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Running head: ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 1
Estimation and Mitigation of Bone Density Loss on a Mission...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 2
Abstract
Prolonged space habitation can cause several musculoskeletal dis...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 3
Introduction
Many years ago, Buzz Aldrin and Neil Armstrong took mankind’...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 4
Prolonged space habitation can cause several musculoskeletal disorders in...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 5
Because all of the physiological processes in the body are dependent on e...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 6
Prolonged stress also affects successful bone remodeling. It is known tha...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 7
therefore, to release large amounts of calcium into the extracellular flu...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 8
Several simulations on muscle mass and bone density loss were conducted t...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 9
bone loss is an estimated 17.2%, giving an upper and lower range of 8.6%-...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 10
Extra-vehicular activity is known to be physically demanding, and while ...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 11
Exercise is currently used as a countermeasure to reduce the effects of ...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 12
Studies have shown that exercise performed on a vibrating platform incre...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 13
Rather than addressing each individual system in a piecemeal fashion, wh...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 14
Reducing cortisol has multiple effects, such as positively influencing b...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 15
References
Astrobiology: The Living Universe. (2000). Countermeasures Ag...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 16
Hsu, J. (2010). New Artificial Gravity Tests in Space Could Help Astrona...
ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 17
Shier D., Butler, J., Lewis, R. (2002). Hole’s Human Anatomy & Physiolog...
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Estimating Bone Loss on a Mars Mission

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Estimating Bone Loss on a Mars Mission

  1. 1. Running head: ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 1 Estimation and Mitigation of Bone Density Loss on a Mission to Mars Amber R. Berlin 2012
  2. 2. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 2 Abstract Prolonged space habitation can cause several musculoskeletal disorders in astronauts. Due to the extended duration of interplanetary travel, more effective mitigation techniques are necessary to reduce the bone loss effects of microgravity. On a mission to Mars, bone density loss estimates indicate astronauts could lose as much as 53.2% of their bone density upon return to Earth. Nutrition and exercise have proven ineffective in mitigating bone loss. Because of the delicate balance of homeostasis, there is not a simple solution to resolve this phenomenon. Lower body massage is hypothesized to address many of the physiological symptoms of microgravity. The effects of massage in a gravitational environment include localized increased blood volume, reduced cortisol production, reduced muscle atrophy, increased function of the endocrine system, and reduced muscle fatigue, all of which are symptoms of microgravity. Studies are needed to assess the effectiveness of massage in a space environment. Low-level vibration has been shown to increase bone density in animal studies, and more research and testing is needed on human subjects. Artificial gravity remains the most promising comprehensive solution to the effects of microgravity, and short-radius centrifuge research will be a top priority for interplanetary missions.
  3. 3. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 3 Introduction Many years ago, Buzz Aldrin and Neil Armstrong took mankind’s first tentative steps on the moon, in what is considered one of the greatest achievements in history. Now, with the retirement of NASA’s Shuttle program and the commercialization of the space industry, there are many more options for space vehicles that would allow interplanetary travel. Competition among leaders in the industry ensures the best technology at the lowest cost, and government funding in promising programs gives the space industry a boost out of its infancy. After all, we have our sights set on Mars. The extreme environment of space creates both mental and physical challenges for our astronauts, and microgravity is known to be a primary hazard of space flight. The human body experiences drastic physiological changes for the duration of exposure to a space environment. The National Space and Biomedical Research Institute (NSBRI) conducts various on-going studies onboard the International Space Station (ISS) to determine the extent of cardiovascular, musculoskeletal, and other physiological changes caused by microgravity. Because of the duration of interplanetary travel to Mars, astronauts will experience a level of microgravity exposure not previously realized. Before we embark on interplanetary travel, we must be assured that our people have the best chance possible to achieve the mission and safely return to Earth. With the current mitigation techniques available, the physiological effects of microgravity will hamper the ability to complete mission critical tasks. In seeking out an adequate solution, we must first understand the delicate balance of homeostasis, the human body’s reaction to a microgravity environment, and the potential of artificial gravity as a comprehensive solution to these physiological effects. Microgravity Affects Homeostasis and Bone Metabolism
  4. 4. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 4 Prolonged space habitation can cause several musculoskeletal disorders in astronauts. One such disorder, bone density loss, can require a long rehabilitation period. “Bone loss is one of the two biggest health risks (radiation exposure is the other) that astronauts face” (Beattie-Moss, 2011). Although exercise programs on Earth have proven to reduce the amount of bone density loss in individuals with osteoporosis, which is similar to the bone loss experienced in microgravity, they have proven inadequate for the mitigation of bone loss in space. A primary reason for bone density loss is the skeletal unloading produced by a lack of gravity. In a gravitational environment, certain bones experience continuous stress, and muscles constantly work against gravitational forces. In microgravity, it is the weight-bearing bones of the body which experience the greatest reduction in bone density. Under gravity, as we travel down the body, each section above adds increased weight to the lower sections, with maximum weight being supported by the feet. The bones experiencing the most drastic changes in density are the calcaneus and talus bones of the heel, the metatarsals and phalange around the ball of the foot, the femur, fibula, and tibia bones of the legs, the pelvic girdle, and the lumbar region of the spine (Markham, 2012). The human body is in a continuous cycle of bone metabolism, which includes ”the cellular removal of old bone, followed by the formation of a new bone matrix, which fills in the precise location of the old bone removal, and subsequently becomes mineralized” (Markham, 2012). The bone is dissolved and reformed by osteoclasts and osteoblasts in a coupled sequence of resorption, reversal and formation. During resorption “osteoclasts digest old bone”, followed by reversal, where “mononuclear cells appear on the bone surface”, and finally formation, where “osteoblasts lay down new bone until resorbed bone is completely replaced” (Hadjidakis and Androulakis, 2006).
  5. 5. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 5 Because all of the physiological processes in the body are dependent on each other, effects experienced in any part of the system results in changes to the entire system. The increase in blood volume in the head and chest, which is a result of the space-normal condition of microgravity, causes a chain reaction that resonates through each individual system as the body tries to maintain homeostasis. The surplus of fluid perceived by this increase has a cascading effect, limiting pancreatic function, which in turn reduces the amount of insulin produced by the pancreas, and causes diabetic-like effects for the duration of the spaceflight (Tobin, Uchakin, and Leeper-Woodford, 2002). Reduced insulin levels inhibit the stimulation of the osteoblastic production of collagen, a process required by bone metabolism (Stipanuk, 2000). Additionally, the reduced blood volume in the lower body during exposure to microgravity further confounds the process of normal bone remodeling. Decreased fluid pressure in the lower extremities is a known contributor to bone density loss. A study by Naslund, Naslund, Lundeberg, Lindberg, and Lund revealed that “blood supply is shown critical for bone metabolism, growth, and fracture healing” (2011). Certain nutrients are also required for bone metabolism, and affect the remodeling process both directly and indirectly. The composition of bone includes organic matter composed of collagen and various proteins. Biochemical research by Stipanuk indicates that “collagen is used as a scaffolding for the deposit of minerals…vitamin D acts to maintain the plasma calcium and phosphate concentrations so that skeletal mineralization occurs… calcitonin lowers blood calcium levels by inhibiting osteoclastic bone resorption…and Osteocalcin (bone Gla protein) requires Vitamin K to indirectly support its function in bone remodeling” (2000). Additionally, Shier, Butler and Lewis found that “vitamin A is necessary for osteoblast and osteoclast activity during normal development… [and] vitamin C is required for collagen synthesis” (2002).
  6. 6. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 6 Prolonged stress also affects successful bone remodeling. It is known that “under stress, the body produces cortisol to help meet the challenges of fight or flight…if your body is under high levels of stress consistently, the cortisol builds up in your system, causing damage” (Markham, 2009). According to Marcy Holmes, a Nurse Practioner, Sustained high cortisol levels destroy healthy muscle and bone, slow down healing and normal cell regeneration, co-opt biochemical’s need to make other vital hormones, impair digestion, metabolism and mental function, and interfere with healthy endocrine function as well as weaken your immune system. When the adrenal glands are chronically overworked and straining to maintain high cortisol levels, they lose the capacity to produce DHEA in sufficient amounts. DHEA (the full name is dehydroepiandrosterone) is a precursor hormone to estrogen, progesterone, and testosterone, and is necessary to moderate the balance of hormones in your body. Insufficient DHEA contributes to fatigue, bone loss, loss of muscle mass, depression, aching joints, decreased sex drive, and impaired immune function (2004). Additionally, it is known that “when cortisol is used to treat arthritis, glucocorticoid excess can lead to bone loss, especially of trabecular bone, and result in osteoporosis” (Stipanuk, 2000). Due to the similar effects of high cortisol levels and the symptoms experienced in astronauts, paired with the increased stress levels experienced from space flight, it is hypothesized that increased cortisol production as a result of stress may also be a contributing factor for the increase in bone loss in astronauts. Because of the delicate balance of homeostasis, there is not a simple solution to resolve bone density loss. Many of the body’s organs experience different effects from the same chemical. For example, Parathyriod hormone (PTH) has the ability to “increase the resorption of bone salts and,
  7. 7. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 7 therefore, to release large amounts of calcium into the extracellular fluid…” but also “with increased levels of PTH, there is increased calcium reabsorption in the thick ascending loops of the Henle and distal tubes [of the kidneys]” (Shier, Butler & Lewis, 2002). PTH, like many other chemicals produced by the body, has to be maintained in precise amounts, and these amounts depend on the body’s current condition. Any lacking chemical creates a chain reaction as the body tries to compensate for this lack and still maintain homeostasis. Not knowing the precise chemical composition of the body at any given time prevents us from being able to appropriately supplement these chemicals. Additionally, even if we knew the precise cocktail of nutritional supplements to feed our astronauts, the processes by which these chemicals are used by the body may be altered in microgravity. Due to the increased rate of bone resorption, there is an excess of calcium in the extracellular fluid, causing the blood calcium ion level to become elevated. According to Shier, Butler and Lewis, increased levels of blood calcium ions depress the nervous system, making muscle contractions weak and reflexes sluggish (2002). A depressed nervous system cannot respond appropriately, and this includes the endocrine system, which is responsible for the hormone production required for bone metabolism and calcium homeostasis. Weak muscle contractions, due to increased blood calcium ion concentration, may be the reason exercise programs in microgravity have been ineffective. Estimating Bone Density Loss on a Mission to Mars Astronauts typically lose bone density at the rate of 1-2% per month for the duration of their time in microgravity (Moore & MacDougall, 2010). This cumulative bone loss increases the potential for fractures. With limited medical care in space, and the physical challenges of extra-vehicular activity and exploration, we must examine the potential bone loss effects on our astronauts prior to sending them on a Mars mission.
  8. 8. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 8 Several simulations on muscle mass and bone density loss were conducted to determine the extent of bone density loss on a trip to Mars. One such mission scenario, conducted by Carpenter, et al. (2010) estimated the first leg of travel to be 6 months, with a stay on Mars equal to 1 Earth year, and a 6 month return trip. Estimates of bone density and muscle mass based on this simulated trip indicate, “when the crew members arrive back on Earth, their hip bones will have lost approximately 33% of their fracture strength, and they will have lost approximately 48% of their muscle strength at the knee and 32% of their muscle strength at the ankle” (Carpenter, et al., 2010). With the technology currently available, other estimates of a manned mission to Mars include a 972 day scenario (Clement, 2005). This scenario assumes the use of a low energy Hohmann transfer, which is the most fuel-efficient way to transfer between planetary orbits. According to this mission scenario, using the current methods and systems available, the first leg of the trip will take 258 days, with a 455 day stay on the Martian surface, and a 258 day return trip (Clement, 2005). “The ultimate time of transit to Mars and back is uncertain because of the undetermined nature of the propulsion system to be employed” (Clement & Buckley, 2007). While estimates of bone density loss in microgravity vary, all fall within the range of 1-2% per month, with no signs of stabilizing at a reduced rate. According to Clement & Buckley, “unless the process reaches a plateau, which has not been observed during missions of up to 14 months duration, a 40% decrease in bone mass might occur for a spaceflight lasting two years” (2007). Using the 972 day trip estimate; the first leg of the trip in microgravity would be 258 days, the time exposed to the reduced gravity of the Martian surface would be 455 days at .38g, and the return trip in microgravity would be 258 days. Estimated bone loss upon reaching the Martian surface, using the 1% per month bone loss rate of microgravity, is approximately 8.6%. Using the 2% per month rate,
  9. 9. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 9 bone loss is an estimated 17.2%, giving an upper and lower range of 8.6%-17.2% bone loss for the first leg of the trip. It is hypothesized that the reduced gravity of .38g on the Martian surface would reduce the rate of bone loss proportionately, providing approximately 38% of the gravity of the Earth’s 1g environment. That equates to a 38% decrease in bone loss as compared to microgravity, giving an estimated upper and lower range of 9.4-18.8% for the 455 day rendezvous on the Martian surface. The return leg of the trip, at 258 days in microgravity, is an estimated 8.6%-17.2% bone loss. Therefore, the total bone loss estimated for the duration of a 972 day trip to Mars is 26.6-53.2%. Astronauts re-entering a 1g environment with this level of bone loss would require a severe amount of rehabilitation, and may experience permanent damage to their skeletal architecture if the body’s calcium balance is restored before the bone is fully rehabilitated (Hall, 1994). Whether the trip takes 2 years or 972 days, without more reliable mitigation techniques for the physiological effects of microgravity, we “would hardly be able to successfully execute an exploration mission” (Clement & Buckley, 2007). These estimates are modest in that they do not take into account any potential bone loss due to cosmic radiation exposure. The Impact of Bone Loss on Mars Operations As astronauts embark on interplanetary travel, they have many challenges ahead. Space exploration is both physically and mentally demanding. Not only do they have to overcome the extended effects of microgravity, and survive the physical stress of entering the Martian atmosphere, but they also have to be able to successfully conduct the exploration mission, and deal with any contingencies that arise on their own, as “radio communications with mission controllers will be difficult because of the transmission time delay between Mars and Earth” (Clement & Buckley, 2007).
  10. 10. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 10 Extra-vehicular activity is known to be physically demanding, and while on the Martian surface astronauts will be tasked with carrying the tools necessary to collect samples, take pictures, and conduct various research activities. “Much of their time will be spent searching for water and past and present evidence of Martian life forms, as well as conducting a wide range of scientific activities that cannot be accomplished by robotic exploration” (Clement & Buckley, 2007). With limited medical care available, keeping astronauts in top shape is a top priority. With the estimated bone density loss during travel to the Martian surface, astronauts are at an increased risk for fractures. A fracture has the potential to inhibit the success of the exploration mission by reducing the performance ability of one or more of the team members. Re-entry into a 1g environment also poses a high risk of fractures, and without more effective countermeasures, will leave the astronauts incapacitated. Nutrition and Exercise as Countermeasures The primary countermeasures used to reduce the level of bone density lost in microgravity are nutrition and exercise. While these countermeasures have proven to reduce bone density loss here on Earth, they have had limited success in space. The typical astronaut diet is selected from a list of foods available for space consumption, and is based on individual food preference. Nutritionists create balanced meals out of these selections, with the menu repeating approximately every 10 days. Additionally, supplements are provided for nutrients that may be lacking, such as vitamin D, which is rarely found in natural food (Clement, 2005). Nutrition as a countermeasure has proven ineffective, possibly because of the reduced inclination to eat and drink while in space. Additionally, the nutrients which enter the body are not used appropriately because the biochemical processes by which these chemicals are used may be altered by the lack of gravity.
  11. 11. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 11 Exercise is currently used as a countermeasure to reduce the effects of muscle atrophy, bone density loss, and cardiovascular deconditioning. Exercise is conducted on a cycle ergometer, the iRed resistance exercise device, and a modified treadmill (Clement, 2005). According to a study conducted by Trappe et al., “the available data from humans that have flown in space for 6 mo or longer show that muscle mass and performance are not protected despite exercise countermeasures” (2008). Future Considerations Other potential countermeasures are currently being studied and tested for use in microgravity. One piece of equipment used to conduct cardiovascular and other physiological research onboard the ISS is the Lower Body Negative Pressure (LBNP) device. It provides the lower body with a negative pressure environment, which causes the cardiovascular system to respond by increasing blood pressure to maintain flow to the upper body and head, similar to a 1-g environment (Clement, 2005). This negative pressure on the lower body may provide valuable insight into the effects of an intermittent gravitational environment on the cardiovascular system. Also under consideration is the administration of pharmaceuticals in space. Current investigations of biophosphonates are being conducted in microgravity “to determine if alendronate, an antiresorptive agent to treat osteoporosis, is an effective countermeasure to spaceflight induced bone loss” (National Aeronautics and Space Administration, 2011). It is hypothesized that because vitamins are not utilized by the body in the same manner as they are on Earth, pharmaceuticals would also have limited absorption and therefore limited effectiveness. One novel idea is to provide pneumatic pressure to the feet to simulate the feeling of standing on a floor (Astrobiology: The Living Universe, 2000). Continued studies on pneumatic space boots have shown to slow the rate of muscle atrophy, and may also have an effect on bone loss. While this idea has shown promise in preliminary tests, its effects in a microgravity environment have yet to be proven.
  12. 12. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 12 Studies have shown that exercise performed on a vibrating platform increased muscle forces substantially over exercise performed alone (Massachusetts Institute of Technology, n.d.). Additionally, in a study using sheep, results indicate “barely perceptible vibrations may generate enough strain to stimulate bone growth”, providing another potential option for use onboard the space station. The Massachusetts Institute of Technology (MIT) is currently designing a space suit for use inside the space shuttle to bring mechanical loading back to the body. The Gravity Loading Countermeasure Skinsuit (GLCS) is “made of elastic mesh…[is] cut short and has stirrups that loop over the feet, creating a stretch that stresses the legs and pulls slightly at the shoulders” (Klotz, 2010). According to Waldie and Newman, “the elastic mesh of the GLCS can create a loading regime that gradually increases in hundreds of stages from the shoulders to the feet, thereby reproducing the weight-bearing regime normally imparted by gravity with much higher resolution” (2010). Russian cosmonauts have used a device called the penguin suit, which retains a similar concept to the GLCS, to provide mechanical loading to the weight-bearing bones of the body (Clement, 2005). Although the penguin suit has been regularly used for decades, not much is known about the effectiveness of its design, as its use has been poorly documented. All of the physiological effects experienced by astronauts are due to a lack of gravity, and “although improvements in exercise protocols, changes in diet, or pharmaceutical one at-a-time treatments of single systems may be of value, they are unlikely to adequately eliminate the full range of physiological deconditioning induced by weightlessness (Clement & Buckley, 2007). Artificial Gravity Homeostasis of the body depends on the Earth-normal condition of gravity, as the processes of the body are adapted to its effects. Although much has been learned from addressing individual physiological processes and systems, the best comprehensive solution is to bring back what was missing…gravity.
  13. 13. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 13 Rather than addressing each individual system in a piecemeal fashion, which is only valid if the principle of superposition holds for the combined effect of these interacting subsystems, artificial gravity stimulates all of the physiological systems simultaneously by reproducing the normal Earth gravitational environment (Clement & Buckley, 2007). Currently scientists and engineers are working on ways to bring gravity to space. Designs of a short-radius centrifuge to create artificial gravity onboard spacecraft are being tested at MIT. The proposed 2-arm centrifuge would have a 2m radius, be able to accommodate two astronauts at the same time, and could be run by human power (pedaling bicycle- style) (Hsu, 2010).This would enable the cardiovascular strengthening from gravity and the cardio workout to be conducted simultaneously. Ground-based studies indicate artificial gravity “has performed as effectively as the current types of countermeasures aboard the ISS for the cardiovascular system” (Massachusetts Institute of Technology, n.d.) However; few studies have focused on the musculoskeletal effects of this system. Recommendations Based on the positive results in ground-based studies using low-level vibration on sheep, a vibration study should be conducted onboard the ISS to determine if these results also apply to humans in microgravity. Vibration shows promising results to increase bone density, and could easily be added to the astronauts exercise program or combined with exercises to improve the quality and efficiency of time spent exercising. Based on the specific physiological changes experienced in microgravity, and the low-level vibration studies, it is hypothesized that massage of the lower body, which has great benefits on Earth, may also provide benefits to astronauts in microgravity. In addition to increasing the blood flow, which is necessary for bone metabolism, massage has been shown to drastically reduce cortisol levels in humans.
  14. 14. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 14 Reducing cortisol has multiple effects, such as positively influencing bone metabolism; reducing muscle fatigue; improving immune function; improving healing and normal cell regeneration; improving digestion, metabolism and mental function; and improving the production of DHEA, “a precursor hormone necessary to moderate the balance of hormones in your body” (Holmes, 2004). One additional exercise recommended for inclusion in the ISS exercise regimen is the seated calf-raise. Although standing calf-raises are currently used to prevent bone density loss and muscle fatigue, considerable muscle mass is lost in the soleus muscle. Executing the calf-raise from the seated position isolates the soleus muscle, and is safe and easy to perform (Balachandran, 2010; Glenn, n.d.). Artificial gravity is clearly the comprehensive solution to the effects of microgravity, and ground- based research should be continued on the short-radius centrifuge, as well as engineering a centrifuge for use during interplanetary travel. Conclusion The general consensus is that without more effective mitigation techniques, the physiological effects of microgravity will prevent interplanetary travel. In light of the complexity of addressing individual physiological systems, artificial gravity has become a top research priority for a Mars mission. As planet Earth becomes more crowded, and with the depletion of natural resources, further industrialization and colonization efforts will be explored on other potentially habitable planets, such as Mars. These missions will push our intellectual and physical ability as we strive to achieve both creative and ingenious solutions in our conquest of space. For mankind, the challenges we face are hardly unexpected. Whether on Earth, or looking at the Earth from space, our eyes have always been on what’s over the horizon.
  15. 15. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 15 References Astrobiology: The Living Universe. (2000). Countermeasures Against Zero-G. Retrieved from http://library.thinkquest.org/C003763/index.php?page=adapt04 Balachandran, A. (2010). How to build and strengthen your calf muscle? Exercise Biology: The Science of Exercise. Retrieved from http://www.exercisebiology.com/index.php/site/articles/how_to_build_and_stretch_your_calf_ muscle/ Beattie-Moss, M. (2011). How does microgravity affect astronauts? Pennsylvania State University. Retrieved from http://www.physorg.com/news/2011-08-microgravity-affect-astronauts.html Clement, G. (2005). Fundamentals of Space Medicine. Space Technology Library. Mircocosm: CA. Springer: NY. Clement, G., Bukley, A. (2007). Artificial Gravity. Space Technology Library. Microcosm: CA. Springer: NY. Glenn, L. (n.d.). Seated Calf Raise Machine. Exercises. Retrieved from http://www.musclemagfitness.com/bodybuilding/exercises/seated-calf-raise-machine.html Hadjidakis, D., Androulakis, L. (2006). Bone remodeling. [Abstract]. National Center for Biotechnology Information. Annals of the New York Academy of Sciences, 1092:385-396. Hall, T. (1994). The Architecture of Artificial-Gravity Environments for Long-Duration Space Habitation. The University of Michigan. Retrieved from http://www.artificial- gravity.com/Dissertation/2_1.htm Holmes, M. (2004). Adrenal Fatigue-the effects of stress and high cortisol levels. Retrieved from http://www.womentowomen.com/adrenalfatigue/effectsofhighcortisol.aspx
  16. 16. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 16 Hsu, J. (2010). New Artificial Gravity Tests in Space Could Help Astronauts. Retrieved from http://www.space.com/8384-artificial-gravity-tests-space-astronauts.html Markham, A. (2009). Can a Massage Program Effectively Reduce Fatigue in Aviation Personnel? Embry- Riddle Aeronautical University. Markham, A. (2012). Methods of Retaining Muscle and Bone Density on Long Duration Spaceflights. Embry-Riddle Aeronautical University. Massachusetts Institute of Technology. (n.d.) Modeling the benefits of an artificial gravity countermeasure coupled with exercise and vibration. Retrieved from http://web.mit.edu/aeroastro/www/people/dnewman/pdf2/DJN_GoelKaderkaNewman- 3.46.pdf Moore, S., MacDougall, H. (2010). Journey to Mars: Physiological Effects and Operational Consequences of Long-Duration Microgravity Exposure. Journal of Cosmology, 2010, Vol 12, 3781-3793 Naslund, J., Naslund, S., Lundeberg, E., Lindberg, L., Lund, I. (2011). Bone blood flow is influenced by muscle contractions. Journal of Biomedical Science and Engineering, 4, 490-496. doi: 10.4236/jbise.2011.47062 National Aeronautics and Space Administration. (2011). International Space Station. Biophosphonates as a Countermeasure to Space-Flight Induced Bone Loss. Retrieved from http://www.nasa.gov/mission_pages/station/research/experiments/Bisphosphonates.html National Space Biomedical Research Institute. (n.d.). How the human body changes in space. Retrieved from http://www.nsbri.org/humanphysspace/introduction/intro-bodychanges.html
  17. 17. ESTIMATION AND MITIGATION OF BONE DENSITY LOSS 17 Shier D., Butler, J., Lewis, R. (2002). Hole’s Human Anatomy & Physiology. Ninth Edition. McGraw-Hill, NY. Stipanuk, M. (2000). Biochemical and Physiological Aspects of Human Nutrition. WB. Saunders Company. Tobin, B., Uchakin, P., Leeper-Woodford, S. (2002). Insulin secretion and sensitivity in space flight: diabetogenic effects. [Abstract]. National Center for Biotechnology Information. Nutrition. 10:842-848. Trappe, S., Costill, D., Gallagher, P., Creer, A., Peters, J., Evans, H. …Fitts, R. (2008). Exercise in space: human skeletal muscle after 6 months aboard the International Space Station. Journal of Applied Physiology, 106, 1159-1168. doi: 10.1152/japplphysiol.91578.2008

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