Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss.
The present study investigated the detrimental effects of non-lethal, high-dose (whole body) γ-irradiation on bone, and the impact that radiation combined with skin trauma (i.e. combined injury) has on long-term skeletal tissue health. Recovery of bone after an acute dose of radiation (RI; 8 Gy), skin wounding (15-20% of total body skin surface), or combined injury (RI+Wound; CI) was determined 3, 7, 30, and 120 days post-irradiation in female B6D2F1 mice and compared to non-irradiated mice (SHAM) at each time-point. CI mice demonstrated long-term (day 120) elevations in serum TRAP 5b (osteoclast number) and sclerostin (bone formation inhibitor), and suppression of osteocalcin levels through 30 days as compared to SHAM (p<0.05). Radiation-induced reductions in distal femur trabecular bone volume fraction and trabecular number through 120 days post-exposure were significantly greater than non-irradiated mice (p<0.05) and were exacerbated in CI mice by day 30 (p<0.05). Negative alterations in trabecular bone microarchitecture were coupled with extended reductions in cancellous bone formation rate in both RI and CI mice as compared to Sham (p<0.05). Increased osteoclast surface in CI animals was observed for 3 days after irradiation and remained elevated through 120 days (p<0.01). These results demonstrate a long-term, exacerbated response of bone to radiation when coupled with non-lethal wound trauma. Changes in cancellous bone after combined trauma were derived from extended reductions in osteoblast-driven bone formation and increases in osteoclast activity.
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA; Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA. Electronic address: joshua.m.swift.mil@mail.mil.
Joshua M
JM
Swift
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA; Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA. Electronic address: sibyl.swift@fda.hhs.gov.
Sibyl N
SN
Swift
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA. Electronic address: joan.smith@usuhs.edu.
Joan T
JT
Smith
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA. Electronic address: juliann.kiang@usuhs.edu.
Juliann G
JG
Kiang
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202 USA. Electronic address: matallen@iupui.edu.
Matthew R
MR
Allen
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects*; D006023:Glycoproteins / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010006:Osteoblasts / Q000000981:diagnostic imaging / Q000528:radiation effects*; D010010:Osteoclasts / Q000166:cytology; D010012:Osteogenesis; D000069079:Radiation Exposure; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology* / Q000528:radiation effects*; D013314:Stress, Mechanical; D014945:Wound Healing; D055114:X-Ray Microtomography
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse
Bone biomarkers; Bone marrow; Combined trauma; Murine; Osteoclast; Trabecular