Using Dense Phenotyping and Cluster Analysis to Identify Subgroups Associated with Deconditioning in Bed Rest
No abstract available
Mercaldo, Sarah↗
Engineering topics
Spector, Elisabeth
Publications and source records attributed to Spector, Elisabeth.
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.↗
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.↗
Update of the Bisphosphonate ISS Flight Experiment
The bisphosphonate study is an international collaboration between the NASA and JAXA space agencies to investigate the potential value of antiresorptive drugs to mitigate the well-established bone changes associated with long-duration spaceflight. Our hypothesis is that an antiresorptive drug in combination with in-flight exercise will ameliorate bone loss and hypercalcuria during long-duration spaceflight. We have completed data analysis for 7 crewmembers treated with alendronate during flight and 3 of 10 controls without treatment. We previously reported the pre/postflight changes in bone density and the pre versus in-flight changes in various biomarkers in crewmembers taking alendronate during flight. The purpose of this report is to compare these results with the 12- month follow-up data. The table below presents these data as a percentage change from baseline either immediately postflight or in-flight (biochemical markers) with a 1-year follow-up.
LeBlanc, Adrian↗
Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss
Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.
LeBlanc, Adrian↗
C-9 and Other Microgravity Simulations
This document represents a summary of medical and scientific evaluations conducted aboard the C-9 and other NASA-sponsored aircraft from June 2008 to June 2009. Included is a general overview of investigations manifested and coordinated by the Human Adaptation and Counter-measures Division. A collection of brief reports that describe tests conducted aboard the NASA-sponsored aircraft follows the overview. Principal investigators and test engineers contributed significantly to the content of the report, describing their particular experiment or hardware evaluation. Although this document follows general guidelines, each report format may vary to accommodate differences in experiment design and procedures. This document concludes with an appendix that provides background information concerning the Reduced Gravity Program. Acknowledgments
Hecht, Sharon↗
Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss
Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.
LeBlanc, Adrian↗
Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss
The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged ~ 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space flight and two dosing regimens: 1) an oral dose of 70 mg of alendronate taken weekly during flight or 2) a single intravenous (IV) dose of 4 mg of zoledronic acid given several weeks before flight. Currently the study is focusing on the oral option because of NASA s safety concerns with the IV-administered drug. The protocol requests 10 male or female crewmembers on ISS flights of 90 days or longer. Controls are 16 previous ISS crewmembers with QCT scans of the hip performed by these same investigators. The primary outcome measure for this study is hip trabecular bone mineral density measured by QCT, but other measures of bone mass are performed including peripheral QCT (pQCT) and dual-energy x-ray absorptiometry. Serum and urinary bone markers and renal stone risk measured before, during, and after flight are included. Postflight data are currently being collected from 2 ISS crewmembers. Two additional crewmembers will return this spring after ~6-month missions. To date no untoward effects have been encountered.
Spector, Elisabeth↗
Regional changes in muscle mass following 17 weeks of bed rest
This work reports on the muscle loss and recovery after 17 wk of continuous bed rest and 8 wk of reambulation in eight normal male volunteers. Muscle changes were assessed by urinary levels of 3-methylhistidine (3-MeH), nitrogen balance, dual-photon absorptiometry (DPA), magnetic resonance imaging (MRI), and isokinetic muscle performance. The total body lean tissue loss during bed rest calculated from nitrogen balance was 3.9 +/- 2.1 kg. Although the total loss is minimal, DPA scans showed that nearly all of the lean tissue loss occurred in the lower limbs. Similarly, MRI muscle volume measurements showed greater percent loss in the limbs relative to the back muscles. MRI, DPA, and nitrogen balance suggest that muscle atrophy continued throughout bed rest with rapid recovery after reambulaton. Isokinetic muscle strength decreased significantly in the thigh and calf with no loss in the arms and with rapid recovery during reambulation.
Leblanc, Adrian D.↗
Shuttle-food consumption, body composition and body weight in women
An experiment is conducted to determine whether the NASA Space Shuttle food system can provide the food and fluid required to mitigate weight loss and physical decomposition in 12 female subjects for 28 days. Subjects receive only foods from the Space Shuttle system for four weeks within an 11-wk monitoring period. Dual-energy X-ray absorptiometry is employed throughout the trial period to study lean body mass, percent body fat, and energy-intake levels with attention given to differences the experimental diet and the subjects' typical diet. Percent body fat is found to change significantly with losses of less than 0.05 percent, whereas energy intake based on autonomous diet choices by the participants does not vary significantly. Lean body mass remains unchanged throughout the study in which the subjects receive a relatively low-fat and low-protein menu. The 100 items on the space shuttle list of approved food items are shown to provide a palatable dietary framework for maintaining the health of female astronauts.
Lane, Helen W.↗