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The Effect of Spaceflight on Bone Cell Cultures

Understanding the response of bone to mechanical loading (unloading) is extremely important in defining the means of adaptation of the body to a variety of environmental conditions such as during heightened physical activity or in extended explorations of space or the sea floor. The mechanisms of the adaptive response of bone are not well defined, but undoubtedly they involve changes occurring at the cellular level of bone structure. This proposal has intended to examine the hypothesis that the loading (unloading) response of bone is mediated by specific cells through modifications of their activity cytoskeletal elements, and/or elaboration of their extracellular matrices. For this purpose, this laboratory has utilized the results of a number of previous studies defining molecular biological, biochemical, morphological, and ultrastructural events of the reproducible mineralization of a primary bone cell (osteoblast) culture system under normal loading (1G gravity level). These data and the culture system then were examined following the use of the cultures in two NASA shuttle flights, STS-59 and STS-63. The cells collected from each of the flights were compared to respective synchronous ground (1G) control cells examined as the flight samples were simultaneously analyzed and to other control cells maintained at 1G until the time of shuttle launch, at which point they were terminated and studied (defined as basal cells). Each of the cell cultures was assayed in terms of metabolic markers- gene expression; synthesis and secretion of collagen and non-collagenous proteins, including certain cytoskeletal components; assembly of collagen into macrostructural arrays- formation of mineral; and interaction of collagen and mineral crystals during calcification of the cultures. The work has utilized a combination of biochemical techniques (radiolabeling, electrophoresis, fluorography, Western and Northern Blotting, and light microscopic immunofluorescence) and structural methods (conventional and high voltage electron microscopy, inununocytochemistry, stereomicroscopy, and 3D image reconstruction). The studies have provided new knowledge of aspects of bone cell development and structural regulation, extracellular matrix assembly, and mineralization during spaceflight and under normal gravity. The information has contributed to insights into the means in general by which cells respond and adapt to different conditions of gravity (loading). The data may as well have suggested an underlying basis for the observed loss of bone by vertebrates, including man, in microgravity; and these scientific results may have implications for understanding bone loss following fracture healing and extended periods of inactivity such as during long-term bedrest.

Landis, William J.↗

The Hopper: A Wearable Robotic Device Testbed for Micro-Gravity Bone-Loading Proof-of-Concept

Wearable robotic systems are showing increased potential for addressing crew countermeasures needs. Wearable robots offer a compactness, programmability, and eccentric loading capability not present in more conventional exercise equipment. Correspondingly, advancements in the man to machine interface has progressed, allowing for higher loads to be applied directly to the person in new and novel ways. Recently, the X1 exoskeleton, a lower extremity wearable robot originally designed for mobility assistance and rehabilitation, underwent human subject testing to assess its potential as a knee dynamometer. This was of interest to NASA physiologists because currently strength is not assessed in flight due to hardware limitations, and thus there is a poor understanding of the time course of in-flight changes to muscle strength. The study concluded that the X1 compared well with the Biodex, the "gold standard" in terrestrial dynamometry, with coefficients of variation less than 6.0%. In a following study, the X1 powered ankle was evaluated for its efficacy in exercising calf muscles. Current on-orbit countermeasures equipment does not adequately protect the calf from atrophy. The results of this study were also positive (targeted muscle activity demonstrated via comparing pre- and post-exercise magnetic resonance imaging T2 measurements), again showing the efficacy of wearable robotic devices for addressing the countermeasure needs of our astronauts. Based on these successes and lessons learned, the Grasshopper was co-developed between IHMC (Florida Institute for Human and Machine Cognition) and NASA. The Grasshopper, or the Hopper for short, is a wearable robotic device designed to address muscle and bone density loss for astronauts spending extended periods of time in micro-gravity. The Grasshopper connects to the user's torso like a hiking backpack, over the shoulders and around the waist. At the feet are footplates that strap to the user. There are two actuators, one at each "knee" joint, which are capable of high fidelity torque control. Because the Hopper uses motors instead of gravity to create the load on the user, the device is suited for use on space missions. Exercise in zero-gravity conditions is critical to maintain muscle strength and bone mass. In operation, the actuators try to fold up, or collapse, the device, putting a compressive load between the user's feet and torso. This force is similar to carrying a heavy backpack. The user then bends and extends his or her knees, replicating a weightlifting squat exercise. The applied load is precisely controlled by a computer, and can be programmed to simulate gravitation loads or any desired load prescription, such as free-weight squat exercise. It is even possible to perform eccentric exercises, or negatives, without the need for a spotter. Because the hip joints, as well as the spine and long leg bones, are in the applied load path, there is the potential to stimulate bone growth, countering the typical bone loss when astronauts return from extended duration space travel.

Beck, C. E.↗

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Young, D. R.↗

Skeletal response

The effect of weightlessness on bone mineral content during prolonged space flight was investigated. The mineral content changes which occurred during Apollo 14, 15, and 16 as measured by photon absorptiometry techniques are presented and compared. Bed rest served as an experimental model to assess the bone mineral changes, and to determine what remedial measures might be used to stem the tide of bone mineral loss. It is concluded that loss of mineral from bone due to the state of weightlessness is comparable to that observed in bed rest subjects.

Paul C. Rambaut↗

Techniques for determination of impact forces during walking and running in a zero-G environment

One of the deleterious adaptations to the microgravity conditions of space flight is the loss of bone mineral content. This loss appears to be at least partially attributable to the minimal skeletal axial loading concomitant with microgravity. The purpose of this study was to develop and fabricate the instruments and hardware necessary to quantify the vertical impact forces (Fz) imparted to users of the space shuttle passive treadmill during human locomotion in a three-dimensional zero-gravity environment. The shuttle treadmill was instrumented using a Kistler forceplate to measure vertical impact forces. To verify that the instruments and hardware were functional, they were tested both in the one-G environment and aboard the KC-135 reduced gravity aircraft. The magnitude of the impact loads generated in one-G on the shuttle treadmill for walking at 0.9 m/sec and running at 1.6 and 2.2 m/sec were 1.1, 1.7, and 1.7 G, respectively, compared with loads of 0.95, 1.2, and 1.5 G in the zero-G environment.

Greenisen, Michael↗

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Lewandowski, B. E.↗

Stationary Apparatus Would Apply Forces of Walking to Feet

A proposed apparatus would apply controlled cyclic forces to both feet for the purpose of preventing the loss of bone density in a human subject whose bones are not subjected daily to the mechanical loads of normal activity in normal Earth gravitation. The apparatus was conceived for use by astronauts on long missions in outer space; it could also be used by bedridden patients on Earth, including patients too weak to generate the necessary forces by their own efforts. The apparatus (see figure) would be a modified version of a bicycle-like exercise machine, called the cycle ergometer with vibration isolation system (CEVIS), now aboard the International Space Station. Attached to each CEVIS pedal would be a computer-controlled stress/ vibration exciter connected to the heel portion of a special-purpose pedal. The user would wear custom shoes that would amount to standard bicycle shoes equipped with cleats for secure attachment of the balls of the feet to the special- purpose pedals. If possible, prior to use of the apparatus, the human subject would wear a portable network of recording accelerometers, while walking, jogging, and running. The information thus gathered would be fed to the computer, wherein it would be used to make the exciters apply forces and vibrations closely approximating the forces and vibrations experienced by that individual during normal exercise. It is anticipated that like the forces applied to bones during natural exercise, these artificial forces would stimulate the production of osteoblasts (bone-forming cells), as needed to prevent or retard loss of bone mass. In addition to helping to prevent deterioration of bones, the apparatus could be used in treating a person already suffering from osteoporosis. For this purpose, the magnitude of the applied forces could be reduced, if necessary, to a level at which weak hip and leg bones would still be stimulated to produce osteoblasts without exposing them to the full stresses of walking and thereby risking fracture.

Hauss, Jessica↗

Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there is still high variability in individual response. Three additional crewmembers have been recruited to participate in this experiment, with expected completion in late 2011.

LeBlanc, Adrian↗

Tibial changes in experimental disuse osteoporosis in the monkey

The mechanical properties and structural changes in the monkey tibia with disuse osteoporosis and during subsequent recovery are investigated. Bone mending stiffness is evaluated in relation to microscopic changes in cortical bone and Norland bone mineral analysis. Restraint in the semireclined position is found to produce regional losses of bone most obviously in the anterior-proximal tibiae. After six months of restraint, the greatest losses of bone mineral in the proximal tibiae range from 23 percent to 31 percent; the largest changes in bone stiffness range from 36 percent to 40 percent. Approximately eight and one-half months of recovery are required to restore the normal bending properties. Even after 15 months of recovery, however, the bone mineral content does not necessarily return to normal levels. Histologically, resorption cavities in cortical bone are seen within one month of restraint; by two and one-half months of restraint there are large resorption cavities subperiosteally, endosteally, and intracortically. After 15 months of recovery, the cortex consists mainly of first-generation haversian systems. After 40 months, the cortex appears normal, with numerous secondary and tertiary generations of haversian systems.

Young, D. R.↗

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. We aimed to elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis, we performed global postnatal deletion of Atg12 using tamoxifen-inducible Cre. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. qPCR revealed increased expression of pro-osteoclastogenic cytokines in bone and marrow respectively in male iKOs compared to controls. Microcomputed tomography revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. Histology showed that compared to male controls, male iKOs had a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of pro-osteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

Atg12↗

Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System

Exposure to space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized exposure to ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-week old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 mega electron volts per nucleon) or high-LET (sup 56) Fe ions (600 mega electron volts per nucleon) using either low (5 or 10 centigrays) or high (50 or 200 centigrays) doses at NASAs Space Radiation Lab at Brookhaven National Lab (NSRL/BNL). Tissues were harvested 5 weeks or 1 year after irradiation and bones were analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions. Cell lysates were analyzed for select groups by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) during the proliferative phase or the mineralizing phase, and differentiation was analyzed by imaging mineralized nodules (percentage surface area). Representative genes were selected for expression analyses, including cell proliferation (PCNA, Cdk2, p21, p53), differentiation (Runx2, Alpl, Bglap), oxidative metabolism (Catalase, GPX, MnSOD, CuZnSOD, iNos, Foxo1), DNA-damage repair (Gadd45), or apoptosis (Caspase 3). As expected, a high dose (200 centigrays), but not low doses, of either (sup 56) Fe or protons caused a loss of cancellous bone volume per total volume. Marrow cells produced mineralized nodules ex vivo regardless of radiation type or dose; (sup 56) Fe (200 centigrays) inhibited median nodule area by more than 90 percent at 5 weeks and 1 year post-irradiation, compared to controls. At 5 weeks post exposure, irradiation with protons or (sup 56) Fe caused few changes in gene expression levels during osteoblastogenesis, although a high dose of (sup 56) Fe (200 centigrays) increased levels of Catalase and Gadd45. In addition, supplementing cell culture media with SOD protected marrow-derived osteoprogenitors from the damaging effects of exposure to low-LET ((sup 137) Cs gamma) if irradiated in vitro, but had limited protective effects on high-LET (sup 56) Fe-exposed cells. In sum, exposure of mice to either protons or (sup 56) Fe at a relatively high dose (200 cGy) caused persistent bone loss, whereas only high-LET (sup 56) Fe increased expression of redox-related genes and inhibited osteoblastogenesis, albeit to a limited extent. We conclude that high-LET irradiation impaired osteoblastogenesis and regulated steady-state gene expression of select redox-related genes during osteoblastogenesis, which may contribute to persistent bone loss.

ionizing radiation↗

Alterations of collagen matrix in weight-bearing bones during skeletal unloading

Skeletal unloading induces loss of bone mineral density in weight-bearing bones. The objectives of this study were to characterize the post-translational modifications of collagen of weight-bearing bones subjected to hindlimb unloading for 8 weeks. In unloaded bones, tibiae and femurs, while the overall amino acid composition was essentially identical in the unloaded and control tibiae and femurs, the collagen cross-link profile showed significant differences. Two major reducible cross-links (analyzed as dihydroxylysinonorleucine and hydroxylysinonorleucine) were increased in the unloaded bones. In addition, the ratios of the former to the latter as well as pyridinoline to deoxypyridinoline were significantly decreased in the unloaded bones indicating a difference in the extent of lysine hydroxylation at the cross-linking sites between these two groups. These results indicate that upon skeletal unloading the relative pool of newly synthesized collagen is increased and it is post-translationally altered. The alteration could be associated with impaired osteoblastic differentiation induced by skeletal unloading that results in a mineralization defect.

Non-NASA Center↗

The Art of Space Flight Exercise Hardware: Design and Implementation

The design of space flight exercise hardware depends on experience with crew health maintenance in a microgravity environment, history in development of flight-quality exercise hardware, and a foundation for certifying proper project management and design methodology. Developed over the past 40 years, the expertise in designing exercise countermeasures hardware at the Johnson Space Center stems from these three aspects of design. The medical community has steadily pursued an understanding of physiological changes in humans in a weightless environment and methods of counteracting negative effects on the cardiovascular and musculoskeletal system. The effects of weightlessness extend to the pulmonary and neurovestibular system as well with conditions ranging from motion sickness to loss of bone density. Results have shown losses in water weight and muscle mass in antigravity muscle groups. With the support of university-based research groups and partner space agencies, NASA has identified exercise to be the primary countermeasure for long-duration space flight. The history of exercise hardware began during the Apollo Era and leads directly to the present hardware on the International Space Station. Under the classifications of aerobic and resistive exercise, there is a clear line of development from the early devices to the countermeasures hardware used today. In support of all engineering projects, the engineering directorate has created a structured framework for project management. Engineers have identified standards and "best practices" to promote efficient and elegant design of space exercise hardware. The quality of space exercise hardware depends on how well hardware requirements are justified by exercise performance guidelines and crew health indicators. When considering the microgravity environment of the device, designers must consider performance of hardware separately from the combined human-in-hardware system. Astronauts are the caretakers of the hardware while it is deployed and conduct all sanitization, calibration, and maintenance for the devices. Thus, hardware designs must account for these issues with a goal of minimizing crew time on orbit required to complete these tasks. In the future, humans will venture to Mars and exercise countermeasures will play a critical role in allowing us to continue in our spirit of exploration. NASA will benefit from further experimentation on Earth, through the International Space Station, and with advanced biomechanical models to quantify how each device counteracts specific symptoms of weightlessness. With the continued support of international space agencies and the academic research community, we will usher the next frontier in human space exploration.

Beyene, Nahom M.↗

Preliminary Assessment of Artificial Gravity Impacts to Deep-Space Vehicle Design

Even after more than thirty years of scientific investigation, serious concerns regarding human physiological effects of long-duration microgravity exposure remain. These include loss of bone mineral density, skeletal muscle atrophy, and orthostatic hypertension, among others. In particular, "Safe Passage: Astronaut Care for Exploration Missions," states "loss of bone density, which apparently occurs at a rate of 1% per month in microgravity, is relatively manageable on the short-duration missions of the space shuttle, but it becomes problematic on the ISS [International Space Station]. ...If this loss is not mitigated, interplanetary missions will be impossible." While extensive investigations into potential countermeasures are planned on the ISS, the delay in attaining full crew complement and onboard facilities, and the potential for extending crews tours of duty threaten the timely (< 20 years!) accumulation of sufficient data for countermeasures formulation. Indeed, there is no guarantee that even with the data, a practical or sufficiently robust set of countermeasures will be forthcoming. Providing an artificial gravity (AG) environment by crew centrifugation aboard deep-space human exploration vehicles, long a staple technique of science fiction, has received surprisingly limited engineering assessment. This is most likely due to a number of factors: the lack of definitive design requirements, especially acceptable artificial gravity levels and rotation rates, the perception of high vehicle mass and performance penalties, the incompatibility of resulting vehicle configurations with space propulsion options (i.e., aerocapture), the perception of complications associated with de-spun components such as antennae and photovoltaic arrays, and the expectation of effective crew micro-gravity countermeasures. These perception and concerns may have been overstated, or may be acceptable alternatives to countermeasures of limited efficacy. This study was undertaken as an initial step to try to understand the implications of and potential solutions to incorporating artificial gravity in the design of human deep-space exploration vehicles. Of prime interest will be the mass penalties incurred by incorporating AG, along with any mission performance degradation.

Joosten, B. Kent↗

Bone mineral measurement - Skylab experiment M-078

Experimental observations of loss of bone mineral due to prolonged bedrest or weightlessness are reported. A new, precise method was employed that featured an essentially monoergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral in the radius, ulna, and os calcis by the absorptiometric technique. Variable but small losses were found during 4-6 weeks of bedrest; losses of up to 40% were noted in the os calcis after 9 months. When the technique was used during the Apollo 14, 15, and 16 missions, only one crewmen showed significant losses in the os calcis and none in the radius or ulna. The variability recorded during bedrest was connected with the initial 24-hr urinary hydroxyproline excretion and the initial os calcis mineral content. The relevance of prediction terms based on bedrest data to Skylab and longer missions is discussed.

Vogel, J. M.↗

Foot Forces during Treadmill Exercise on the International Space Station

Exercise has been the primary countermeasure to combat musculoskeletal changes during the approximately 6 month missions to the International Space Station (ISS). However, these countermeasures have not been successful in preventing loss of bone mineral density in the spine and hip of astronauts. We examined lower extremity loading during typical bouts of on-orbit exercise performed by 4 ISS crew members on the ISS treadmill (TVIS) and during locomotor activities on earth (1g). In-shoe forces were monitored at 128Hz using force-measuring insoles placed inside the shoes of the exercising crewmember, stored temporarily on Flash cards, and down-linked via satellite for analysis. Custom software extracted peak forces from up to 30 minutes of locomotor activity. All on-orbit loading conditions for walking and running resulted in peak forces and impact loading rates that were significantly less than those measured in 1g. Typical single leg loads on-orbit in walking and running were 0.860 plus or minus 0.04 body weights (BW) and 1.339 plus or minus 0.07 BW compared to 1.2 plus or minus 0.036 BW and 2.36 plus or minus 0.07 BW in 1g BW respectively. These results indicate that typical exercise on the ISS treadmill does not generate 1g-like loading conditions. This may be partly responsible for the loss of bone mineral density that has been observed in these and other crew members. Since on-orbit treadmill exercise requires a restraining load to return the crew member to the treadmill surface, more studies are required to enable comfortable full body weight loading to be applied.

Cavanagh, Peter R.↗

Comparison of Upright Gait with Supine Bungee-Cord Gait

Running on a treadmill with bungee-cord resistance is currently used on the Russian space station MIR as a countermeasure for the loss of bone and muscular strength which occurs during spaceflight. However, it is unknown whether ground reaction force (GRF) at the feet using bungee-cord resistance is similar to that which occurs during upright walking and running on Earth. We hypothesized-that the DRAMs generated during upright walking and running are greater than the DRAMs generated during supine bungee-cord gait. Eleven healthy subjects walked (4.8 +/- 0.13 km/h, mean +/- SE) and ran (9.1 +/- 0.51 km/h) during upright and supine bungee-cord exercise on an active treadmill. Subjects exercised for 3 min in each condition using a resistance of 1 body weight calibrated during an initial, stationary standing position. Data were sampled at a frequency of 500Hz and the mean of 3 trials was analyzed for each condition. A repeated measures analysis of variance tested significance between the conditions. Peak DRAMs during upright walking were significantly greater (1084.9 +/- 111.4 N) than during supine bungee-cord walking (770.3 +/- 59.8 N; p less than 0.05). Peak GRFs were also significantly greater for upright running (1548.3 +/- 135.4 N) than for supine bungee-cord running (1099.5 +/- 158.46 N). Analysis of GRF curves indicated that forces decreased throughout the stance phase for bungee-cord gait but not during upright gait. These results indicate that bungee-cord exercise may not create sufficient loads at the feet to counteract the loss of bone and muscular strength that occurs during long-duration exposure to microgravity.

Boda, Wanda L.↗

Immobilization-associated osteoporosis in primates

Osteopenic changes in the tibial compact bone of fifteen adult male monkeys immobilized for up to 7 months are examined histologically. Osteonal formation in the proximal tibia is analyzed. The analysis reveals the loss of haversian bone in the proximal tibia, increased activation with excessive depth of penetration of osteoclastic activity, rapid bone loss, and resorption cavities of irregular size and orientation. Osteonal formation following reambulation is examined; the recovery of cortical is a repair and rejuvenation process characterized by refilling of resorption cavities and remodeling activities.

Young, D. R.↗