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At least 217 records · Page 12

Skeletal Recovery Following Long-Duration Spaceflight Missions as Determined by Preflight and Postflight DXA Scans of 45 Crew Members

Introduction: The loss of bone mineral in astronauts during spaceflight has been investigated throughout the more than 40 years of bone research in space. Consequently, it is a medical requirement at NASA that changes in bone mass be monitored in crew members by measurements of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). This report is the first to evaluate medical data to address the recovery of bone mineral that is lost during spaceflight. Methods: DXA scans are performed before and after flight in astronauts who serve on long-duration missions (4-6 months) to ensure that medical standards for flight certification are met, to evaluate the effects of spaceflight and to monitor the restoration to preflight BMD status after return to Earth. Through cooperative agreements with the Russian Space Agency, the Bone and Mineral Lab at NASA Johnson Space Center (Houston, TX), also had access to BMD data from cosmonauts who had flown on long-duration missions yielding data from a total of 45 individual crew members. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing); plotted data were fitted to an exponential mathematical model that determined i) BMD change at day 0 after landing and ii) the number of days after which 50% of the lost bone was recovered ("Recovery Half-Life"). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. Results: In sum, averaged losses of bone mineral after spaceflight ranged between 2-9% for sites in the axial and appendicular skeleton. The fitted postflight BMD values predicted a 50% recovery of bone loss for all sites within 9 months.

Sibonga, J. D.↗

Intake of Fish and Omega-3 (n-3) Fatty Acids: Effect on Humans During Actual and Simulated Weightlessness

Space flight has many negative effects on human physiology, including bone and muscle loss. Bone and muscle are two systems that are positively affected by dietary intake of fish and n-3 fatty acids. The mechanism is likely to be related to inhibition by n-3 fatty acids of inflammatory cytokines (such as TNF) and thus inhibition of downstream NF-kB activation. We have documented this effect in a 3-dimensional cell culture model, where NF-kB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have also indentified that NF-kB activation in peripheral blood mononuclear cells of Space Shuttle crews. We found that after Shuttle flights of ~2 wk, expression of the protein p65 (evidence of NF-kB activation) was increased at landing (P less than 0.001). When evaluating the effects of n-3 fatty acid intake on bone breakdown after 60 d of bed rest (a weightlessness analog). We found that after 60 d of bed rest, greater intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). We also evaluated the relationship of fish intake and bone loss in astronauts after 4 to 6 mo missions on the International Space Station. Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = 0.46, P less than 0.05). Together, these findings provide evidence of the cellular mechanism by which n-3 fatty acids can inhibit bone loss, and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with space flight. This study was supported by the NASA Human Research Program.

Smith, S. M.↗

Oxidative Stress Responses to Simulated Spaceflight in Mineralized and Marrow Compartments of Bone and Associated Vasculature

Long-term spaceflight causes profound changes to the musculoskeletal system attributable to unloading and fluid shifts in microgravity. Future space explorations beyond the earth’s magnetosphere will expose astronauts to space radiation, which may cause additional skeletal deficits that are not yet fully understood. Our long-term goals are twofold: to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures if necessary. Our central hypothesis is that oxidative stress plays a key role in progressive bone loss and vascular dysfunction caused by spaceflight. In animal’s models, overproduction of free radicals is associated with increased bone resorption, lower bone formation, and decrements in bone mineral density and structure which can ultimately lead to skeletal fragility. Evidence in support of a possible causative role for oxidative stress in spaceflight-induced bone loss derive from knockout and transgenic mouse studies and the use of pharmacological interventions with known anti-oxidant properties. In our studies to simulate spaceflight, 16-wk old, male C56Bl/6J mice were assigned to one of four groups: hind limb unloading to simulate weightlessness (HU), normally loaded Controls (‘NL’) (sham irradiated, no hind limb unloading), irradiated at NASA Space Radiation Laboratory ‘IR’ with 1-2Gy of (600MeV/n) alone, or in combination with protons (0.5Gy Protons/0.5Gy 56Fe), (IR) or both hind limb unloaded and irradiated, ‘HU+IR’. Mice were exposed to radiation 3 days after initiating HU and tissues harvested were 1-14 days after initiating treatments for analyses. Results from our laboratories, which employ various biochemical, gene expression, functional, and transgenic animal model methods, implicate dynamic regulation of redox-related pathways by spaceflight-related environmental factors. As one example, we found that combined HU and radiation exposure caused oxidative damage in skeletal tissues (lipid peroxidation) of wildtype mice, whereas bone from transgenic mice that overexpress human catalase in mitochondria were protected. Interestingly, marrow cells grown under culture conditions that select for endothelial progenitor cells (EPC), showed that HU but not IR reduced EPC cell migration; in contrast HU and IR each inhibited growth of marrow-derived osteoblast progenitors. Taken together, these results indicate that unloading and ionizing elicit distinct effects on progenitor and mature cells of vascular and skeletal tissue, and that oxidative damage may contribute to skeletal and vascular deficits that may emerge during extended space travel.

Globus, R. K.↗

Ultrasonic bone densitometer

A device, for measuring the density of a bone structure so as to monitor the calcium content, is described. A pair of opposed spaced ultrasonic transducers are held within a clamping apparatus closely adjacent the bone being analyzed. These ultrasonic transducers incude piezoelectric crystals shaped to direct signals through the bone encompassed in the heel and finger of the subject being tested. A pulse generator is coupled to one of the transducers and generates an electric pulse for causing the transducers to generate an ultrasonic sound wave which is directed through the bone structure to the other transducer. An electric circuit, including an amplifier and a bandpass filter couples the signals from the receiver transducer back to the pulse generator for retriggering the pulse generator at a frequency proportional to the duration that the ultrasonic wave takes to travel through the bone structure being examined.

Hoop, J. M.↗

Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (≥50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level ≥8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations were identified in women. Bone turnover in older Hispanic men with DM2 in our study does not reflect normal pattern of skeletal aging. It is unclear why similar results were not identified in women. We will continue to follow this cohort to investigate longitudinal trend of changes of bone turnover and its relationship with HbA1c in both men and women of this cohort.

Rianon, N.↗

Intake of Fish and Omega-3 (N-3) Fatty Acid: Effect on Humans during Actual and Simulated Weightlessness

Space flight has many negative effects on human physiology, including bone and muscle loss. These are some of the systems on which intakes of fish and n-3 fatty acids have positive effects. These effects are likely to occur through inhibition of inflammatory cytokines (such as TNFalpha) and thus inhibition of downstream NF-KB activation. We documented this effect in a 3D cell culture model, where NF-KB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have extended these studies and report here (a) NF-KB expression in peripheral blood mononuclear cells of Space Shuttle crews on 2-wk missions, (b) the effects of n-3 fatty acid intake after 60 d of bed rest (a weightlessness analog), and (c) the effects of fish intake in astronauts after 4 to 6 mo on the International Space Station. After Shuttle flights of ~2 wk, NFKB p65 expression at landing was increased (P less than 0.001). After 60 d of bed rest, higher intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = -0.46, P less than 0.05). Together with our earlier findings, these data provide mechanistic cellular and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with spaceflight. This study was supported by the NASA Human Research Program.

Smith, Scott M.↗

Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

Globus, Ruth↗

Effect of Microgravity on Bone Tissue and Calcium Metabolism

Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.

Source record↗

Integrated Resistance and Aerobic Training Study - Sprint

Space flight causes reductions in fitness/health: (1) Cardiovascular -- reduced VO2max, cardiac output (2) Bone -- reduced bone mineral density (3) Muscle -- reduced mass, strength and endurance. Exercise is the primary countermeasure to protect against these changes and was made operational before completely mature. Research continues to identify most effective/efficient exercise programs. Crew medical tests (cardio, muscle, bone) do not yield sufficient information to fine tune the effectiveness of exercise programs, thus there is a need for more detailed testing aimed at identifying the most effective training program. The objective of this program was to obtain detailed information about crew physical fitness pre-and post-flight and evaluate new evidence based exercise prescription with higher intensity, lower duration and frequency.

Ploutz-Snyder, Lori↗

Loading Configurations and Ground Reaction Forces During Treadmill Running in Weightlessness

Studies have shown losses in bone mineral density of 1-2% per month in critical weight bearing areas such as the proximal femur during long-term space flight (Grigoriev, 1998). The astronauts currently onboard the International Space Station (ISS) use a treadmill as an exercise countermeasure to bone loss that occurs as a result of prolonged exposure to weightlessness. A crewmember exercising on the treadmill is attached by a harness and loading device. Ground reaction forces are obtained through the loading device that pulls the crewn1ember towards the treadmill surface during locomotion. McCrory et al. (2002) found that the magnitude of the peak ground reaction force (pGRF) during horizontal suspension running, or simulated weightlessness, was directly related to the load applied to the subject. It is thought that strain magnitude and strain rate affects osteogenesis, and is a function of the magnitude and rate of change of the ground reaction force. While it is not known if a minimum stimulus exists for osteogenesis, it has been hypothesized that in order to replicate the bone formation occurring in normal gravity (1 G), the exercise in weightlessness should mimic the forces that occur on earth. Specifically, the pGRF obtained in weightlessness should be comparable to that achieved in 1 G.

DeWitt, John↗

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.↗

Sensitivity Analysis of the Bone Fracture Risk Model

Introduction: The probability of bone fracture during and after spaceflight is quantified to aid in mission planning, to determine required astronaut fitness standards and training requirements and to inform countermeasure research and design. Probability is quantified with a probabilistic modeling approach where distributions of model parameter values, instead of single deterministic values, capture the parameter variability within the astronaut population and fracture predictions are probability distributions with a mean value and an associated uncertainty. Because of this uncertainty, the model in its current state cannot discern an effect of countermeasures on fracture probability, for example between use and non-use of bisphosphonates or between spaceflight exercise performed with the Advanced Resistive Exercise Device (ARED) or on devices prior to installation of ARED on the International Space Station. This is thought to be due to the inability to measure key contributors to bone strength, for example, geometry and volumetric distributions of bone mass, with areal bone mineral density (BMD) measurement techniques. To further the applicability of model, we performed a parameter sensitivity study aimed at identifying those parameter uncertainties that most effect the model forecasts in order to determine what areas of the model needed enhancements for reducing uncertainty. Methods: The bone fracture risk model (BFxRM), originally published in (Nelson et al) is a probabilistic model that can assess the risk of astronaut bone fracture. This is accomplished by utilizing biomechanical models to assess the applied loads; utilizing models of spaceflight BMD loss in at-risk skeletal locations; quantifying bone strength through a relationship between areal BMD and bone failure load; and relating fracture risk index (FRI), the ratio of applied load to bone strength, to fracture probability. There are many factors associated with these calculations including environmental factors, factors associated with the fall event, mass and anthropometric values of the astronaut, BMD characteristics, characteristics of the relationship between BMD and bone strength and bone fracture characteristics. The uncertainty in these factors is captured through the use of parameter distributions and the fracture predictions are probability distributions with a mean value and an associated uncertainty. To determine parameter sensitivity, a correlation coefficient is found between the sample set of each model parameter and the calculated fracture probabilities. Each parameters contribution to the variance is found by squaring the correlation coefficients, dividing by the sum of the squared correlation coefficients, and multiplying by 100. Results: Sensitivity analyses of BFxRM simulations of preflight, 0 days post-flight and 365 days post-flight falls onto the hip revealed a subset of the twelve factors within the model which cause the most variation in the fracture predictions. These factors include the spring constant used in the hip biomechanical model, the midpoint FRI parameter within the equation used to convert FRI to fracture probability and preflight BMD values. Future work: Plans are underway to update the BFxRM by incorporating bone strength information from finite element models (FEM) into the bone strength portion of the BFxRM. Also, FEM bone strength information along with fracture outcome data will be incorporated into the FRI to fracture probability.

mathematical models↗

Perspective on the impact of weightlessness on calcium and bone metabolism

As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

short duration↗

High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

NASA Discipline Number 26-10↗

Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure

This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month-old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2-induced subperiosteal bone disappeared. In contrast, when PGE2 treatment was stopped and 1 micron risedronate per kg twice a week for 60 days was administered during the maintenance (+/-) phase, the PGE2-induced subperiosteal bone and some of the subendocortical bone and marrow trabeculae persisted.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Discipline Musculoskeletal↗

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

NASA Discipline Musculoskeletal↗

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Spinal Cord Injury↗

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Risk Surveillance↗