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NASA NTRS2002

Core Research Program, Year 5

Dramatic losses of bone mineral density (BMD) and muscle strength are two of the best documented changes observed in humans after prolonged exposure to microgravity. Recovery of muscle upon return to a 1-G environment is well studied, however, far less is known about the rate and completeness of BMD recovery to pre-flight values. Using the mature tail-suspended adult rat model, this proposal will focus on the temporal course of recovery in tibial bone following a 28-d period of skeletal unloading. Through the study of bone density and muscle strength in the same animal, time-points during recovery from simulated microgravity will be identified when bone is at an elevated risk for fracture. These will occur due to the rapid recovery of muscle strength coupled with a slower recovery of bone, producing a significant mismatch in functional strength of these two tissues. Once the time-point of maximal mismatch is defined, various mechanical and pharmacological interventions will be tested at and around this time-point in attempt to minimize the functional difference of bone and muscle. The outcomes of this research will have high relevance for optimizing the rehabilitation of astronauts upon return to Earth, as well as upon landing on the Martian surface before assuming arduous physical tasks. Further. it will impact significantly on rehabilitation issues common to patients experiencing long periods of limb immobilization or bed rest.

Source record↗

NASA NTRS2004

Response Of Mineralizing And Non-Mineralizing Bone Cells To Fluid Flow: An In Vitro Model For Mechanotransruction

Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in osteoblasts, including increased proliferation, osteoblastic differentiation, alkaline phosphatase activity, and production of nitric oxide, prostaglandins, and osteopontin. Several proteins have been implicated in osteoblastic mechanotransduction including Bone Morphogenetic Protein-2 (BMP-2), parathyroid hormone, 1,25-dihydroxyvitamin D3 receptor, osteopontin (OPN), osteoprotegerin (OPG), and alkaline phosphatase (AP). We will characterize relative levels of each protein in mineralizing or non-mineralizing MC3T3 osteoblastic cells that have been exposed to fluid flow compared to non-fluid flow using immunofluorescent staining and two- photon laser microscopy as well as western blotting. Because calcium-mediated pathways are important in osteoblastic signaling, we will transfect MC3T3 cells with cameleon probes for Ca2+ containing YFP and CFP. Results will be analyzed using FRET/FLIM to study differential release of intracellular Ca(2+) in response to fluid flow and conditions inducing matrix mineralization. In addition, we plan to conduct several microarray experiments to determine differential gene expression in MC3T3 cells in response to fluid flow and conditions inducing mineralization.

Makuch, Lauren A.↗

NASA NTRS2004

Space flight and bone formation

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Non-NASA Center↗

NASA NTRS2017

The Role of Nuclear Cytoskeleton in the Osteocytic Response to Simulated Weightlessness

While in space, astronauts exercise frequently to combat bone and muscle loss due to weightlessness. This loss in bone can lead to serious health problems, such as increased fracture risk. Osteocytes are known to play a vital role in bone resorption and formation. It is also theorized that osteocytes act as the mechanosensors of bone, detecting mechanical stimulus and relaying these signals to surrounding cells. Previous research suggests that, during space flight, osteocytes exhibit matrix remodeling and resorption capabilities (osteocytic osteolysis) leading to an enlargement of the lacunae and contributing to overall bone degradation. The intercellular causes of these changes has not yet been determined. LINC or Linker of Nucleoskeleton and Cytoskeleton is a protein complex that forms a connection between the nucleus and cytoskeleton. LINC serves as a way to transmit mechanical signals to the nucleus and is also involved in the regulation of Wnt signaling via KASH proteins (Nesprin -1 and Nesprin -2). Wnt signaling in osteocytes assists with bone homeostasis and perturbed Wnt signaling can lead to bone loss. This suggests that LINC may contribute to the bone diminishing effects of microgravity. Therefore, we hypothesize that the disruption of LINC or LINC components by simulated microgravity (using the hindlimb unloading model, HU) affects Wnt signaling in osteocytes affecting bone formation and leading to increased osteocyte lacunar size. To test these hypotheses, we plan to conduct an animal study using 16 week old male mice (n6group). The mice will undergo HU for up to 7 days. After the desired time point, we will utilize quantitative real-time PCR techniques to determine the changes in gene expression of seven LINC complex genes (Sun -1, Sun -2, Nesprin -1, Nesprin -2, Lamin AC, Lamin B, and Emerin) and genes related to bone formation and osteocyte signaling. To determine changes osteocytic remodeling activity we will immunostain for osteocyte markers (Dmp-1 and Sost) and osteolysis markers (TRAP, MMPs) and measure lacunar size.

Touchstone, Hallie↗

NASA NTRS2013

Clinical Practice Guideline for Vitamin D

Vitamin D and its metabolites have clinical significance because they play a critical function in calcium homeostasis and bone metabolism. Although not all of the pathologic mechanisms have been adequately described, vitamin D insufficiency and deficiency, as measured by low levels of 25-OH vitamin D, are associated with a variety of clinical conditions including osteoporosis, falls and fractures in the elderly, decreased immune function, bone pain, and possibly colon cancer and cardiovascular health.2 Apart from inadequate dietary intake, patients may present with low levels of vitamin D if they receive inadequate sunlight. The astronaut population is potentially vulnerable to low levels of vitamin D for several reasons. Firstly, they may train for long periods in Star City, Russia, which by virtue of its northern latitude receives less sunlight in winter months. Secondly, astronauts are deprived of sunlight while aboard the International Space Station (ISS). In addition, ISS crew members are exposed to microgravity for prolonged durations and are likely to develop low bone mineral density despite the use of countermeasures. Therefore, closely monitoring and maintaining adequate vitamin D levels is important for the astronaut corps.

Tarver, William J.↗

NASA NTRSDate not supplied

Increased Rates of Hip and Spine Fractures in Astronauts are Associated with Longer Spaceflight Durations

Given the accelerated declines in bone mineral density reported in US astronauts serving on the International Space Station, there is a possibility that a prolonged exposure to spaceflight could put astronauts at increased fracture risk during subsequent planetary explorations or after return to Earth. To date, there have been no fractures in astronauts during spaceflight. Recently-reported data from a flight study suggested that intake of the bisphosphonate alendronate combined with resistive exercise (on the Advanced Resistive Exercise Device – ARED) preserved more astronauts at their preflight skeletal status after a ~6-mos spaceflight than with ARED exercise alone. However, there is low acceptance of alendronate, or the recommended zoledronic acid, to suppress in-flight bone loss largely due to concern for unintended medication side effects and a perceived absence of astronaut fractures that can be directly attributable to spaceflight exposure. Hence, a recent survey of all astronaut fractures was analyzed to assess whether the rate of postflight fractures could be associated with extended spaceflight exposures. The fracture survey was of 262 astronauts across 8433.6 person-years (PY) and grouped according to previous exposure to a “Long Duration (LD)” spaceflight (3 mos or greater, but typically 6-mos). The number of fractures was modeled using count regression adjusting for i) the repeated measures within individuals across the groups, ii) the differing length of surveillance for each individual and iii) age at start of surveillance for each of the groups. Astronaut Group by Spaceflight Exposure #Individuals PY Covered No Exposure to Spaceflight 262 1882.7 No Exposure to LD spaceflight “Non-LD” 232 6121.3 Exposure to LD spaceflight 42 429.6 Analysis revealed an increased rate of hip and spine fractures for surveillance periods compared between LD Exposure and Non-LD Exposure: Hip – Relative Rate: 3.4 (95%CI: 1.0, 12.0); Spine– Relative Rate: 3.4 (95%CI: 1.0, 11.6). For all other skeletal sites, rates of fracture were similar for LD and Non-LD exposures. Data comparisons were conducted between groups of astronauts to preclude the interpretation of greater physical activity in astronauts as a contributing factor to fracture rates. This analysis of fracture data is the first report associating postflight hip and spine fractures in astronauts with exposure to extended duration spaceflights. Further analyses integrating co-morbidities for bone loss are planned.

skeleton↗

NASA NTRS2012

Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

Weightlessness causes a cephalad fluid shift and reduction in mechanical stimulation, adversely affecting both cortical and trabecular bone tissue in astronauts. In rodent models of weightlessness, the onset of bone loss correlates with reduced skeletal perfusion, reduced and rarified vasculature and lessened vasodilation, which resembles blood-bone symbiotic events that can occur with fracture repair and aging. These are especially serious risks for long term, exploration class missions when astronauts will face the challenge of increased exposure to space radiation and abrupt transitions between different gravity environments upon arrival and return. Previously, we found using the mouse hindlimb unloading model and exposure to heavy ion radiation, both disuse and irradiation cause an acute bone loss that was associated with a reduced capacity to produce bone-forming osteoblasts from the bone marrow. Together, these findings led us to hypothesize that exposure to space radiation exacerbates weightlessness-induced bone loss and impairs recovery upon return, and that treatment with anti-oxidants may mitigate these effects. The specific aims of this recently awarded grant are to: AIM 1 Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress. AIM 2 Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction. AIM 3 Determine how space radiation influences later skeletal and vasculature recovery from prolonged weightlessness and the potential of anti-oxidants to preserve adaptive remodeling.

Alwood, J. S.↗

NASA NTRS1995

Current methods and advances in bone densitometry

Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis.

Review, Academic↗

NASA NTRS2017

Characterizing Fractures Across the Astronaut Corps: Preliminary Findings from Population-Level Analysis

Despite evidence of bone loss during spaceflight and the implementation of countermeasures to mitigate this loss, the subsequent risk of fracture among astronauts is not known. Multiple factors such as age, sex, fracture history, and others may combine to increase fracture risk. The purpose of this study was to describe fractures among the astronaut population and generate questions for future occupational surveillance studies.

Rossi, Meredith M.↗

NASA NTRS2014

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means.

Sibonga, Jean D.↗

NASA NTRS2016

Recommended Methods for Monitoring Skeletal Health in Astronauts to Distinguish Specific Effects of Prolonged Spaceflight

NASA uses areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) to monitor skeletal health in astronauts after typical 180-day spaceflights. The osteoporosis field and NASA, however, recognize the insufficiency of DXA aBMD as a sole surrogate for fracture risk. This is an even greater concern for NASA as it attempts to expand fracture risk assessment in astronauts, given the complicated nature of spaceflight-induced bone changes and the fact that multiple 1-year missions are planned. In the past decade, emerging analyses for additional surrogates have been tested in clinical trials; the potential use of these technologies to monitor the biomechanical integrity of the astronaut skeleton will be presented. OVERVIEW: An advisory panel of osteoporosis policy-makers provided NASA with an evidence-based assessment of astronaut biomedical and research data. The panel concluded that spaceflight and terrestrial bone loss have significant differences and certain factors may predispose astronauts to premature fractures. Based on these concerns, a proposed surveillance program is presented which a) uses Quantitative Computed Tomography (QCT) scans of the hip to monitor the recovery of spaceflight-induced deficits in trabecular BMD by 2 years after return, b) develops Finite Element Models [FEM] of QCT data to evaluate spaceflight effect on calculated hip bone strength and c) generates Trabecular Bone Score [TBS] from serial DXA scans of the lumbar spine to evaluate the effect of age, spaceflight and countermeasures on this novel index of bone microarchitecture. SIGNIFICANCE: DXA aBMD is a widely-applied, evidence-based predictor for fractures but not applicable as a fracture surrogate for premenopausal females and males <50 years. Its inability to detect structural parameters is a limitation for assessing changes in bone integrity with and without countermeasures. Collective use of aBMD, TBS, QCT, and FEM analysis for astronaut surveillance could accommodate NASA's aggressive schedule for risk definition and inform a NASA-developed model which assesses the probability of overloading bones during mechanically-loaded mission tasks and possibly for physical activities after return to Earth.

Vasadi, Lukas J.↗

NASA NTRS2018

Ionizing Radiation from Ex Vivo Sterilization Diminishes Collagen Integrity and Vertebral Body Mechanics

Clinical exposure to ionizing radiation could put cancer radiotherapy or bone allograft patients at an increased risk of fracture. In these applications, ionizing radiation levels can range from accumulative 50 Gy for radiotherapy cancer treatment, to acute 35,000 Gy for allograft sterilization. Ionizing radiation has been shown to decrease bon equality through reduced strength and post-yield properties and degrade collagen integrity through either increased crosslinks (advanced glycation end products, AGEs)or fragmentation. It is unclear which collagen structural change accounts for reduced strength. The dose-dependent effect of ionizing radiation on mechanical and biochemical properties of whole bones are not well understood, particularly for ex vivo doses ranging from 50 to 35,000 Gy.

Radiation↗

NASA NTRS2015

Bone Loss During Spaceflight: Available Models and Counter-Measures

There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground analogs to experiments on the ISS. With regards to testing, further evaluation to determine the association between non-invasive tests and fracture during and after spaceflight needs to be performed.

Morris, Jonathan↗

NASA NTRS1999

Skeletal Structural Consequences of Reduced Gravity Environments

The overall goal of this project is to provide structurally meaningful data on bone loss after exposure to reduced gravity environments so that more precise estimates of fracture risk and the effectiveness of countermeasures in reducing fracture risk can be developed. The project has three major components: (1) measure structural changes in the limb bones of rats subjected to complete and partial nonweightbearing, with and without treatment with ibandronate and periodic full weightbearing; (2) measure structural changes in the limb bones of human bedrest subjects, with and without treatment with alendronate and resistive exercise, and Russian cosmonauts flying on the Mir Space Station; and (3) validate and extend the 2-dimensional structural analyses currently possible in the second project component (bedrest and Mir subjects) using 3-dimensional finite element modeling techniques, and determine actual fracture-producing loads on earth and in space.

Ruff, Christropher B.↗

NASA NTRS2014

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long-Duration Astronauts

Bone loss due to long‐duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight‐induced changes in bone mineral density (BMD) and structure result in increased fracture incidence. NASA astronauts currently fly 5 to 6‐month missions on the International Space Station (ISS) and at least one 12‐month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT) and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone micro‐architecture from lumbar spine (LS). DXA scans are routinely performed pre‐ and postflight on all ISS astronauts to follow BMD changes associated with spaceflight. Trabecular Bone Score (TBS) is a relatively new method that measures grey‐scale‐level texture information extracted from LS DXA images and correlates with 3D parameters of bone micro‐architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: Lumbar Spine (L1‐4) DXA scans from 51 astronauts (mean age, 47 +/- 4 yrs) were divided into 3 groups based on the exercise regimens performed onboard the ISS. "Pre‐ARED" (exercise using a load‐limited resistive exercise device, <300 lb), "ARED" (exercise with a high‐load resistive exercise device, up to 600 lb) and "Bisphos+ARED" group (ARED exercise and a 70‐mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre‐ and post‐flight scans. LSC for the LS in our laboratory is 0.025 g/sq. cm. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. Data were analyzed using a paired, 2‐tailed Student's t‐test for the difference between pre‐ and postflight means. Percent change and % change per month are noted. Interpretation: Our data suggest that: TBS and DXA both detected significant decrements in the LS in these pre‐ ARED astronauts, not unexpected given the insufficient loads provided by this early exercise device. TBS did not detect significant changes in the ARED or Bisphos+ARED groups while DXA did detect significant changes in the ARED astronauts. These findings suggest that DXA and TBS are detecting independent effects of bone loss interventions tested in ISS astronauts in space, which may be due to distinct effects of interventions on mineral content of separate cortical vs. trabecular bone. Conclusion: TBS, in conjunction with DXA BMD, may provide additional insight into the nature of changes (or lack thereof) in the microstructure of trabecular bone and the areal BMD of vertebral bodies.

Smith, Scott A.↗

NASA NTRS1974

Internal tibial torsion correction study

A quantitative study of internal torsion in the entire tibial bone was performed by using strain gauges to measure the amount of deformation occuring at different locations. Comparison of strain measurements with physical dimensions of the bone produced the modulus of rigidity and its behavior under increased torque. Computerized analysis of the stress distribution shows that more strain occurs near the torqued ends of the bones where also most of the twisting and fracturing takes place.

Cantu, J. M.↗

NASA NTRS2025

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↗

NASA NTRS2025

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

Risk Surveillance↗