Improving Bone-Health Monitoring in Astronauts: Recommended Use of Quantitative Computed Tomography [QCT] for Clinical and Operational Decisions by NASA

DXA measurement of areal bone mineral density [aBMD,g/cm2] is required by NASA for assessing skeletal integrity in astronauts. Due to the abundance of population-based data that correlate hip and spine BMDs to fragility fractures, BMD is widely applied as a predictor of fractures in the general aging population. In contrast, QCT is primarily a research technology that measures three-dimensional , volumetric BMD (vBMD,mg/cm3) of bone and is therefore capable of differentiating between cortical and trabecular components. Additionally, when combined with Finite Element Modeling [FEM], a computational tool, QCT data can be used to estimate the whole bone strength of the hip [FE strength] for a specific load vector. A recent report demonstrated that aBMD failed to correlate with incurred changes in FE strength (for fall and stance loading) by astronauts over typical 180-day ISS (International Space Station) missions. While there are no current guidelines for using QCT data in clinical practice, QCT increases the understanding of how bone structure and mineral content are affected by spaceflight and recovery on Earth. In order to understand/promote/consider the use of QCT, NASA convened a panel of clinicians specializing in osteoporosis. After reviewing the available, albeit limited, medical and research information from long-duration astronauts (e.g., data from DXA, QCT, FEM, biochemistry analyses, medical records and in-flight exercise performance) the panelists were charged with recommending how current and future research data and analyses could inform clinical and operational decisions. The Panel recommended that clinical bone tests on astronauts should include QCT (hip and lumbar spine) for occupational risk surveillance and for the estimation of whole hip bone strength as derived by FEM. FE strength will provide an improved index that NASA could use to select astronauts of optimal bone health for extended duration missions, for repeat missions or for specific mission operations

Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an applicant for astronaut candidacy, b) Qualify an astronaut for a long-duration (LD) mission, c) Qualify a veteran LD astronaut for a second LD mission, and d) Establish a non-permissible, minimum hip strength following a given mission architecture. This abstract will present the FE-based standards accepted by the FE Strength Task Group for its recommendation to HHC in January 2015

Bone Density Following Three Years of Recovery from Long-Duration Space Flight

It is well recognized that bone mineral density [BMD] at load-bearing sites of the hip and spine sustain significant loss during space flight, estimated at approximately 0.5-1.0% per month. However, the long-term effects on bone health following return from long-duration space flight remain unclear. It is unknown whether BMD for men recovers beyond 1 year following return from space to what would be predicted or if deficits persist. Using our previously created prediction models, we compared the observed BMD of male US crew following 3 years since returning from longduration space flight with what would be predicted if they had not been exposed to microgravity

ISS Squat and Deadlift Kinematics on the Advanced Resistive Exercise Device

Visual assessment of exercise form on the Advanced Resistive Exercise Device (ARED) on orbit is difficult due to the motion of the entire device on its Vibration Isolation System (VIS). The VIS allows for two degrees of device translational motion, and one degree of rotational motion. In order to minimize the forces that the VIS must damp in these planes of motion, the floor of the ARED moves as well during exercise to reduce changes in the center of mass of the system. To help trainers and other exercise personnel better assess squat and deadlift form a tool was developed that removes the VIS motion and creates a stick figure video of the exerciser. Another goal of the study was to determine whether any useful kinematic information could be obtained from just a single camera. Finally, the use of these data may aid in the interpretation of QCT hip structure data in response to ARED exercises performed in-flight. After obtaining informed consent, four International Space Station (ISS) crewmembers participated in this investigation. Exercise was videotaped using a single camera positioned to view the side of the crewmember during exercise on the ARED. One crewmember wore reflective tape on the toe, heel, ankle, knee, hip, and shoulder joints. This technique was not available for the other three crewmembers, so joint locations were assessed and digitized frame-by-frame by lab personnel. A custom Matlab program was used to assign two-dimensional coordinates to the joint locations throughout exercise. A second custom Matlab program was used to scale the data, calculate joint angles, estimate the foot center of pressure (COP), approximate normal and shear loads, and to create the VIS motion-corrected stick figure videos. Kinematics for the squat and deadlift vary considerably for the four crewmembers in this investigation. Some have very shallow knee and hip angles, and others have quite large ranges of motion at these joints. Joint angle analysis showed that crewmembers do not return to a normal upright stance during squat, but remain somewhat bent at the hips. COP excursions were quite large during these exercises covering the entire length of the base of support in most cases. Anterior-posterior shear was very pronounced at the bottom of the squat and deadlift correlating with a COP shift to the toes at this part of the exercise. The stick figure videos showing a feet fixed reference frame have made it visually much easier for exercise personnel and trainers to assess exercise kinematics. Not returning to fully upright, hips extended position during squat exercises could have implications for the amount of load that is transmitted axially along the skeleton. The estimated shear loads observed in these crewmembers, along with a concomitant reduction in normal force, may also affect bone loading. The increased shear is likely due to the surprisingly large deviations in COP. Since the footplate on ARED moves along an arced path, much of the squat and deadlift movement is occurring on a tilted foot surface. This leads to COP movements away from the heel. The combination of observed kinematics and estimated kinetics make squat and deadlift exercises on the ARED distinctly different from their ground-based counterparts. CONCLUSION This investigation showed that some useful exercise information can be obtained at low cost, using a single video camera that is readily available on ISS. Squat and deadlift kinematics on the ISS ARED differ from ground-based ARED exercise. The amount of COP shift during these exercises sometimes approaches the limit of stability leading to modifications in the kinematics. The COP movement and altered kinematics likely reduce the bone loading experienced during these exercises. Further, the stick figure videos may prove to be a useful tool in assisting trainers to identify exercise form and make suggestions for improvement

Bone Density Following Three Years of Recovery from Long-Duration Space-Flight

Bone loss during long-duration space flight is well recognized, but the long-term implications on bone health following return from flight remain unclear. Among US crew who were involved in long-duration missions in space (Mir and ISS), we have previously shown that at approximately 12 months following return, men, but not women, had BMD values at most sites that were still lower than would be expected had they not been exposed to a prolonged period of microgravity. We now extend our observations to 3 years of follow-up post-flight. Using their age, pre-flight BMD and follow-up time, post-flight BMD values for each US crew were predicted based on the model developed from the community sample. We found BMD measures to be either stable or improve by 3 years relative to their immediate post-flight BMD, however only total hip BMD still remains significantly lower than would be expected had they not been exposed to microgravity. Among male US crew, who have had their BMD measured following at least 3 years of recovery post long-duration flight, they continue to have lower BMD at the hip than would be expected, raising potential concerns regarding future hip fracture risk

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2

Does Short Duration Space Flight have a Negative Effect on Bone Density?

No abstract availabl

Bone Health Monitoring in Astronauts: Recommended Use of Quantitative Computed Tomography [QCT] for Clinical and Operational Decisions

This slide presentation reviews the concerns that astronauts in long duration flights might have a greater risk of bone fracture as they age than the general population. A panel of experts was convened to review the information and recommend mechanisms to monitor the health of bones in astronauts. The use of Quantitative Computed Tomography (QCT) scans for risk surveillance to detect the clinical trigger and to inform countermeasure evaluation is reviewed. An added benefit of QCT is that it facilitates an individualized estimation of bone strength by Finite Element Modeling (FEM), that can inform approaches for bone rehabilitation. The use of FEM is reviewed as a process that arrives at a composite number to estimate bone strength, because it integrates multiple factors

Bone Density Following Long Duration Space Flight and Recovery

At approx.12 months, Bone Mineral Density (BMD) at most sites in men remained lower than would be predicted, raising concerns for long-term bone health consequences following space flight. Additional analyses based on longer follow-up are being conducted. Although the N is too small for definitive conclusions, women had lower rates of loss at load-bearing sites of the hip and spine immediately post-flight relative to men and smaller differences between observed vs. predicted BMD at most sites, both immediately and 12 months post-flight, relative to men. The role of other exposures/risk factors need to be explored to further understand these possible gender differences in BMD loss and recovery following long-duration space flight

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS mission, DXA BMD and TBS are detecting different effects of ARED exercise and of ARED + Bisphosphonate on the lumbar spine of astronauts. There is emerging evidence associating reduced TBS with terrestrial metabolic bone disorders where a TBS 1.350 is associated with "normal." However, it is not possible to conclude how the spaceflight-induced changes in TBS increase risk for vertebral fractures in the astronaut or if changes in body composition of the trunk region could be an indirect method of assessing exercise effect on bone microarchitecture. More importantly, this pilot analysis demonstrates a new, minimal risk approach for monitoring changes to vertebral bone microarchitecture. This method could help assess the combined skeletal effects of spaceflight with the effects of aging in the astronaut after return to Earth