Total-Body Irradiation of Postpubertal Mice with¹³⁷Cs Acutely Compromises the Microarchitecture of Cancellous Bone and Increases Osteoclasts

Abstract

Ionizing radiation can cause substantial tissue degeneration, which may threaten the long-term health of astronauts and radiotherapy patients. To determine whether a single dose of radiation acutely compromises structural integrity in the postpubertal skeleton, 18-week-old male mice were exposed to (137)Cs gamma radiation (1 or 2 Gy). The structure of high-turnover, cancellous bone was analyzed by microcomputed tomography (microCT) 3 or 10 days after irradiation and in basal controls (tissues harvested at the time of irradiation) and age-matched controls. Irradiation (2 Gy) caused a 20% decline in tibial cancellous bone volume fraction (BV/TV) within 3 days and a 43% decline within 10 days, while 1 Gy caused a 28% reduction 10 days later. The BV/TV decrement was due to increased spacing and decreased thickness of trabeculae. Radiation also increased ( approximately 150%) cancellous surfaces lined with tartrate-resistant, acid phosphatase-positive osteoclasts, an index of increased bone resorption. Radiation decreased lumbar vertebral BV/TV 1 month after irradiation, showing the persistence of cancellous bone loss, although mechanical properties in compression were unaffected. In sum, a single dose of gamma radiation rapidly increased osteoclast surface in cancellous tissue and compromised cancellous microarchitecture in the remodeling appendicular and axial skeleton of postpubertal mice.

Mechanical loading causes site-specific anabolic effects on bone following exposure to ionizing radiation

“…Our findings are consistent with previous reports that characterized the functional adaptation to mechanical loading in both the diaphyseal cortical [44,[54][55][56] and cancellous [45,46] compartments in rodents. Radiation exposure did not affect the structure of the cortical compartment in this study, consistent with results of others using gamma, iron, and proton radiation [52,53], and with our previous findings using gamma radiation [28,31].…”

“…Bone volume and microarchitecture of the proximal tibial metaphysis were quantified by microcomputed tomography (6.7 μm pixel size, 3500 ms integration time, 50 kV, Skyscan 1174, Bruker microCT, Kontich, Belgium), as described previously [28]. Briefly, a 1.0 mm-thick region located 0.24 mm distal to the proximal growth plate of the tibia was selected and semi-autonomously contoured to include cancellous tissue.…”

“…At space-relevant total doses (1-2 Gy), ionizing radiation exposure rapidly induces cancellous bone loss in rodents and acutely increases the number of osteoclasts that line cancellous surfaces contributing to skeletal fragility [25][26][27][28], but also may cause persistent damage to stem and progenitor cells for osteoblasts [29,30]. Exposure to low LET ( 137 Cs gamma, 2 Gy) radiation increases osteoclast surface by 46%, increases apoptosis of marrow cells, causes oxidative damage to lipids within mineralized tissue in 4-mo old male C57BL/6 mice, and decreases tibial cancellous bone volume fraction by 16% [31].…”

“…Low LET radiation (such as gamma or X-rays) can lead to an early increase in mineral apposition rate [28], followed by a reduction in mineralizing surface to bone surface in the cancellous compartment and endocortical surface in situ, reduced matrix formation [26,33], and later suppression of bone formation [34]. Total body gamma irradiation at high doses (5-6 Gy) significantly reduces the marrow cell density and stem cell population, which precedes deterioration of trabecular bone quality and quantity [35].…”

Hemorrhage Trauma Increases Radiation-Induced Trabecular Bone Loss and Marrow Cell Depletion in Mice

“…It is well established that long-term consequences of radiation therapy include increased bone loss and incidence of skeletal fracture (9)(10)(11). Even at low doses (1 Gy) significant reductions in bone volume fraction are demonstrated within 10 days postirradiation (12). The predominant bone damage after whole-body gamma irradiation originates from a rapid loss of trabecular bone tissue, demonstrated as reduced trabecular number and connectivity within cancellous bone compartments (13).…”