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Shackelford, L.

Publications and source records attributed to Shackelford, L..

8 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Update of Bisphosphonate Flight Experiment

Elevated bone resorption is a hallmark of human spaceflight and bed rest indicating that elevated remodeling is a major factor in the etiology of space flight bone loss. In a collaborative effort between the NASA and JAXA space agencies, we are testing whether an antiresorptive drug would provide additional benefit to in-flight exercise to ameliorate bone loss and hypercalciuria during long-duration spaceflight. Measurements of bone loss include DXA, QCT, pQCT, urinary and blood biomarkers. We have completed analysis of R+1year data from 7 crewmembers treated with alendronate during flight, as well as immediate post flight (R+<2wks) data from 6 of 10 concurrent controls without treatment. The treated astronauts used the Advanced Resistive Exercise Device (ARED) during their missions. The purpose of this report is twofold: 1) to report the results of inflight, post flight and one year post flight bone measures compared with available controls with and without the use of ARED; and 2) to discuss preliminary data on concurrent controls. The figure below compares the BMD changes in ISS crewmembers exercising with and without the current ARED protocol and the alendronate treated crewmembers also using the ARED. This shows that the use of ARED prevents about half the bone loss seen in early ISS crewmembers and that the addition of an antiresorptive provides additional benefit. Resorption markers and urinary Ca excretion are not impacted by exercise alone but are significantly reduced with antiresorptive treatment. Bone measures for treated subjects, 1 year after return from space remain at or near baseline. DXA data for the 6 concurrent controls using the ARED device are similar to DXA data shown in the figure below. QCT data for these six indicate that the integral data are consistent with the DXA data, i.e., comparing the two control groups suggests significant but incomplete improvement in maintaining BMD using the ARED protocol. Biochemical data of the concurrent control group await sample return and analysis. The preliminary conclusion is that an antiresorptive may be an effective adjunct to exercise during long-duration spaceflight.

LeBlanc, A.↗
NASA NTRS2011

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

This poster reviews the possibility of using Bisphosphonates to counter the bone loss that is experienced during space flight. The Hypothesis that is tested in this experiment is that the combined effect of anti-resorptive drugs plus in-flight exercise regimen will attenuate space flight induced loss in bone mass and strength and reduce renal stone risk. The experiment design, the status and the results are described.

LeBlanc, A.↗
NASA NTRS2009

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↗
NASA NTRS2009

Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

Smith, Scott M.↗
NASA NTRS1999

T2 vertebral bone marrow changes after space flight

Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

NASA Experiment Number 284054↗
NASA NTRS1998

Future human bone research in space

Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

NASA Center JSC↗
NASA NTRS1995

Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software

This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.

NASA Discipline Musculoskeletal↗