Feasibility Study: QCT Modality for Risk Surveillance of Bone - Effects of In-flight Countermeasures on Sub-regions of the Hip Bone (Hip QCT) - 03.25.14
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Feasibility Study: QCT Modality for Risk Surveillance of Bone - Effects of In-flight Countermeasures on Sub-regions of the Hip Bone (Hip QCT) aims to use quantitative computed tomography (QCT) as a surveillance technology to monitor changes in hip bone structure in response to in-flight bone countermeasures. The regions of bone being measured are determinants of fracture risk and will help define the response of hip bone structure to spaceflight, to countermeasures and after return to earth.
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Johnson Space Center, Human Research Program, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
Earth Benefits, Space Exploration
ISS Expedition Duration
March 2013 - October 2015
Previous ISS Missions
This study will share QCT data obtained from on-going ISS investigations: Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss and Sprint integrated Resistance and Aerobic Training Study.
- It needs to be understood if long duration ISS Crewmembers are more susceptible to developing osteoporosis at a younger age because of bone changes that occur during missions in space. Recent research, using an imaging device for the hip called QCT, has described changes in the structure of the hip during spaceflight. This study will describe how those changes in bone structure affect the strength of the hip bone and how losses in hip strength might be prevented or recovered.
- The study will use the QCT instrument at a local hospital to measure hip structure and describe how different types of bone loss countermeasures being tested in space (a drug vs. exercise) change the structure of the hip differently.
- A special software analysis tool will compute the strength of the hip from the QCT measurements. This results will tell us if and how tested countermeasures affect the hip bone strength in space.
Quantitative Computed Tomography [QCT] is a 3-D bone imaging technology that is used typically to scan the hip and spine. QCT is capable of measuring, volumetric bone mineral density [BMD, mg/cm3] of separate cortical and trabecular sub-regions as well as of total (integral) bone. In contrast to the 2-D imaging by dual-energy x-ray absorptiometry [DXA], volumetric QCT at the hip is limited to research applications at this time because there is not enough medical evidence to determine how QCT data should be used in clinical practice. QCT however provides additional information on bone structure and increases the understanding of how bones respond to effectors of bone loss or gain.
A recently convened a panel of clinical bone experts reviewed available medical and research information from astronauts who flew on long-duration space missions. This panel of policy-makers in the osteoporosis field recommended that the trabecular compartment of the hip should be monitored for recovery after return to Earth. Consequently, this study will use preflight and postflight QCT scanning of the hips in ISS astronauts to evaluate the ability of in-flight countermeasures to mitigate declines in the trabecular sub-regions of the hip (total hip, femoral neck and trochanter).
This study further hypothesizes that QCT scanning can distinguish the effects of different categories of in-flight countermeasures/activities on distinct compartments of the hip bone. For example, this pilot study will demonstrate that biochemically-based countermeasures (e.g., the pharmaceutical bisphosphonate agent) will result in a detectable prevention of BMD loss in hip trabecular compartment while biomechanically-based countermeasures (resistive exercise on the Advanced Resistive Exercise Device [ARED]) will induce a detectable expansion of cortical bone apposition - increasing both bone cross-sectional area and integral BMD as a consequence.
These different effects on hip morphology will be subsequently translated to an effect on hip bone strength of the ISS astronaut. The combination of countermeasures that impact both compartments will more likely result in greater hip bone strength -- as estimated by analyzing QCT data by Finite Element Modeling (FEM) - than of any singly applied countermeasure. This assertion will be approached in this pilot study by addressing the following aims in each ISS astronaut: 1) Characterize the response of i) trabecular and cortical BMDs of the hip and ii) cross-sectional areas of cortical bone, trabecular bone and integral bone, to countermeasures that are either based upon biochemistry or mechanical-loading – with QCT measures. 2) Translate the QCT-measured changes in hip bone morphology (Aim 1) to hip bone fracture loads (aka, “hip bone strength”) using FEM. 3) Characterize QCT-measured changes in hip bone morphology (Aim 1) following a 12-month postflight period on earth and, in addition, translate these changes to the percentage recovery of preflight hip bone strength determined by FEM. By addressing these aims, this pilot study of risk surveillance in astronauts using research technologies, will provide preliminary data measuring independent predictors of fracture risk in the aging humans (Black et al, JBMR 2008; Bousson et al JBMR 2011).
The objective surveillance data will help address the following questions: Are in-flight countermeasures and postflight activities sufficient to protect against a decline in hip trabecular BMD? Do countermeasures protect against a decline in hip bone strength? Can hip bone strength be sufficiently recovered with the current, or self-directed, post-mission rehabilitation?
The information collected from this surveillance study will help a clinical advisory panel assess if there is a requirement to prevent early onset osteoporosis in long-duration astronauts, the type of preventative countermeasure, and the optimal timing (preflight, in-flight or postflight) for that countermeasure. The QCT data of hip bone structure, and the estimation of hip bone strength by Finite Element Modeling (FEM), will provide additional characterization on how hip adapts to spaceflight, which will improve the ability to forecast hip fractures, during a mission, by modeling efforts.
This study of younger aged, astronauts will add to a growing population dataset of hip bone strengths, estimated by FEM. FEM-based cut-points for fracture risk are being investigated as an index to assess the efficacy of osteoporosis therapies -- as an alternative to monitoring fracture outcome. This approach may be valuable for the rare, complex subject with bone loss.
Ten subjects are requested to perform the preflight and postflight baseline data collection for Hip QCT. Additionally, data will be collected before and after the yearlong mission of the US crewmember launching on 42S.
This investigation only requires baseline data collection (BDC) both preflight and postflight. No inflight testing will occur.
Ground Based Results Publications
Lang TF, Leblanc AD, Evans HJ, Lu Y. Adaptation of the Proximal Femur to Skeletal Reloading After Long-Duration Spaceflight. Journal of Bone and Mineral Research. 2006; 21(8): 1224-1230.
Lang TF, Leblanc AD, Evans HJ, Lu Y, Genant HK, Yu A. Cortical and Trabecular Bone Mineral Loss from the Spine and Hip in Long-duration Spaceflight. Journal of Bone and Mineral Research. 2004; 19(6): 1006-1012. DOI: 10.1359/JBMR.040307.
Keyak JH, Koyama AK, Leblanc AD, Lu Y, Lang TF. Reduction in proximal femoral strength due to long-duration spaceflight. Bone. 2009; 44(3): 449-453. DOI: 10.1016/j.bone.2008.11.014.
Representative image of a clinical Quantitative Computed Tomography [QCT] instrument (left side) with its capability of detecting the transmission of x-rays in hip bone over three dimensions. Representative QCT scan of hip (right side) with mineral-dense cortical bone in red and the trabecular "spongy" bone compartment in blue. Image courtesy of HRP
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Representative analysis of hip QCT images by Finite Element Modeling. This mathematical model of the 3-D hip structure can be used to calculate the force required to fracture the hip, based upon the 3-D geometry and mechanical properties computed from each astronaut?s QCT bone density. These plots illustrate the von Mises stress distributions in two proximal femora of males representing typical control subjects (left) and fracture subjects (right). Image courtesy of HRP.
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