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NASA NTRS1990

Experiment K-6-01. Distribution and biochemistry of mineral and matrix in the femurs of rats

Previous analyses of the composition of mineral and matrix in the bone of young rats following space flight has revealed deficits in calcium, phosphorus, and osteocalcin, a non-collagenous protein, without an associated decrease in collagen. To characterize the location and nature of this mineralization defect in a weight bearing long bone, the femur, researchers attempted to relate the spatial distribution of mineral in situ in the proximal, central and distal thirds of the femoral diaphysis to the biochemical composition of bone from the same area. Biochemical analyses revealed lower concentrations of calcium, phosphorus and osteocalcin but not collagen only in the central third of the diaphysis of the flight animals (F) compared to synchronous controls (S). Collagen concentration was reduced only in the proximal third of the diaphysis, where all 3 crosslinks, expressed as nM/mol collagen were higher in F than S. A new technique, x ray microtomography, with a resolution of 26 microns, was used to obtain semi-quantitative data on mineral distribution in reconstructed sections of wet whole bone. To improve the resolution of the mineral density distribution, images of the surfaces of cut sections were analyzed by backscattered electrons in a scanning electron microscope (BSE). There was good agreement between the results of the two stereochemical techniques which revealed distinct patterns of mineralization in transverse and longitudinal directions of the diaphysis. The novel methodology developed for this flight experiment shows considerable promise in elucidating the biochemical nature of what appear to be regional alterations in the mineralization of long bones of animals exposed to spaceflight.

Arnaud, S.↗

NASA NTRS1990

Experiment K-6-23. Effect of spaceflight on levels and function of immune cells

Two different immunology experiments were performed on samples received from rats flown on Cosmos 1887. In the first experiment, rat bone marrow cells were examined in Moscow for their response to colony stimulating factor-M. In the second experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States where they were subjected to analysis on a flow cytometer. The results of the studies indicate that bone marrow cells from flown rats showed a decreased response to colony stimulating factor than did bone marrow cells from control rats. There was a higher percentage of spleen cells from flown rats staining positively for pan-T-cell, suppressor-T-cell and innate interleukin-2 receptor antigens than from control animals. In addition, a higher percentage of cells that appeared to be part of the myelogenous population of bone marrow cells from flown rats stained positively for surface immunoglobulin than did equivalent cells from control rats.

Mandel, A. D.↗

NASA NTRS1989

Changes in mineral metabolism with immobilization/space flight

Researchers are still unsure of the accuracy of previous bone density measurements of their significance following a period of weightlessness. Rapid technological advances in the measurement of bone density will enable us now to measure bone density accurately at multiple sites in the skeleton with doses of radiation less than that given by a spine x ray. It may not be possible to obtain this type of information before the next series of space flights take place, although the bed-rest model may provide supporting information. Extensive testing of bone density on every astronaut should be performed before and after the space flight. Prevention and treatment can only be undertaken after gathering sufficient baseline information. The use of exercise in preventing bone loss is still highly speculative, but represents a relatively easy approach to the problem in terms of study.

Gallagher, J. C.↗

NASA NTRS1993

The Design of Mechanically Compatible Fasteners for Human Mandible Reconstruction

Mechanically compatible fasteners for use with thin or weakened bone sections in the human mandible are being developed to help reduce large strain discontinuities across the bone/implant interface. Materials being considered for these fasteners are a polyetherertherketone (PEEK) resin with continuous quartz or carbon fiber for the screw. The screws were designed to have a shear strength equivalent to that of compact/trabecular bone and to be used with a conventional nut, nut plate, or an expandable shank/blind nut made of a ceramic filled polymer. Physical and finite element models of the mandible were developed in order to help select the best material fastener design. The models replicate the softer inner core of trabecular bone and the hard outer shell of compact bone. The inner core of the physical model consisted of an expanding foam and the hard outer shell consisted of ceramic particles in an epoxy matrix. This model has some of the cutting and drilling attributes of bone and may be appropriate as an educational tool for surgeons and medical students. The finite element model was exercised to establish boundary conditions consistent with the stress profiles associated with mandible bite forces and muscle loads. Work is continuing to compare stress/strain profiles of a reconstructed mandible with the results from the finite element model. When optimized, these design and fastening techniques may be applicable, not only to other skeletal structures, but to any composite structure.

Roberts, Jack C.↗

NASA NTRS1995

The Effects of Rm-CSF and Ril-6 Therapy on Immunosuppressed Antiorthostatically Suspended Mice

Antiorthostatically suspended mice had suppressed macrophage development in both unloaded and loaded bones, indicating a systemic effect. Bone marrow cells from those mice secreted less macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) than did control mice. Because M-CSF and IL-6 are important to bone marrow macrophage maturation, we formulated the hypothesis that suppressed macrophage development occurred as a result of the depressed levels of either M-CSF or IL-6. To test the hypothesis, mice were administered recombinant M-CSF or IL-6 intraperitoneally. We showed that recombinant M-CSF therapy, but not recombinant IL-6 therapy, reversed the suppressive effects of orthostatic suspension on macrophage development. These data suggest that bone marrow cells that produce M-CSF are affected by antiorthostatic suspension and may contribute to the inhibited maturation of bone marrow macrophage progenitors.

Armstong, Jason W.↗

NASA NTRS1994

Experiment K-7-23: Effect of Spaceflight on Level and Function of Immune Cells: Immunology Studies - Part 1

Two different experiments were carried out in this segment of the immunology protocol for samples received from rats flown on Cosmos 2044. Control groups included vivarium, synchronous and antiorthostatically suspended rats. In the first experiment, rat bone marrow cells were examined in Moscow for their response to recombinant murine colony stimulating factor-granulocyte / monocyte (CSF-GM). In the second experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. The results of the studies indicated that bone marrow cells from flown and suspended rats showed a decreased response to CSF-GM as compared to bone marrow cells from control rats. Spleen cells from flown rats showed increased percentages of suppressor-cytotoxic-T and helper-T cells amongst the entire cell population. Bone marrow cells showed an increase in the percentage of helper-T cells in the myelogenous population and increased percentages of anti-asialo GM-1 bearing, interleukin-2 receptor bearing, pan-T and helper-T cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. These results are similar, but not identical to, earlier results from Cosmos 1887, and confirm that space flight can have profound effects on immune system components and activities.

Sonnenfeld, G.↗

NASA NTRS1999

Gravity and Skeletal Growth

Two simultaneous experiments were performed using 5-week-old male Sprague Dawley rats; in one study, the rats were flown in low earth orbit; in the other study, the hindlimbs of the growing rats were elevated to prevent weight bearing. Following 9 d of unloading, weight bearing was restored for 4, 28, and 76 hrs. Afterwards, additional hindlimb unloading experiments were performed to evaluate the skeletal response to 0, 2, 4, 6, 8, 10, 12, 16, and 24 hrs of restored weight bearing following 7 d of unloading. Cancellous and cortical bone histomorphometry were evaluated in the left tibia at the proximal metaphysis and in the left femur at mid-diaphysis, respectively. Steady-state mRNA levels for bone matrix proteins and skeletal signaling peptides were determined in total cellular RNA extracted from trabeculae from the right proximal tibiametaphysis and periosteum from the right femur. Spaceflight and hindlimb unloading each resulted in cancellous osteopenia, as well as a tendency towards decreased periosteal bone formation. Both models for skeletal unloading resulted in site specific reductions in mRNA levels for transforming growth factor-beta (sub 1) (TGF-beta) osteocalcin (OC), and prepro-alpha (I) subunit of type 1 collagen (collagen) and little or no changes in mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAP) and insulin-like growth factor I (IGF-I). Restoration of normal weight bearing resulted in transient increases in mRNA levels for the bone matrix proteins and TGF-beta in the proximal metaphysis and periosteum and no changes in either GAP or IGF-I mRNA levels. The timecourse for the response differed between the two skeletal compartments; the tibial metaphysis responded much more quickly to reloading. These results suggest that the skeletal adaptation to acute physiological changes in mechanical usage are mediated, in part, by changes in mRNA levels for bone matrix proteins and TGF-beta.

Morey-Holton, Emily↗

NASA NTRS1994

Vitamin D Status in Monkey Candidates for Space Flight

In preparation for the Cosmos 2229 Biosatellite space flight experiments in Rhesus monkeys, we evaluated the status of vitamin D in animals of different origins: candidates for space flight raised in Moscow (IMBP) and animals housed at Ames Research Ctr. (ARC) for pilot studies. Diets at IMBP were natural foods found by analysis to contain 1.4% Ca, 2.8% P and<240 IU D3/kg and at ARC standard monkey chow with 0.9% Ca, 0.5% P and 6600 IU D3/kg. We measured body weights (BW), serum calcium (TCa), total protein (TP), phosphorus (Pi), alkaline phosphatase (AP), 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) in 16 IMBP and 15 ARC male animals and indices of bone formation in cancellous bone obtained from iliac crest biopsy of 6 IMBP and 13 ARC animals. BW were the same in juveniles at IMBP as ARC although ARC monkeys were born a year later. Mean(1SD) TCa and TP were higher and 25D lower (1819 vs. 93+18 ng/ml,p<.001) in IMBP than ARC animals. 1,25D (174156 vs. 212+77 pg/ml), Pi and AP were similar. In bone, osteoid and osteoblast surfaces averaged 38114% and 33+15% in all, with %vol. of osteoid higher in IMBP than ARC monkeys of the same BW (p<.05) Indices of bone formation were inversely related to 25D, not 1,25D. Of interest are similar 1,25D levels associated with a wide range of substrate and extensive osteoid in bone of D replete animals.

Arnaud, S. B.↗

NASA NTRS1994

Quantification of Cyclic Ground Reaction Force Histories During Daily Activity in Humans

Theoretical models and experimental studies of bone remodeling suggest that bone density and structure are influenced by local cyclic skeletal tissue stress and strain histories. Estimation of long-term loading histories in humans is usually achieved by assessment of physical activity level by questionnaires, logbooks, and pedometers, since the majority of lower limb cyclic loading occurs during walking and running. These methods provide some indication of the mechanical loading history, but fail to consider the true magnitude of the lower limb skeletal forces generated by various daily activities. These techniques cannot account for individual gait characteristics, gait speed, and unpredictable high loading events that may influence bone mass significantly. We have developed portable instrumentation to measure and record the vertical component of the ground reaction force (GRFz) during normal daily activity. This equipment allows long-term quantitative monitoring of musculoskeletal loads, which in conjunction with bone mineral density assessments, promises to elucidate the relationship between skeletal stresses and bone remodeling.

Breit, G. A.↗

NASA NTRS2004

Ethnic Differences in Bending Stiffness of the Ulna and Tibia

There is considerable information about the variations in bone mass associated with different opportunity to compare a mechanical property of bone in young college women of Caucasian, Hispanic and Asian descent who gave informed consent to participate in an exercise study. The subjects were sedentary, in good health, eumenorrheic, non-smokers and had body mass indices (BMI) less than 30. Measurements acquired were body weight, kg, and height, cm, calcaneal and wrist bone density, g/square cm (PIXI, Lunar GE) and bending stiffness (EI, Nm(exp 2)) in the ulna and tibia. E1 was determined non-invasively with an instrument called the Mechanical Response Tissue Analyzer (MRTA) that delivers a vibratory stimulus to the center of the ulna or tibia and analyzes the response curve based on the equation E1 = k(sub b) L(exp 3)/48 where k, is lateral bending stiffness, L is the length of the bone, E is Young's modulus of elasticity and I, the bending moment of inertia. The error of the test (CV) based on measurements of an aluminum rod with a known E1 was 4.8%, of calcaneal BMD, 0.54%, and of wrist bone density, 3.45%.

Arnaud, S. B.↗

NASA NTRS2003

Dual reporter transgene driven by 2.3Col1a1 promoter is active in differentiated osteoblasts

AIM: As quantitative and spatial analyses of promoter reporter constructs are not easily performed in intact bone, we designed a reporter gene specific to bone, which could be analyzed both visually and quantitatively by using chloramphenicol acetyltransferase (CAT) and a cyan version of green fluorescent protein (GFPcyan), driven by a 2.3-kb fragment of the rat collagen promoter (Col2.3). METHODS: The construct Col2.3CATiresGFPcyan was used for generating transgenic mice. Quantitative measurement of promoter activity was performed by CAT analysis of different tissues derived from transgenic animals; localization was performed by visualized GFP in frozen bone sections. To assess transgene expression during in vitro differentiation, marrow stromal cell and neonatal calvarial osteoblast cultures were analyzed for CAT and GFP activity. RESULTS: In mice, CAT activity was detected in the calvaria, long bone, teeth, and tendon, whereas histology showed that GFP expression was limited to osteoblasts and osteocytes. In cell culture, increased activity of CAT correlated with increased differentiation, and GFP activity was restricted to mineralized nodules. CONCLUSION: The concept of a dual reporter allows a simultaneous visual and quantitative analysis of transgene activity in bone.

Non-NASA Center↗

NASA NTRS1998

Effects of microgravity on osteoblast growth

Studies from space flights over the past two decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. Recently analyzed data from the 1973-1974 Skylabs disclose that there is a rise in the systemic hormone, cortisol, which may play a role in bone loss in flight. In two flights where bone growth was measured (Skylabs 3 and 4), the crew members had a significant loss of calcium accompanied by a rise in 24 hour urinary cortisol during the entire flight period. In ground-based work on osteoblasts, we have demonstrated that equivalent amounts of glucocorticoids can inhibit osteoblast cell growth. In addition, this laboratory has recently studied gene growth and activation of mouse osteoblasts (MC3T3-E1) during spaceflight. Osteoblast cells were grown on glass coverslips, loaded in the Biorack plunger boxes 18 hours before launch and activated 19 hours after launch in the Biorack incubator under microgravity conditions. The osteoblasts were launched in a serum deprived state, activated and collected in microgravity. Samples were collected at 29 hours after sera activation (0-g, n=4; 1-g, n=4). The osteoblasts were examined for changes in gene expression and cell morphology. Approximately one day after growth activation, remarkable differences were observed in gene expression in 0-g and 1-g flight samples. The 0-g activated cells had increased c-fos mRNA when compared to flight 1-g controls. The message of immediate early growth gene, cox-2 was decreased in the microgravity activated cells when compared to ground or 1-g flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of actin mRNA between the 0-g and 1-g samples. These data indicate that quiescent osteoblasts are slower to enter the cell cycle in microgravity, suggesting that the force of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-g. Here we examine ground-based and space flown data on osteoblast growth in ground-based experiments mimicking space flight conditions and in microgravity to simulate lack of gravity stress to help us understand the mechanism of bone loss by experiments.

NASA Experiment Number 9403056↗

NASA NTRS1999

Preparing for Mars: the physiologic and medical challenges

As the twentieth century closes, retrospectives cite the Apollo moon missions as one of the important events of the past 100 years. A trip to Mars, however, would be even more challenging and significant. A round-trip Mars journey would require nearly three years away from Earth, a significant leap in complexity compared to the two week long Moon trips or the record-breaking fourteen-month flight on Mir. What would be the physiologic and medical challenges of a Mars flight? Two key areas of physiology present the greatest potential problems--calcium metabolism and radiation exposure. Data from Mir missions show that bone loss continues in space despite an aggressive countermeasure program. Average losses were 0.35% per month, but some load bearing areas lost >1% per month. A 1% loss rate, if it continued unabated for 30 months, could produce osteoporosis. Smaller losses could still increase fracture risk. Some bone loss can be well tolerated, particularly if the bone can be regained after the mission. But the effectiveness of post-flight rehabilitation to restore the density and quality of bone after spaceflight is not well known. Bone loss estimates are based on continuous weightlessness exposure, but this is not a requirement for a Mars trip. Most of the time on a Mars trip will be spent in the 1/3 Earth's gravity environment on Mars, and either intermittent or continuous artificial gravity can be provided for the transit between planets (although at an engineering cost). The dosing of the gravity exposure (e.g. the level and duration), however, has not been established. Radiation protection also requires a balance between engineering cost and human health. Excessive shielding could add billions of dollars to the cost of a mission. Trips in interplanetary space, however, expose the crew to heavy high-energy particles from cosmic rays (HZE particles), which have a high linear energy transfer. This high energy leads to significant biological damage (e.g. chromosomal aberrations, cancer induction). A recent report from the Committee on Space Biology and Medicine notes that only one systematic study of cancer induction from high-energy particles has been conducted (using the mouse Harderian gland). Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data. Other areas of physiology also present problems, such as muscle loss, cardiovascular deconditioning, and vestibular adaptation. Despite all the issues, however, a focussed, aggressive research program that uses the resources of the International Space Station should pave the way for mankind's greatest adventure--a trip to Mars.

STS-90 Shuttle Project↗

NASA NTRS1998

Extracellular calcium (Ca2+o)-sensing receptor in a mouse monocyte-macrophage cell line (J774): potential mediator of the actions of Ca2+o on the function of J774 cells

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone remodeling and may play a role in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for bone marrow mononuclear cells in the vicinity, leading us to investigate whether such mononuclear cells express the CaR. In this study, we used the mouse J774 cell line, which exhibits a pure monocyte-macrophage phenotype. Both immunocytochemistry and Western blot analysis, using polyclonal antisera specific for the CaR, detected CaR protein in J774 cells. The use of reverse transcriptase-polymerase chain reaction with CaR-specific primers, including a set of intron-spanning primers, followed by nucleotide sequencing of the amplified products, also identified CaR transcripts in J774 cells. Exposure of J774 cells to high Ca2+o (2.8 mM or more) or the polycationic CaR agonist, neomycin (100 microM), stimulated both chemotaxis and DNA synthesis in J774 cells. Therefore, taken together, our data strongly suggest that the monocyte-macrophage cell line, J774, possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney.

NASA Discipline Musculoskeletal↗

NASA NTRS2007

Nutritional Status Assessment (SMO 016E)

It has not been possible to assess nutritional status of crew members on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in nutritional status for several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. SMO 016E is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment parameters will be expanded to include parameters that will allow us to better understand changes in folate and vitamin B6 status, and related cardiovascular risk factors during and after flight. Additionally, stress hormones and hormones that affect bone and muscle metabolism will also be measured. This additional assessment will allow us to better monitor the health of crew members and make more accurate recommendations for their rehabilitation. Several nutritional assessment parameters are altered at landing, but it is not known how long these changes persist. We extended the current protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how nutritional status and related systems are affected by space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.

Smith, S. M.↗

NASA NTRS2006

Development of the Gecko (Pachydactylus turneri) Animal Model during Foton M-2 to Study Comparative Effects of Microgravity in Terrestrial and Aquatic Organisms

Terrestrial organisms exposed to microgravity during spaceflight experience degeneration in bone, muscle, and possibly other tissues that require gravity-mediated mechanical stimulation for normal regenerative growth. In the Gecko experiment aboard Foton M-2, we flew for the first time, five terrestrial Pachydactylus turneri specimens to develop a model of microgravity effects comparable to the newt Pleurodeles waltl, a well-established model organism for spaceflight. These lower vertebrate species have similar body plans and size, are poikilothermic, have tissue regenerative ability, and are adapted to moderate periods of fasting. Furthermore the gecko (Pachydactylus) can also survive prolonged periods without water. In pre-flight control experiments and after a 16-day Foton M-2 spaceflight without food or water, the geckos were recovered and showed no apparent negative health effects. However, detailed analysis of bone mass and architecture by micro Computed Tomography { pCT), showed that both synchronous control and spaceflight animals lost significant amounts of cancellous bone in the distal femur and humerus relative to basal controls. In addition, cell cycle analysis of 30h post-flight liver tissue reveals a shift of DNA content from G2 and S to G1, both in spaceflight and synchronous controls. Together, these results suggest that housing conditions alone induce rapid catabolism of cancellous bone and reduced normal tissue regeneration. Further use of the gecko Puchydactylus turneri as a spaceflight model requires modification of housing conditions, possibly by including water and food, or changing other factors such as eliminating housing stresses to obtain stable bone structure and tissue regeneration during spaceflight experiments.

Almeida, E. A.↗

NASA NTRS2009

Nutritional Status Assessment (SMO 016E)

Until 2006, it was not been possible to assess nutritional status of crewmembers on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in status of several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. Collecting samples during flight is one of the objectives of SMO 016E, and it is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment variables will be expanded to include ones that will allow us to better understand changes in folate, vitamin K, and vitamin B6 status, as well as risk factors for cardiovascular and oxidative damage during and after flight. Stress hormones and hormones that affect bone and muscle metabolism will also be measured. Measuring these additional variables will allow us to better monitor the health of crewmembers and make more accurate recommendations for their rehabilitation. Several nutritional assessment variables are altered at landing, but it is not known how long these changes persist. We extended the original protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how nutritional status and related systems are affected by space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.

Smith, S. M.↗

NASA NTRS2008

Forecasting Proximal Femur and Wrist Fracture Caused by a Fall to the Side during Space Exploration Missions to the Moon and Mars

The possibility of bone fracture in space is a concern due to the negative impact it could have on a mission. The Bone Fracture Risk Module (BFxRM) developed at the NASA Glenn Research Center is a statistical simulation that quantifies the probability of bone fracture at specific skeletal locations for particular activities or events during space exploration missions. This paper reports fracture probability predictions for the proximal femur and wrist resulting from a fall to the side during an extravehicular activity (EVA) on specific days of lunar and Martian exploration missions. The risk of fracture at the proximal femur on any given day of the mission is small and fairly constant, although it is slightly greater towards the end of the mission, due to a reduction in proximal femur bone mineral density (BMD). The risk of wrist fracture is greater than the risk of hip fracture and there is an increased risk on Mars since it has a higher gravitational environment than the moon. The BFxRM can be used to help manage the risk of bone fracture in space as an engineering tool that is used during mission operation and resource planning.

Lewandowski, Beth E.↗