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NASA NTRS2018

Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bed rest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Schepelmann, Alexander↗
NASA NTRS2019

Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Schepelmann, Alexander↗
NASA NTRS2007

ECP Bone Workshop Day 2, Session 1: Validation of Exercise Countermeasures

The thesis of this session of the ECP Bone workshop is that computer modeling is required in order to evaluate factor of risk for fracture when considering the uniquely localized bone loss conditions experienced by Astronauts. This session provides an opportunity to introduce the Integrated Medical Model Bone Fracture Risk (IMM-BFxRM) simulation approach and how this and other models improve understanding of the effects of exercise countermeasures. This workshop session also provides an opportunity for the panel to provide recommendations on this and other "complex modeling" approaches, as well as, the importance of funding the IMM-BFxRM and companion efforts by external scientists (Lang and Keyak).

Myers, Jerry G.↗
NASA NTRS2015

High Intensity Resistive and Rowing Exercise Countermeasures Do Not Prevent Orthostatic Intolerance Following 70 Days of Bed Rest

More than 60% of US astronauts participating in Mir and early International Space Station missions (greater than 5 months) were unable to complete a 10‐min 80 deg head‐up tilt test on landing day. This high incidence of post‐spaceflight orthostatic intolerance may be related to limitations of the inflight exercise hardware that prevented high intensity training. PURPOSE: This study sought to determine if a countermeasure program that included intense lower‐body resistive and rowing exercises designed to prevent cardiovascular and musculoskeletal deconditioning during 70 days of 6 deg head-down tilt bed rest (BR), a spaceflight analog, also would protect against post‐ BR orthostatic intolerance. METHODS: Sixteen males participated in this study and performed no exercise (Control, n=10) or performed an intense supine exercise protocol with resistive and aerobic components (Exercise, n=6). On 3 days/week, exercise subjects performed lower body resistive exercise and a 30‐min continuous bout of rowing (greater than or equal to 75% max heart rate). On 3 other days/week, subjects performed only high‐intensity, interval‐style rowing. Orthostatic intolerance was assessed using a 15‐min 80 deg head‐up tilt test performed 2 days (BR‐2) before and on the last day of BR (BR70). Plasma volume was measured using a carbon monoxide rebreathing technique on BR‐3 and before rising on the first recovery day (BR+0). RESULTS: Following 70 days of BR, tilt tolerance time decreased significantly in both the Control (BR‐2: 15.0 +/- 0.0, BR70: 9.9 +/- 4.6 min, mean +/- SD) and Exercise (BR‐2: 12.2 +/- 4.7, BR70: 4.9 +/- 1.9 min) subjects, but the decreased tilt tolerance time was not different between groups (Control: ‐34 +/- 31, Exercise: ‐56 +/- 16%). Plasma volume also decreased (Control: ‐0.56 +/- 0.40, Exercise: ‐0.48 +/- 0.33 L) from pre to post‐BR, with no differences between groups (Control: ‐18 +/- 11%, Exerciser: ‐15 +/-1 0%). CONCLUSIONS: These findings confirm previous reports in shorter BR studies that the performance of an exercise countermeasure protocol by itself during BR does not prevent orthostatic intolerance or plasma volume loss. This suggests that protection against orthostatic intolerance in astronauts following long‐duration spaceflight will require an additional intervention, such as periodic orthostatic stress, fluid repletion, and/or lower‐body compression garments.

Lee, Stuart M. C.↗
NASA NTRS2001

Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

Smith, Scott M.↗
NASA NTRS2006

WISE-2005: LBNP/Treadmill and Resistive Exercise Countermeasures Maintain Aerobic Capacity during a 60-d Bed Rest

We have previously documented that supine treadmill exercise within lower body negative pressure (LBNPex) performed 6 sessions (raised dot) wk(sup -1) during 15- and 30-day bed rests (BR) maintained upright aerobic capacity (VO2pk). In the present study, ure are evaluating whether aerobic capacity is maintained during a 60-d BR when the LBNPex frequency is reduced to 2-4 sessions (raised dot) wk(sup -1) and resistance exercise (REX) is added 2-3 sessions (raised dot) wk(sup -1). Eight healthy women (32 plus or minus 4 yrs; 56.4 plus or minus 3.6 kg; 164 plus or minus 8 cm; mean plus or minus SD) performed maximal-exertion, graded treadmill tests before and 3 days after a 60-d, 6 deg. head-down tilt BR. (Earliest day the medical monitors would permit a maximal exercise test post-BR). During BR, four subjects performed no exercise (CON), while four other subjects (EX) performed LBNPex and REX on separate days. The LBNPex countermeasure employed an intermittent (40-80% pre-BR VO2pk), 40-min protocol against an LBNP pressure (-49 plus or minus 3 mmHg) applied to provide a footward force equivalent to 1.0-1.2 body weight. REX consisted of maximal concentric and eccentric supine leg press and heel raise exercises using a gravity-independent flywheel ergometer. Comparisons were performed using paired (within-group) or non-paired (between-group) t-tests. Three days post-BR, VO2pk of the CON group was reduced significantly from pre-BR (Pre:37.2 plus or minus 1.2, Post: 29.4 plus or minus 2 ml (raised dot) kg(sup -1) (raised dot) min(sup -1), P less than 0.05), while the VO2pk of the EX group was not significantly reduced (Pre: 39.6 plus or minus 1.9, Post: 38.0 plus or minus 0.6 ml (raised dot) kg(sup -1) (raised dot) min(sup -1)). Peak heart rate, ventilation, rating of perceived exertion, and respiratory exchange ratio were not significantly different between the two groups pre- and post-BR. These preliminary results suggest that the combined LBNPex and REX countermeasures may be sufficient to maintain upright aerobic capacity after long-duration space flights.

Schneider, Suzanne M.↗
NASA NTRS2008

Lower Body Negative Pressure Treadmill Exercise and Resistive Exercise Countermeasures Maintain Physiologic Function in Women during Simulated Microgravity

We hypothesized that supine LBNP treadmill exercise combined with Flywheel resistive exercise maintains upright physiologic responses following 60-days of head-down tilt (HDT) bed rest (BR). METHODS: 16 healthy women (age 25-40 years) underwent 60-days HDT (-6deg.) BR. Women were assigned to either a non-exercise control group (CON, n=8) or to an exercise group (EX, n=8). EX subjects performed a 40-min, variable intensity LBNP exercise protocol at foot-ward forces between 1.0-1.1 times body weight, followed by 10- min of resting LBNP 3-4 days/week. Resistive exercise of maximal concentric and eccentric supine leg press and heel raise exercises were performed using a flywheel ergometer 2-3 days/week. IRBs approved this study with informed/written consent. RESULTS: Post-BR VO2pk was not different in EX (-3.3+/-1.2%) but decreased significantly in CON (-21.2+/-2.1%), p< 0.05. Post-BR orthostatic tolerance time (mean se) decreased significantly less in EX (19.3+/-1.3 to 14.4+/-1.5 min) than in CON (17.5+/-0.1 to 9.1+/- 1.5 min), p=0.03. Post-BR muscle strength decreased significantly in CON, but was preserved in EX. Post-BR bone resorption was greater than pre-BR in both groups (p<0.05). Bone formation markers, were significantly elevated (p<0.05) in EX than in CON. CONCLUSIONS: Supine LBNP treadmill exercise along with flywheel resistive exercise maintains upright exercise capacity, orthostatic responses and muscle strength during 60-days HDT BR.

Macias, B. R.↗
NASA NTRS1989

Exercise countermeasures for bed rest deconditioning

The major objectives were to evaluate the efficiency of different modes of exercise (isotonic and isokinetic) for countering the effects of bed rest deconditioning on work capacity (peak oxygen uptake), muscular strength, orthostatic tolerance, posture, equilibrium and gait; and to collect additional data of a more fundamental nature to help understand how these deconditioning responses occur. These data will be used for writing prescriptions for exercise to be utilized by astronauts for maintaining work capacity and well-being on Freedom Station, and to determine what exercise devices should be place in the station.

Greenleaf, John↗
NASA NTRS1987

P-31 Magnetic Resonance Spectroscopy (MRS) of limb muscles during bedrest with exercise countermeasures

Nineteen volunteers in bed with head down tilt (-6 deg) for 1 month and doing or not exercise training while in bed (lido or ergometer) had their limb muscle studied by magnetic resonance spectroscopy. A protocol of repetitive exercise in the magnet was set and a wooden probe designed to support the limb and to allow exercise. Spectra were recorded continuously during the protocol. In each spectrum, inorganic phosphate, phosphocreatin, adenosin triphosphate, and pH were measured. All the subjects were studied before, after bedrest, and 6 weeks later. After 1 month, the lido group show no changes in the spectra of their leg muscles while the group doing no exercise or ergometer do. For the arms, a loss of muscle function is only seen in the group doing no exercise.

Berry, P.↗
NASA NTRS1999

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and their Implications for Bone Strain

Effective countermeasures to prevent loss of bone mineral during long duration space flight remain elusive. Despite an exercise program on MIR flights, the data from LeBlanc et al. (1996) indicated that there was still a mean rate of loss of bone mineral density in the proximal femur of 1.58% per month (n=18, flight duration 4 - 14.4 months). The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. A plausible hypothesis is that bone loss during space flight, such as that reported by LeBlanc et al. (1996), may result from failure to effectively load the skeleton in order to generate localized bone strains of sufficient magnitude to prevent disuse osteoporosis. A variety of methods have been proposed to simulate locomotor exercise in reduced gravity. In such simulations, and in an actual microgravity environment, a gravity replacement load (GRL) must always be added to return the exercising subject to the support surface and the resulting skeletal load is critically dependent upon the magnitude of the GRL. To our knowledge, GRLs during orbital flight have only been measured once (on STS 81) and it is likely that most or all prior treadmill exercise in space has used GRLs that were less than one body weight. McCrory (1997) has shown that subjects walking and running in simulated zero-G can tolerate GRLs of 1 if an appropriate harness is used. Several investigators have attempted to measure in vivo strains and forces in the bones of humans, but have faced ethical and technical limitations. The anteromedial aspect of the tibial midshaft has been a common site for the placement of strain gauges; one reason to measure strains in the anterior tibia is that this region is surgically accessible. Aamodt et al. (1997) were able to measure strains on the lateral surface of the proximal femur only because their experimental subjects were already scheduled for hip surgery. Lu et al. (1997) used an instrumented massive proximal femoral prosthesis along with electromyographic measurements to demonstrate that femoral forces depend on muscular activity. These analyses of in vivo bone mechanics are valuable. The invasive nature of the procedures involved, however, limits both the number of subjects and the number of strain gauge locations. Further, the results of these studies may be confounded by the inclusion of subjects with pathological conditions. Gross et al. (1992) measured strain at three locations on the equine third metacarpal and used those data to construct a computer model of the internal strain environment of the bone. An analogous placement of multiple gauges in living humans would be difficult and potentially hazardous because of the depth of soft tissue overlying the tibia and femur.

Peterman, M.↗
NASA NTRS1993

Exercise countermeasures for bed-rest deconditioning

The purpose for this 30-day bed rest study was to investigate the effects of short-term, high intensity isotonic and isokinetic exercise training on maintenance of working capacity (peak oxygen uptake), muscular strength and endurance, and on orthostatic tolerance, posture and gait. Other data were collected on muscle atrophy, bone mineralization and density, endocrine analyses concerning vasoactivity and fluid-electrolyte balance, muscle intermediary metabolism, and on performance and mood of the subjects. It was concluded that: The subjects maintained a relatively stable mood, high morale, and high esprit de corps throughout the study. Performance improved in nearly all tests in almost all the subjects. Isotonic training, as opposed to isokinetic exercise training, was associated more with decreasing levels of psychological tension, concentration, and motivation; and improvement in the quality of sleep. Working capacity (peak oxygen uptake) was maintained during bed rest with isotonic exercise training; it was not maintained with isokinetic or no exercise training. In general, there was no significant decrease in strength or endurance of arm or leg muscles during bed rest, in spite of some reduction in muscle size (atrophy) of some leg muscles. There was no effect of isotonic exercise training on orthostasis, since tilt-table tolerance was reduced similarly in all three groups following bed rest. Bed rest resulted in significant decreases of postural stability and self-selected step length, stride length, and walking velocity, which were not influenced by either exercise training regimen. Most pre-bed rest responses were restored by the fourth day of recovery.

Greenleaf, John↗
NASA NTRS1991

Neuromuscular aspects in development of exercise countermeasures

The paper reviews data obtained at the Human Life Sciences Research Program at the Kennedy Space Center on the structural and functional characteristics of the human muscle and on the effects of simulated microgravity (head-down bed rest) and exercise on the muscle. It is shown that prolonged exposure to microgravity induced ultrastructural abnormalities and the atrophy of muscle and impaired muscle functioning (especially upon return to terrestrial gravity) and that ground-based models can be effectively used to study these changes. Results indicate that the incorporation of resistive exercise with a strong emphasis on the use of eccentric muscle action, in addition to concentric action, may provide a very effective countermeasure against muscle atrophy and dysfunction caused by long-duration exposures to microgravity.

Convertino, Victor A.↗
NASA NTRS1999

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and Their Implications for Bone Strain

The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

Peterman, M.↗
NASA NTRS1996

Fibre Size and Capillary Supply in Human M.vastus Lateralis after Long-Duration Spaceflight: Effects of Countermeasure Exercise Training

Muscle fiber atrophy is shown to be induced in human m.vastus lateralis even during short duration spaceflight. A study carried out to evaluate the effects of long duration spaceflight on human skeletal muscle fiber characteristics is reported on. Muscle fiber size and capillary supply were measured in samples obtained from the m.vastus lateralis of astronauts before and after a long duration flight. Most of the astronauts performed more than 80 percent of the recommended exercise training loads in terms of volume and intensity. Very slight fiber changes were found in fiber size and muscle capillary supply indices. It is concluded that the main factor which maintained fiber characteristics in the astronauts was the exercise measures taken by them.

Shenkman, Boris S.↗
NASA NTRS2009

NASA Exercise Physiology and Countermeasures Project Overview

Efficient exercise countermeasures are necessary to offset or minimize spaceflight-induced deconditioning and to maximize crew performance of mission tasks. These countermeasure protocols should use the fewest crew and vehicle resources. NASA s Exercise Physiology and Countermeasures (ExPC) Project works to identify, collect, interpret, and summarize evidence that results in effective exercise countermeasure protocols which protect crew health and performance during International Space Station (ISS) and future exploration-class missions. The ExPC and NASA s Human Research Program are sponsoring multiple studies to evaluate and improve the efficacy of spaceflight exercise countermeasures. First, the Project will measure maximal aerobic capacity (VO2max) during cycle ergometry before, during, and after ISS missions. Second, the Project is sponsoring an evaluation of a new prototype harness that offers improved comfort and increased loading during treadmill operations. Third, the Functional Tasks Test protocol will map performance of anticipated lunar mission tasks with physiologic systems before and after short and long-duration spaceflight, to target system contributions and the tailoring of exercise protocols to maximize performance. In addition to these studies that are actively enrolling crewmember participants, the ExPC is planning new studies that include an evaluation of a higher-intensity/lower-volume exercise countermeasure protocol aboard the ISS using the Advanced Resistive Exercise Device and second-generation treadmill, studies that evaluate bone loading during spaceflight exercise, and ground-based studies that focus on fitness for duty standards required to complete lunar mission tasks and for which exercise protocols need to protect. Summaries of these current and future studies and strategies will be provided to international colleagues for knowledge sharing and possible collaboration.

Loerch, Linda↗