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At least 19 records

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

OMalley, Bert W.↗

The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise prescriptions on preserving bone. More specifically, the model will accept loading history due to muscle and joint force on bone and produce quantified remodeling within the bone region under influence of the applied stress. Furthermore, because they tend to respond differently, the bone remodeling model includes both trabecular bone and cortical bone.

Pennline, James↗

Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

LeBlanc, Adrian D.↗

Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

Smith, S. M.↗

Biomechanical Modeling of the Deadlift Exercise on the HULK Device to Improve the Efficacy of Resistive Exercise Microgravity Countermeasures

Extended spaceflight typically results in the loss of muscular strength and bone density due to exposure to microgravity. Resistive exercise countermeasures have been developed to maintain musculoskeletal health during spaceflight. The Advanced Resistive Exercise Device (ARED) is the "gold standard" of available devices; however, its footprint and volume are too large for use in space capsules employed in exploration missions. The Hybrid Ultimate Lifting Kit (HULK) device, with its smaller footprint, is a prototype exercise device for exploration missions. This work models the deadlift exercise being performed on the HULK device using biomechanical simulation, with the long-term goal to improve and optimize astronauts' exercise prescriptions, to maximize the benefit of exercise while minimizing time and effort invested.

Countermeasures↗

Effect of a hypergravity environment on cortical bone elasticity in rats

There is considerable interest in determining whether hypergravity can be used as a countermeasure for microgravity-induced bone loss. This study was conducted on 20 immature male rats in order to investigate possible elastic adaptations of cortical bone in rapidly growing rats exposed to chronic hypergravity. Ten rats were continuously centrifuged for 14 days at twice gravitational acceleration (2G) on a 12.75 foot radius centrifuge and 10 rats concurrently acted as stationary controls. The effect of hypergravity on the elastic characteristics of cortical bone was quantified via ultrasonic wave propagation. Propagation velocities of longitudinal and shear waves were measured through cubic cortical specimens from the posterior femoral diaphyses. Density was measured with an Archimedes' technique. The orthotropic elastic properties were calculated and used to compare the difference between groups. Results showed an average increase in both the Young's moduli (Eii, + 2.2%) and shear moduli (Gij, + 4.3%) with a statistically significant increase only in G12 (+15.7%, P = 0.046). The ratio of transverse to axial strain (Poisson's ratio, nuij) demonstrated statistically significant changes in nu12, nu21, nu13, and nu31 (P < 0.05). These findings suggest that although slight elastic changes were incurred via a hypergravity environment, the treatment level or duration in this study do not dramatically perturb the normal elastic behavior of cortical bone and that dramatic biomechanical differences noted in previous studies were due more to structural changes than material elasticity changes. Hypergravity applied post facto to a microgravity environment would offer further illucidation of this method as treatment for a degenerative spaceflight experience.

Non-NASA Center↗

A Biomechanical Approach to Assessing Hip Fracture Risk

Bone loss in microgravity is well documented, but it is difficult to quantify how declines in bone mineral density (BMD) contribute to an astronaut's overall risk of fracture upon return. This study uses a biomechanical approach to assessing hip fracture risk, or Factor of Risk (Phi), which is defined as the ratio of applied load to bone strength. All long-duration NASA astronauts from Expeditions 1-18 were included in this study (n=25), while crewmembers who flew twice (n=2) were treated as separate subjects. Bone strength was estimated based on an empirical relationship between areal BMD at the hip, as measured by DXA, and failure load, as determined by mechanical testing of cadaver femora. Fall load during a sideways fall was calculated from a previously developed biomechanical model, which takes into account body weight, height, gender, and soft tissue thickness overlying the lateral aspect of the hip that serves to attenuate the impact force. While no statistical analyses have been performed yet, preliminary results show that males in this population have a higher FOR than females, with a post- flight Phi of 0.87 and 0.36, respectively. FOR increases 5.1% from preflight to postflight, while only one subject crossed the fracture "threshold" of Phi = 1, for a total of 2 subjects with a postflight Phi > 1. These results suggest that men may be at greater risk for hip fracture due largely in part to their relatively thin soft tissue padding as compared to women, since soft tissue thickness has the highest correlation (R(exp 2)= .53) with FOR of all subject-specific parameters. Future work will investigate changes in FOR during recovery to see if baseline risk levels are restored upon return to 1-g activity. While dual x-ray absorptiometry (DXA) is the most commonly used clinical measure of bone health, it fails to provide compartment-specific information that is useful in assessing changes to bone quality as a result of microgravity exposure. Peripheral quantitative computed tomography (pQCT) accomplishes this by imaging transverse "slices" of the long bones. This project was a re-analysis of a 90 day bed rest study to determine if changes to cortical and trabecular compartments could be detected in the distal tibia with statistical significance using a new pQCT image analysis method. Nearly all changes in bone mineral density (BMD) and cross sectional area (CSA) measures were seen with statistical significance, with the exception of a change in cortical BMD. Total bone CSA increased by 1.1 % (p =0.01), cortical CSA decreased by - 5.6% (p<0.001) and trabecular CSA increased by 1.76% (p=0.007); the combination of which suggests bone resorption occurred at the endocortical surface in response to mechanical unloading by bed rest. Furthermore, total BMD and trabecular BMD decreased (-3.8%, p=0.001 and -2.8%, p =0.007, respectively), while decreases in cortical BMD failed to reach significance (-1.2%, p=0.07). Given that compartment-specific changes are seen with significance and are likely to influence bone strength, it is recommended that pQCT remain a standard measure used in bed rest because it provides a unique measure by which to better evaluate the efficacy of countermeasures to microgravity-induced bone loss.

Ellman, Rachel↗

Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bedrest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Schepelmann, Alexander↗

Overview and Evaluation of a Computational Bone Physiology Modeling Toolchain and Its Application to Testing of Exercise Countermeasures

Prolonged microgravity exposure disrupts natural bone remodeling processes and can lead to a significant loss of bone strength, increasing injury risk during missions and placing astronauts at a greater risk of bone fracture later in life. Resistance-based exercise during missions is used to combat bone loss, but current exercise countermeasures do not completely mitigate the effects of microgravity. To address this concern, we present work to develop a personalizable, site-specific computational modeling toolchain of bone remodeling dynamics to understand and estimate changes in volumetric bone mineral density (BMD) in response to microgravity-induced bone unloading and in-flight exercise. The toolchain is evaluated against data collected from subjects in a 70-day bed rest study and is found to provide insight into the amount of exercise stimulus needed to minimize bone loss, quantitatively predicting post-study volumetric BMD of control subjects who did not perform exercise, and qualitatively predicting the effects of exercise. Results suggest that, with additional data, the toolchain could be improved to aid in developing customized in-flight exercise regimens and predict exercise effectiveness.

Schepelmann, Alexander↗

Candidate Nutritional Countermeasure to Mitigate Adverse Effects of Spaceflight

Problem statement: During spaceflight, astronauts are subjected to microgravity as well as radiation, both of which have adverse effects on bones, soft tissues and organs, possibly by shared mechanisms. For this reason there is a need to identify broad-spectrum countermeasures to protect multiple tissues from both insults.6.The spaceflight environment poses multiple challenges to homeostasis, including microgravity and ionizing radiation. Together, these factors contribute to cellular stress, and effects include increased generation of reactive oxygen species (ROS), oxidative and DNA damage, cell cycle arrest and cell senescence. We have shown that a purified diet supplemented with dried plum (DP, 25) conferred full protection of cancellous structure from the rapid bone loss caused by exposure to ionizing radiation (Schreurs et al. 2016). Based on these promising results for a new countermeasure to prevent space radiation induced-tissue damage, we will conduct additional studies to advance the potential countermeasure to a higher CRL level. We will test the DP diet for its ability to prevent bone loss caused by simulated microgravity as well as exposure to radiation. This will be achieved by exposing mice to each factor (simulated microgravity and radiation) alone and in combination. We hypothesize that spaceflight conditions lead to oxidative damage and bone loss, and that DP, a dietary additive rich in antioxidant and polyphenolic compounds, is an effective countermeasure for multiple tissues, including bone. To test this hypothesis we will accomplish the following aims: Aim 1 Determine if the antioxidant rich diet DP prevents simulated microgravity-induced bone loss. Aim 2 Determine if DP prevents simulated spaceflight-induced bone loss (microgravity and radiation combined). Aim 3 Determine if DP is effective as a countermeasure for adverse effects of simulated microgravity and radiation on non-skeletal tissues (brain, eye).

Schreurs, Ann-Sofie↗

Precision bone and muscle loss measurements by advanced, multiple projection DEXA (AMPDXA) techniques for spaceflight applications

An advanced, multiple projection, dual energy x-ray absorptiometry (AMPDXA) scanner system is under development. The AMPDXA is designed to make precision bone and muscle loss measurements necessary to determine the deleterious effects of microgravity on astronauts as well as develop countermeasures to stem their bone and muscle loss. To date, a full size test system has been developed to verify principles and the results of computer simulations. Results indicate that accurate predictions of bone mechanical properties can be determined from as few as three projections, while more projections are needed for a complete, three-dimensional reconstruction. c 2001. Elsevier Science Ltd. All rights reserved.

NASA Discipline Life Sciences Technologies↗

Artificial Gravity: Effects on Bone Turnover

The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

Heer, M.↗

A method to determine the kinematics of the lower limbs of a subject pedaling a bicycle using encoders and accelerometers

The goal of this research was to determine kinematic parameters of the lower limbs of a subject pedaling a bicycle. An existing measurement system was used as the basis to develop the model to determine position and acceleration of the limbs. The system consists of an ergometer instrumented to provide position of the pedal (foot), accelerometers to be attached to the lower limbs to measure accelerations, a recorder used for filtering, and a computer instrumented with an A/D board and a decoder board. The system is designed to read and record data from accelerometers and encoders. Software has been developed for data collection, analysis and presentation. Based on the measurement system, a two dimensional analytical model has been developed to determine configuration (position, orientation) and kinematics (velocities, accelerations). The model has been implemented in software and verified by simulation. An error analysis to determine the system's accuracy shows that the expected error is well within the specifications of practical applications. When the physical hardware is completed, NASA researchers hope to use the system developed to determine forces exerted by muscles and forces at articulations. This data will be useful in the development of countermeasures to minimize bone loss experienced by astronauts in microgravity conditions.

Liu, Shih-Ching↗

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.↗

Quantifying Biomechanical Characteristics of Jumping Exercises in 1G and in Simulated and True Microgravity

Exercise in microgravity is one of the most promising countermeasures to the dual problems of space flight-induced bone loss and muscle atrophy. Although exercise in microgravity has been studied extensively from a metabolic standpoint, little research has focused on the efficacy of different forms of exercise for maintaining musculoskeletal integrity. Exercise protocols have not been effective in preventing muscle atrophy and bone loss during space flight, especially in the lower extremities. In 1-G, however, animal experiments have clearly indicated that: (1) certain bone strains and strain rates do stimulate bone deposition, and (2) repetitive loading of the lower extremity can increase osteonal bone formation even as proximally as the vertebral column. Such studies have also indicated that a relatively small number of appropriate loading cycles may lead to bone deposition. This suggests that an optimal exercise regimen might be able to maintain bone and muscle integrity during space flight. Since there is evidence that the bones and muscles of the lower limbs are particularly affected by space flight, the present study addressed two major aims: (1) quantify externally applied impact loads and rates of loading under the feet during tethered jumping exercises, and (2) determine the amount of eccentric and concentric whole-muscle activity during these jumping exercises in true and in simulated zero-gravity.

Davis, B. L.↗

Exploration Exercise System (EES) Development

Exploration class missions will be required to have an exercise device that is lightweight, has a small footprint, and is capable of providing enough physical stimulus and exercise variability to be an effective countermeasure against muscle and bone loss that results from the microgravity environment. Exploration exercise device prototypes should be evaluated on the ground and in-orbit for feasibility of use in microgravity for long and short duration exploration missions and efficacy of the device to maintain multi-system health and performance. The European Enhanced Exploration Exercise Device (E4D) was selected as the exploration prototype device to be evaluated on ISS for efficacy and feasibility of use as a single multi-modality device for the exercise system for exploration missions. This effort supports the continued development, testing, and verification of E4D hardware and software, internal NASA integration (Human Health and Performance, ISS Vehicle Office, Engineering, and Flight Operations), and external integration across NASA, ESA, and the Danish Aerospace Company (DAC). Providing a feasibility and acceptability assessment from a physiological efficacy and hardware durability standpoint are critical for informing use and risk associated with use on exploration missions. Clearly defined objectives from end users, stakeholders, and Subject Matter Experts (SMEs) will be tested by crewmembers during acute use sessions and long duration use of the exercise device while on ISS. This effort will include a flight study where crewmembers will be asked to exercise using only the E4D during the duration of their mission and participate in a battery of physiological testing to evaluate the efficacy. Hardware is scheduled to launch in FY25 followed by 2 years of operational use after activation and checkout. A final recommendation will be provided to the Artemis program on acceptability of the device for exploration missions. The E4D needs a vibration isolation stabilization (VIS) system that serves as a platform for the exercise hardware to protect the vehicle from loads imparted during exercise. Exploration forward VIS systems will need to protect the vehicle and provide sufficient stabilization for the exerciser during performance of all critical exercises. These enabling capabilities need to be achieved within exploration vehicle power, thermal, mass, and volume limitations.

Kent Lawrence Kalogera↗

Trabecular Bone Mechanical Properties and Fractal Dimension

Countermeasures for reducing bone loss and muscle atrophy due to extended exposure to the microgravity environment of space are continuing to be developed and improved. An important component of this effort is finite element modeling of the lower extremity and spinal column. These models will permit analysis and evaluation specific to each individual and thereby provide more efficient and effective exercise protocols. Inflight countermeasures and post-flight rehabilitation can then be customized and targeted on a case-by-case basis. Recent Summer Faculty Fellowship participants have focused upon finite element mesh generation, muscle force estimation, and fractal calculations of trabecular bone microstructure. Methods have been developed for generating the three-dimensional geometry of the femur from serial section magnetic resonance images (MRI). The use of MRI as an imaging modality avoids excessive exposure to radiation associated with X-ray based methods. These images can also detect trabecular bone microstructure and architecture. The goal of the current research is to determine the degree to which the fractal dimension of trabecular architecture can be used to predict the mechanical properties of trabecular bone tissue. The elastic modulus and the ultimate strength (or strain) can then be estimated from non-invasive, non-radiating imaging and incorporated into the finite element models to more accurately represent the bone tissue of each individual of interest. Trabecular bone specimens from the proximal tibia are being studied in this first phase of the work. Detailed protocols and procedures have been developed for carrying test specimens through all of the steps of a multi-faceted test program. The test program begins with MRI and X-ray imaging of the whole bones before excising a smaller workpiece from the proximal tibia region. High resolution MRI scans are then made and the piece further cut into slabs (roughly 1 cm thick). The slabs are X-rayed again and also scanned using dual-energy X-ray absorptiometry (DEXA). Cube specimens are then cut from the slabs and tested mechanically in compression. Correlations between mechanical properties and fractal dimension will then be examined to assess and quantify the predictive capability of the fractal calculations.

Hogan, Harry A.↗