Exploration and Clinical Therapy Applications
- 266 Downloads
Damage to normal, nontumor bone tissue following therapeutic irradiation increases the risk of fracture among cancer patients. For example, women treated for various pelvic tumors have been shown to have a greater than 65% increased incidence of hip fracture by 5 years postradiotherapy. Another practical situation in which exposure to ionizing radiation may negatively impact skeletal integrity is during extended spaceflight missions. There is a limited understanding of how spaceflight-relevant doses and types of radiation can influence astronaut bone health, particularly when combined with the significant effects of mechanical unloading experienced in microgravity. Historically, negative effects on osteoblasts have been studied. Radiation exposure has been shown to damage osteoblast precursors. Damage to local vasculature has been observed, ranging from decreased lumen diameter to complete ablation within the irradiated volume, causing a state of hypoxia. These effects result in suppression of bone formation and a general state of low bone turnover. More recently, however, we have demonstrated in preclinical mouse models, a very rapid but transient increase in osteoclast activity after exposure to spaceflight and clinically relevant radiation doses. Combined with long-term suppression of bone formation, this skeletal damage may cause long-term deficits. This review will present a broad set of literature outlining our current set knowledge of both clinical therapy and space exploration exposure to ionizing radiation. Additionally, we will discuss prevention of the initial osteoclast-mediated bone loss, the need to promote normal bone turnover and long-term quality of bone tissue, and our hypothesized molecular mechanisms.
KeywordsOsteoporosis Fracture Ionizing radiation Radiation therapy Spaceflight Microgravity Space radiation Osteoclasts Bone Inflammation
This research is supported by the National Space Biomedical Research Institute through NASA NCC 9-58 (BL01302 TAB; PF01403 JSW), NASA Cooperative Agreements NCC9-79 and NCC9-149 (GAN), and the National Institutes of Health (NIAMS R21AR054889 TAB). Support was also provided by the National Institutes of Health (T32 CA113267 JSW). We want to thank Procter and Gamble Pharmaceuticals for providing an unrestricted grant (TAB JSW) and to the MD/PhD Program at The Pennsylvania State University College of Medicine for partial funding support (SAJL).
- 1.Kondo H, Searby ND, Mojarrab R, Phillips J, Alwood J, Yumoto K, Almeida EA, Limoli CL, Globus RK. Total-body irradiation of postpubertal mice with (137)Cs acutely compromises the microarchitecture of cancellous bone and increases osteoclasts. Radiat Res. 2009;171(3):283–9.PubMedCrossRefGoogle Scholar
- 10.NCRP. Report No. 132—radiation protection guidance for activities in low-earth orbit, in 2000. National Council on Radiation Protection and Measurements Bethesda, MD; 2000.Google Scholar
- 14.Florin TA, Fryer GE, Miyoshi T, Weitzman M, Mertens AC, Hudson MM, Sklar CA, Emmons K, Hinkle A, Whitton J, Stovall M, Robison LL, Oeffinger KC. Physical inactivity in adult survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1356–63.PubMedCrossRefGoogle Scholar
- 17.Overgaard M. Spontaneous radiation-induced rib fractures in breast cancer patients treated with postmastectomy irradiation. A clinical radiobiological analysis of the influence of fraction size and dose-response relationships on late bone damage. Acta Oncol. 1988;27(2):117–22.PubMedCrossRefGoogle Scholar
- 63.Kimble RB, Srivastava S, Ross FP, Matayoshi A, Pacifici R. Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1 and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production. J Biol Chem. 1996;271(46):28890–7.PubMedCrossRefGoogle Scholar