Results for “Bone Loss” — Page 26

NASA NTRSDate not supplied

Temporal Changes in Astronauts’ Muscle and Cardiorespiratory Physiology Before, During and After Spaceflight

Background: NASA’s planned space exploration missions will require astronauts to safely perform extravehicular activity (EVA) and to safely egress vehicles in a variety of landing scenarios. Prolonged exposure to spaceflight can diminish tolerance for physical activity, decrease cardiovascular and sensorimotor function, and cause loss of bone mineral density, and reduced muscle mass and strength. Although exercise can mitigate these spaceflight-induced physiological decrements, little is known regarding the time-course of changes in muscle and aerobic performance during spaceflight. Furthermore, these exercise countermeasures are not fully protective. For example, maximal aerobic capacity (VO2pk), lower body muscle cross-sectional area, and strength decrease by about 10% to 15% after short- (~ 14 days) and long-duration (~ 6 months) missions on the International Space Station (ISS). Future space missions that are longer in duration and further from Earth will employ exploration vehicles that will have exercise hardware with less robust and more constrained exercise capabilities than of those available on the ISS. Thus, countermeasures will need to be optimized to protect crew health and performance on exploration-class missions that will last up to 3 years. This will require a more detailed understanding of the dynamic effects of spaceflight on human health and performance, and the ability of exercise to protect against this deconditioning, and the interaction of exercise with interrelated factors like nutrition, sleep, and environmental conditions. Methods: We will use standardized research and medical testing protocols previously validated in 1-G and 0-G to quantify the time course and the inter-individual variability of changes in physical performance, including cardiorespiratory fitness, and muscle strength, and endurance, before, during and after spaceflight missions lasting 2 months, 6 months, and 1 year. Additionally, we will use an extrapolation model to predict changes associated with 2–3-year exploration missions. Additionally, we will monitor in-flight exercise, nutrition, and sleep using in-flight assessment tools. Significance: Our testing protocols will provide valuable information for determining time course of change and the interindividual variability of spaceflight-induced deconditioning of aerobic capacity and muscle strength and endurance over the course of spaceflight missions up to and beyond 1 year. This information will be vital to assess whether humans can be physically ready for deep space exploration, such as on a mission to Mars, using current technology, or if additional mitigation strategies are necessary.

countermeasures↗

NASA NTRSDate not supplied

Temporal Changes in Astronauts’ Muscle and Cardiorespiratory Physiology Before, During, and After Spaceflight

Background: NASA’s planned space exploration missions will require astronauts to safely perform extravehicular activity (EVA) and to safely egress vehicles in a variety of landing scenarios. Prolonged exposure to spaceflight can diminish tolerance for physical activity, decrease cardiovascular and sensorimotor function, cause loss of bone mineral density, as well as reduced muscle mass and strength. Although exercise can mitigate these spaceflight-induced physiological decrements, little is known regarding the time-course of changes in muscle and aerobic performance during spaceflight. Furthermore, these exercise countermeasures are not fully protective. For example, maximal aerobic capacity (VO2pk), lower body muscle cross-sectional area, and strength decrease by about 10% to 15% after short- (≈14 days) and long-duration (≈6 months) missions on the International Space Station (ISS). Future space missions longer in duration and further from Earth will employ exploration vehicles that will have exercise hardware with less robust and more constrained exercise capabilities than of those available on the ISS. Thus, countermeasures will need to be optimized to protect crew health and performance on exploration-class missions lasting up to 3 years. This requires a more detailed understanding of the dynamic effects of spaceflight on human health and performance, the ability of exercise to protect against this deconditioning, and the interaction of exercise with interrelated factors like nutrition, sleep, and environmental conditions. Methods: We will use standardized research and medical testing protocols previously validated in 1g and microgravity to quantify the time course and the inter-individual variability of changes in physical performance, including cardiorespiratory fitness and muscle strength and endurance, before, during, and after spaceflight missions lasting 2 months, 6 months, and 1 year. Additionally, we will use an extrapolation model to predict changes associated with multi-year exploration missions. Additionally, we will monitor in-flight exercise, nutrition, and sleep using in-flight assessment tools. Significance: Our testing protocols will provide valuable information for determining time course of change and the interindividual variability of spaceflight-induced deconditioning of aerobic capacity and muscle strength and endurance over the course of spaceflight missions up to and beyond 1 year. This information will be vital to assess whether humans can be physically ready for deep space exploration, such as on a mission to Mars, using current technology, or if additional mitigation strategies are necessary.

N Strock↗

NASA NTRSDate not supplied

Temporal Changes in Astronauts’ Muscle and Cardiorespiratory Physiology Before, During, and After Spaceflight

NASA’s planned space exploration missions will require astronauts to safely perform extravehicular activity (EVA) and to safely egress vehicles in a variety of landing scenarios. Prolonged exposure to spaceflight decreases cardiovascular and sensorimotor function, causes loss of bone mineral density, reduces muscle mass and strength, and ultimately diminishes tolerance for physical activity. Although exercise can help mitigate these spaceflight-induced physiological decrements, little is known regarding the time-course of changes in muscle and aerobic performance during spaceflight. Furthermore, these exercise countermeasures are not fully protective. For example, maximal aerobic capacity (VO2pk), lower body muscle cross-sectional area, and strength all decrease by about 10% to 15% after long-duration missions on the International Space Station (ISS). Future long-duration space missions beyond Low Earth Orbit will employ exploration vehicles with less robust exercise hardware and more constrained exercise capabilities (e.g., less operational volume, less active exercise time) than provided on the ISS. Thus, countermeasures will need to be optimized to protect crew health and performance on exploration-class missions lasting up to 3 years. This requires a more detailed understanding of the dynamic effects of spaceflight on human health and performance, the ability of exercise to protect against this deconditioning, and the interaction of exercise with interrelated factors like nutrition, sleep, and environmental conditions.

N.C. Strock↗

NASA NTRSDate not supplied

Long Term Human Presence in Space Requires Artificial Gravity and Radiation Shielding

Astronauts who spend many months in microgravity suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system changes. Exercise countermeasures have been insufficient to maintain normal human performance. Similar problems can be expected in the partial gravity of the Moon and Mars. Achieving the long-term presence of healthy humans in space requires providing artificial Earth level gravity. This can be done on the Moon and Mars by using horizontally rotating habitats with angled floors, but it is easier in space habitats. Astronauts travelling beyond the protection of the Earth’s magnetic field can suffer harm from cosmic background radiation and occasional strong solar flares. Supporting healthy long-term human lives will require radiation shielding on the Moon and Mars as well as in space. Human space settlement will probably begin with artificial rotating space habitats in Low Earth Orbit (LEO) where they will be shielded from radiation. The earlier anticipated human communities in pressurized domes on the Moon or Mars appear unrealistic because of the now known problems of partial gravity and radiation.

Astronauts↗

NASA NTRS2023

Long Term Human Presence in Space Requires Artificial Gravity and Radiation Shielding

Astronauts who spend many months in microgravity suffer serious health problems including muscle atrophy, cardiovascular deconditioning, bone calcium loss, impaired vision, and immune system changes. Exercise countermeasures have been insufficient to maintain normal human performance. Similar problems can be expected in the partial gravity of the Moon and Mars. Achieving the long-term presence of healthy humans in space requires providing artificial Earth level gravity. This can be done on the Moon and Mars by using horizontally rotating habitats with angled floors, but it is easier in space habitats. Astronauts travelling beyond the protection of the Earth’s magnetic field can suffer harm from cosmic background radiation and occasional strong solar flares. Supporting healthy long-term human lives will require radiation shielding on the Moon and Mars as well as in space. Human space settlement will probably begin with artificial rotating space habitats in Low Earth Orbit (LEO) where they will be shielded from radiation. The earlier anticipated human communities in pressurized domes on the Moon or Mars appear unrealistic because of the now known problems of partial gravity and radiation.

Astronauts↗

NASA NTRSDate not supplied

Temporal Changes in Astronauts’ Muscle and Cardiorespiratory Physiology Before, During, and After Spaceflight

NASA’s planned space exploration missions will require astronauts to safely perform extravehicular activity (EVA) and to safely egress vehicles in a variety of landing scenarios. Prolonged exposure to spaceflight decreases cardiovascular and sensorimotor function, causes loss of bone mineral density, reduces muscle mass and strength, and ultimately diminishes tolerance for physical activity. Although exercise can help mitigate these spaceflight-induced physiological decrements, little is known regarding the time-course of changes in muscle and aerobic performance during spaceflight. Furthermore, these exercise countermeasures are not fully protective. For example, maximal aerobic capacity (VO2pk), lower body muscle cross-sectional area, and strength all decrease by about 10% to 15% after long-duration missions on the International Space Station (ISS). Future long-duration space missions beyond Low Earth Orbit will employ exploration vehicles with less robust exercise hardware and more constrained exercise capabilities (e.g., less operational volume, less active exercise time) than provided on the ISS. Thus, countermeasures will need to be optimized to protect crew health and performance on exploration-class missions lasting up to 3 years. This requires a more detailed understanding of the dynamic effects of spaceflight on human health and performance, the ability of exercise to protect against this deconditioning, and the interaction of exercise with interrelated factors like nutrition, sleep, and environmental conditions.

N. Strock↗

NASA NTRS1997

The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

Schwartz, Robert J.↗

NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Spinal Cord Injury↗

NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Risk Surveillance↗

NASA NTRS1985

Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment

Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

Blair, H. C.↗

NASA NTRS2015

Evidence Report: Risk Factor of Inadequate Nutrition

The importance of nutrition in exploration has been documented repeatedly throughout history, where, for example, in the period between Columbus' voyage in 1492 and the invention of the steam engine, scurvy resulted in more sailor deaths than all other causes of death combined. Because nutrients are required for the structure and function of every cell and every system in the body, defining the nutrient requirements for spaceflight and ensuring provision and intake of those nutrients are primary issues for crew health and mission success. Unique aspects of nutrition during space travel include the overarching physiological adaptation to weightlessness, psychological adaptation to extreme and remote environments, and the ability of nutrition and nutrients to serve as countermeasures to ameliorate the negative effects of spaceflight on the human body. Key areas of clinical concern for long-duration spaceflight include loss of body mass (general inadequate food intake), bone and muscle loss, cardiovascular and immune system decrements, increased radiation exposure and oxidative stress, vision and ophthalmic changes, behavior and performance, nutrient supply during extravehicular activity, and general depletion of body nutrient stores because of inadequate food supply, inadequate food intake, increased metabolism, and/or irreversible loss of nutrients. These topics are reviewed herein, based on the current gap structure.

Smith, Scott M.↗

NASA NTRS1974

Bone mineral measurement from Apollo experiment M-078

Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed.

Vogel, J. M.↗

NASA NTRS1980

Computerized tomographic determination of spinal bone mineral content

The aims of the study were three-fold: to determine the magnitude of vertebral cancellous mineral loss in normal subjects during bedrest, to compare this loss with calcium balance and mineral loss in peripheral bones, and to use the vertebral measurements as an evaluative criterion for the C12MDP treatment and compare it with other methods. The methods used are described and the results from 14 subjects are presented.

Cann, C. E.↗

NASA NTRS1987

Skeletal response to simulated weightlessness - A comparison of suspension techniques

Comparisons are made of the skeletal response of rats subjected to simulated weightlessness by back or tail suspension. In comparison to pair-fed control rats, back-suspended rats failed to gain weight whereas tail-suspended rats exhibited normal weight gain. Quantitative bone histomorphometry revealed marked skeletal abnormalities in the proximal tibial metaphysis of back-suspended rats. Loss of trabecular bone mass in these animals was due to a combination of depressed longitudinal bone growth, decreased bone formation, and increased bone resorption. In contrast, the proximal tibia of tail-suspended rats was relatively normal by these histologic criteria. However, a significant reduction trabecular bone volume occurred during 2 weeks of tail suspension, possibly due to a transient inhibition of bone formation. The findings indicate that tail suspension may be a more appropriate model for evaluating the effects of simulated weightlessness on skeletal homeostasis.

Wronski, T. J.↗

NASA NTRS2006

Exploration Health Risks: Probabilistic Risk Assessment

Maintenance of human health on long-duration exploration missions is a primary challenge to mission designers. Indeed, human health risks are currently the largest risk contributors to the risks of evacuation or loss of the crew on long-duration International Space Station missions. We describe a quantitative assessment of the relative probabilities of occurrence of the individual risks to human safety and efficiency during space flight to augment qualitative assessments used in this field to date. Quantitative probabilistic risk assessments will allow program managers to focus resources on those human health risks most likely to occur with undesirable consequences. Truly quantitative assessments are common, even expected, in the engineering and actuarial spheres, but that capability is just emerging in some arenas of life sciences research, such as identifying and minimize the hazards to astronauts during future space exploration missions. Our expectation is that these results can be used to inform NASA mission design trade studies in the near future with the objective of preventing the higher among the human health risks. We identify and discuss statistical techniques to provide this risk quantification based on relevant sets of astronaut biomedical data from short and long duration space flights as well as relevant analog populations. We outline critical assumptions made in the calculations and discuss the rationale for these. Our efforts to date have focussed on quantifying the probabilities of medical risks that are qualitatively perceived as relatively high risks of radiation sickness, cardiac dysrhythmias, medically significant renal stone formation due to increased calcium mobilization, decompression sickness as a result of EVA (extravehicular activity), and bone fracture due to loss of bone mineral density. We present these quantitative probabilities in order-of-magnitude comparison format so that relative risk can be gauged. We address the effects of conservative and nonconservative assumptions on the probability results. We discuss the methods necessary to assess mission risks once exploration mission scenarios are characterized. Preliminary efforts have produced results that are commensurate with earlier qualitative estimates of risk probabilities in this and other operational contexts, indicating that our approach may be usefully applied in support of the development of human health and performance standards for long-duration space exploration missions. This approach will also enable mission-specific probabilistic risk assessments for space exploration missions.

Rhatigan, Jennifer↗

NASA NTRS1987

Histomorphometric analysis of rat skeleton following spaceflight

Male Sprague-Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared with data derived from ground-based control rats. Trabecular bone mass was not altered during the 1st wk of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. For the most part, histological indexes of bone resorption were normal in flight rats. The results indicate that 7 days of weightlessness are not of sufficient duration to induce histologically detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the 1st wk of spaceflight.

Non-NASA Center↗

NASA NTRS1986

Skeletal response to short-term weightlessness

Male Sprague Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared to data derived from ground based control rats. Trabecular bone mass was not altered during the first week of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. Histologic indices of bone resorption was relatively normal in flight rats. The results indicate that 7 day of weightlessness are not of sufficient duration to induce histologicaly detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the first week of space flight.

Wronski, T. J.↗

NASA NTRS2017

Effects of Ionizing Radiation on Murine Gene Expression in Skin and Bone

Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The potential for exposure to space radiation to contribute to lasting decrements in bone mass is not yet understood. Sustained changes to bone mass have a relatively long latency for development, however skin is a radiation sensitive organ and changes in skin gene expression may serve as an early radiation biomarker of exposures and may correlate with adverse effects on skeletal tissue. Previous studies have shown that FGF18 gene expression levels of hair follicles collected from astronauts on the ISS rose over time. In the hair follicle, FGF18 signaling mediates radioresistance in the telogen by arresting the cell cycle, and FGF18 has the potential to function as a radioprotector. In bone, FGF18 appears to regulate cell proliferation and differentiation positively during osteogenesis and negatively during chondrogenesis. Cellular defense responses to radiation are shared by a variety of organs, hence in this study, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We have examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (TBI). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and TBI (0.5 Gy Fe-56 600 MeV/n and 0.5 Gy H-1 150 MeV/n). Animals were euthanized one and 11 days post-IR. Statistical analysis was performed via a Student's ttest. In skin samples one day after IR, skin expression of FGF18 was significantly greater (3.8X) than sham-irradiated controls (3.8X), but did not differ 11 days post TBI. Expression levels of other radiation related genes (Nfe2l2, Trp53, Cdkn1a, FoxO3, Gadd45g, SOD1), was not different due to TBI at either time point. In bone (femora) TBI significantly increased (3.8X) expression of the pro-bone resorption cytokine, MCP-1, one day after TBI. FGF18 expression in skin and MCP- 1 expression in bone were found to be positively correlated (P less than 0.002, r=0.8779). Further, microcomputed tomography analysis of tibae from these animals showed reduced fractional cancellous bone volume (-21.7%) at 11 days post exposure. These results suggest that early radiation induced changes in FGF18 gene expression in skin may have value for predicting subsequent loss of cancellous bone mass.

space radiation↗