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NASA NTRS2009

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged ~ 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space flight and two dosing regimens: 1) an oral dose of 70 mg of alendronate taken weekly during flight or 2) a single intravenous (IV) dose of 4 mg of zoledronic acid given several weeks before flight. Currently the study is focusing on the oral option because of NASA s safety concerns with the IV-administered drug. The protocol requests 10 male or female crewmembers on ISS flights of 90 days or longer. Controls are 16 previous ISS crewmembers with QCT scans of the hip performed by these same investigators. The primary outcome measure for this study is hip trabecular bone mineral density measured by QCT, but other measures of bone mass are performed including peripheral QCT (pQCT) and dual-energy x-ray absorptiometry. Serum and urinary bone markers and renal stone risk measured before, during, and after flight are included. Postflight data are currently being collected from 2 ISS crewmembers. Two additional crewmembers will return this spring after ~6-month missions. To date no untoward effects have been encountered.

Spector, Elisabeth↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight on Astronaut Health and Performance

INTRODUCTION Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis missions to the Moon and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices that provide both aerobic and resistive capabilities on one platform without including a treadmill. The European Enhanced Exploration Exercise Device [E4D] is one such apparatus. It is critical to validate the efficacy of using exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the effectiveness of using nominal ISS exercise devices for an entire mission compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS Crewmembers are assigned to one of three groups: 1) Controls (n ≥ 40), who partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), cycling on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS), and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who exercise on the CEVIS and ARED only (n = 8); and 3) Active Group 2, who perform aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both Active groups are not permitted to perform treadmill exercise for the entirety of their flight. Health and performance markers, including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and after spaceflight. RESULTS Fifteen subjects (4 Active [CEVIS + ARED], 11 Control) have been recruited. Data collection is ongoing. CONCLUSIONS This study will assess the efficacy of using exploration exercise modalities, including removing the treadmill exercise capability or exclusively using the E4D, compared to the nominal ISS exercise regimen across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions. Supported by the NASA Human Research Program and NASA Exploration Capabilities

A N Varanoske↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

Introduction: Current exercise countermeasures on the International Space Station (ISS), including treadmill running, cycle ergometry, and resistive exercise, are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices that provide both aerobic and resistive training on one platform without including a treadmill, such as the European Enhanced Exploration Exercise Device (E4D). It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. Methods: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40) who will partake in nominal exercise on the ISS, including running on the treadmill with vibration isolation system 2 (T2), ergometry on the cycle ergometer with vibration isolation and stabilization device (CEVIS), and strength training on the advanced resistive exercise device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. Results: Data collection for this study is currently in progress. Conclusions: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

INTRODUCTION: Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices (such as the European Enhanced Exploration Exercise Device [E4D]) that provide both aerobic and resistive training on one platform without including a treadmill. It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40), who will partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), ergometry on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) device, and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. RESULTS: Thirteen subjects (3 Active [CEVIS + ARED], 10 Control) have been recruited for this study. Data collection is currently in progress. CONCLUSIONS: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

INTRODUCTION: Current exercise countermeasures on the International Space Station (ISS) include treadmill running, cycle ergometry, and resistive exercise, which are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices (such as the European Enhanced Exploration Exercise Device [E4D]) that provide both aerobic and resistive training on one platform without including a treadmill. It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. METHODS: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40), who will partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), ergometry on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) device, and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), and blood and urine biochemical markers of bone metabolism will be assessed before, during, and following spaceflight. RESULTS: Thirteen subjects (3 Active [CEVIS + ARED], 10 Control) have been recruited for this study. Data collection is currently in progress. CONCLUSIONS: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRS1992

Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria

We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Regulatory Physiology↗
NASA NTRSDate not supplied

Effects of Replacing Treadmill Running with Alternative Exercise Countermeasures During Long-Duration Spaceflight

Introduction: Current exercise countermeasures on the International Space Station (ISS), including treadmill running, cycle ergometry, and resistive exercise, are used to protect crewmember health and performance during long-duration spaceflight. However, exploration vehicles for Artemis and beyond will have volume and power restrictions, requiring exercise hardware to have a smaller footprint and use fewer resources. Thus, recent efforts have focused on developing exercise devices (such as the European Enhanced Exploration Exercise Device [E4D]) that provide both aerobic and resistive training on one platform without including a treadmill. It is critical to validate the efficacy of exploration-focused exercise modalities to preserve muscle strength, aerobic fitness, bone density, and sensorimotor performance. Thus, the aim of this study is to determine the physiological effects of spaceflight that occur with nominal ISS exercise prescriptions compared to exploration-forward exercise modalities to determine if a treadmill is required to maintain current levels of protection during long-duration missions. Methods: Crewmembers will be assigned to one of three groups: 1) Control Group (n ≥ 40), who will partake in nominal exercise on the ISS, including running on the Treadmill with Vibration Isolation and Stabilization 2 (T2), ergometry on the Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS) device, and strength training on the Advanced Resistive Exercise Device (ARED); 2) Active Group 1, who will partake in CEVIS and ARED exercise only (n = 8); and 3) Active Group 2, who will partake in aerobic and resistive exercise on the E4D only (n = 8). For Active Group 1, nominal aerobic exercise on T2 will be replaced with corresponding exercise on CEVIS. For Active Group 2, a dedicated exercise prescription will be designed to maximize the capabilities of the E4D to include resistive exercise, cycle ergometry, rowing, and rope pulling. Crewmembers in both active groups will not be permitted to perform treadmill exercise. Health and performance markers including bone mineral density (dual-energy x-ray absorptiometry [DXA]), body composition (DXA), cardiovascular fitness (cycle VO2peak), muscle strength and endurance (isometric/isokinetic testing, power endurance testing), sensorimotor performance (sit-to-stand, obstacle course), postural control (computerized dynamic posturography), Results: Eight subjects (2 Active [CEVIS + ARED], 6 Control) have been recruited for this study. Data collection is currently in progress. Conclusions: This study will assess the efficacy of exploration exercise modalities, including the effects of removing the treadmill exercise capability or of exclusively using the E4D, compared to nominal ISS exercise across an entire mission on bone, muscle, aerobic, and sensorimotor health and performance. Findings from this study will help provide a recommendation on whether these exploration exercise modalities can sufficiently protect against physiological deconditioning during spaceflight or whether a treadmill may be required to maintain current levels of protection during future exploration class spaceflight missions.

A.N. Varanoske↗
NASA NTRS2007

Biomedical Results of ISS Expeditions 1-12

A viewgraph presentation on biomedical data from International Space Station (ISS) Expeditions 1-12 is shown. The topics include: 1) ISS Expeditions 1-12; 2) Biomedical Data; 3) Physiological Assessments; 4) Bone Mineral Density; 5) Bone Mineral Density Recovery; 6) Orthostatic Tolerance; 7) Postural Stability Set of Sensory Organ Test 6; 8) Performance Assessment; 9) Aerobic Capacity of the Astronaut Corps; 10) Pre-flight Aerobic Fitness of ISS Astronauts; 11) In-flight and Post-flight Aerobic Capacity of the Astronaut Corps; and 12) ISS Functional Fitness Expeditions 1-12.

Fogarty, Jennifer↗
NASA NTRS2016

Effects of Hindlimb Unloading and 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 underlying mechanisms of spaceflight-induced bone loss and the possible influences of both microgravity and radiation are not fully understood although emerging evidence suggests that these two factors may interact to result in increased bone loss. Previously, gene expression analysis of hair follicles from astronauts, as well as skin from space-flown mice, revealed changes in the expression of genes related to DNA damage and oxidative stress responses. These results resemble the responses of bone to spaceflight-like radiation and simulated weightlessness by hindlimb unloading (HU). Hence in this study, we initiated studies to determine whether skin can be used to predict the responses of bone to simulated microgravity and radiation. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR). To investigate the effects of irradiation andor HU on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated) (CT), hindlimb unloading (HU), 56Fe radiation (IR) and both HU+IR. Animals were euthanized 11 days post-IR, and results were analyzed by 1-way ANOVA. In skin samples, Cdkn1a was decreased to the same extent in HU and HU+IR (47 of CT). In addition, HU reduced FoxO3 expression (46 of CT) and IR increased Gadd45g expression 135 compared CT in skin. But in bone, HU increased FoxO3 expression 31 compared the level of CT. These results suggest that radiation and simulated weightlessness regulated simliar oxidative stress and cell cycle arrest genes in both skin and bone, although the time course and direction of changes may differ. This research may lead to the development of a relatively simple diagnostic tool for bone loss with the advantage that hair follicles and skin are relatively easy to acquire from subjects.

Terada, Masahiro↗
NASA NTRS1975

Evaluation of the effects of hypergravity exposure and caging restraint on bone mineralization in the Beagle by in vivo photon absorptiometry

Photon absorptiometry was used to evaluate bone mineral kinetics associated with normal development and the possible perturbations to bone development resulting from hypergravity exposure over a period of six months in developing Beagles. A series of seven measurements were performed at specific times with the first measurement prior to treatment and subsequent measurements at 2, 5, 9, 14, 20 and 26 weeks from the onset of the experiment. Four groups of six male Beagle pups, ranging in age from 85 to 92 days were studied. Two groups were chronically exposed to hypergravity treatments by centrifugation of 2.0 G (18.0 RPM, 11.7 ft radius) and 2.6 G (18.0 RPM, 19.8 ft radius) for the 26 week period. A third group of six dogs served as a caged control to evaluate possible changes due to confinement in small plexiglass cages similar to those of the centrifuge. Thus this control group was subjected to limited exercise due to caging restraint. The fourth group of animals was housed in open runs to allow exercise without the spatial confinement of the smaller plexiglass cages. Results show highly significant differences in body weight, bone length, increase in bone density of control group relative to other groups, and a decrease in bone mineral content in the two gravity treated groups.

Fisher, G. L.↗
NASA NTRS2008

Mice Drawer System

The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

Cancedda, Ranieri↗
NASA NTRS2002

Skeletal Adaptation to Daily Activity: A Biochemical Perspective

Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Whalen, Robert T.↗
NASA NTRS1997

An overview of the issues: physiological effects of bed rest and restricted physical activity

Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

NASA Program Space Physiology and Countermeasures↗
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↗
NASA NTRS1972

Ultrasonic bone densitometer

Human bone density changes can be determined by a device originally developed for in-flight testing of astronauts' bones during extended space missions. Device is comparable in size, weight and power consumption to portable television set.

Hoop, J. M.↗
NASA NTRS1988

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Morukov, B. V.↗