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All sourcesNASA NTRSDOE OSTI
NASA NTRS2011

Bone Density Following Three Years of Recovery from Long-Duration Space Flight

It is well recognized that bone mineral density [BMD] at load-bearing sites of the hip and spine sustain significant loss during space flight, estimated at approximately 0.5-1.0% per month. However, the long-term effects on bone health following return from long-duration space flight remain unclear. It is unknown whether BMD for men recovers beyond 1 year following return from space to what would be predicted or if deficits persist. Using our previously created prediction models, we compared the observed BMD of male US crew following 3 years since returning from longduration space flight with what would be predicted if they had not been exposed to microgravity.

Amin, Shreyasee↗
NASA NTRS2011

Space: The Final Frontier of Bone Density

It is a medical requirement at NASA to evaluate the skeletal integrity of "long-duration" astronauts by measuring bone mineral density [BMD] with DXA technology. A long-duration mission is a spaceflight that is greater than 30 days but is typically the continuous 120-180 day missions aboard the International Space Station [ISS]. Not only does NASA use the BMD index to monitor fracture risk in this astronaut population, but these measures are also used to describe the effects of spaceflight, to certify skeletal health readiness for flight, to monitor the recovery of lost bone mass after return to earth, and to evaluate the efficacy of countermeasures to bone loss. However, despite the fact that DXA-based BMD is a widely-applied surrogate for bone strength that is grounded in an abundance of population-based fracture data, its applicability to the long-duration astronaut is limited. The cohort of long-duration astronauts is not the typical group for evaluating osteoporosis or determining age-related fracture risk. The cohort is young (< 55 years), predominantly male and exposed to novel risk factors for bone loss besides the weightlessness of space. NASA is concerned about early onset osteoporosis in the astronaut exposed to long-duration spaceflight, especially since any detectable symptoms are likely to manifest after return to earth and perhaps years after space travel. This risk raises the question: is NASA doing enough now to mitigate a fracture event that may manifest later? This presentation will discuss the limitations and constraints to understanding skeletal changes due to prolonged spaceflight and the recommendations, by clinical experts in osteoporosis and BMD, to transition research technologies for clinical decision-making by NASA.

Sibonga, Jean D.↗
NASA NTRSDate not supplied

Printed Electrochemical Sensor for Quantifying Bone Density Loss in Microgravity

Printed electrochemical biosensors have been developed for astronaut point-of-care testing. Our fabrication approach is complimentary with in-space manufacturing for an on-demand and hands-free fabrication process. These sensors are developed using a combination of thin film materials printing and 3D printing and are comprised of carbon nanotube, gold nanoparticle, silver nanoparticle and dielectric inks to make traditional electrochemical sensor devices. Initial prototyped printed electrochemical sensors demonstrate good electrochemical performance while also displaying low batch to batch variability. Here we report the development of a printed sensor to monitor bone turnover. The absence of load bearing forces experienced in microgravity causes a reduction of overall bone mass and results in the development of space osteopenia/osteoporosis.(1,2) Our approach to identify space osteopenia/osteoporosis is to monitor the change in bone mass indirectly through an excreted biomarker of bone remodeling, amino-terminal collagen crosslinks (NTX). Antibodies specific to NTX are added to the sensor’s electrode ink and applied during the manufacturing process. NTX is measured from a urine sample by changes in voltammetry and electrochemical impedance as it binds to the antibody modified electrode surface. The measurement is rapid, quantitative and requires only small handheld electronics to perform the measurement. By this process, ground and flight physicians will receive frequent and real-time insight into the development of space osteopenia/osteoporosis to guide appropriate countermeasures. REFERENCES [1] Nabavi, N. et al (2011) Bone 49, 965-974. [2] Tamma, R. et al (2009) FASEB J 23, 2549-2554.

in-space manufacturing↗
NASA NTRS2010

Bone Density Following Three Years of Recovery from Long-Duration Space-Flight

Bone loss during long-duration space flight is well recognized, but the long-term implications on bone health following return from flight remain unclear. Among US crew who were involved in long-duration missions in space (Mir and ISS), we have previously shown that at approximately 12 months following return, men, but not women, had BMD values at most sites that were still lower than would be expected had they not been exposed to a prolonged period of microgravity. We now extend our observations to 3 years of follow-up post-flight. Using their age, pre-flight BMD and follow-up time, post-flight BMD values for each US crew were predicted based on the model developed from the community sample. We found BMD measures to be either stable or improve by 3 years relative to their immediate post-flight BMD, however only total hip BMD still remains significantly lower than would be expected had they not been exposed to microgravity. Among male US crew, who have had their BMD measured following at least 3 years of recovery post long-duration flight, they continue to have lower BMD at the hip than would be expected, raising potential concerns regarding future hip fracture risk.

Amin, S.↗
NASA NTRS1999

Bone Density and High Salt Diets in a Space Flight Model

High salt diets accelerate bone loss with aging in patients with postmenopausal osteoporosis except when calcium supplementation is provided. We have observed that the decrease in mineral content of growing femurs in juvenile rats, exposed to a space flight model which unloads the hind limbs , is substantially less in animals fed excess salt. To determine whether excess dietary salt has the same effect on the skeleton of the mature animal whose response to unloading is increased resorption and bone loss rather than impaired growth, we carried out a metabolic study in mature rats with hindlimbs unloaded by tailsuspension.

Arnaud, S. B.↗
NASA NTRS2009

Seeking: Accurate Measurement Techniques for Deep-Bone Density and Structure

We are seeking a clinically-useful technology with enough sensitivity to assess the microstructure of "spongy" bone that is found in the marrow cavities of whole bones. However, this technology must be for skeletal sites surrounded by layers of soft tissues, such as the spine and the hip. Soft tissue interferes with conventional imaging and using a more accessible area -- for example, the wrist or the ankle of limbs-- as a proxy for the less accessible skeletal regions, will not be accurate. A non-radioactive technology is strongly preferred.

Sibonga, Jean↗
NASA NTRS2014

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS mission, DXA BMD and TBS are detecting different effects of ARED exercise and of ARED + Bisphosphonate on the lumbar spine of astronauts. There is emerging evidence associating reduced TBS with terrestrial metabolic bone disorders where a TBS <1.200 is associated with "degraded" while > 1.350 is associated with "normal." However, it is not possible to conclude how the spaceflight-induced changes in TBS increase risk for vertebral fractures in the astronaut or if changes in body composition of the trunk region could be an indirect method of assessing exercise effect on bone microarchitecture. More importantly, this pilot analysis demonstrates a new, minimal risk approach for monitoring changes to vertebral bone microarchitecture. This method could help assess the combined skeletal effects of spaceflight with the effects of aging in the astronaut after return to Earth.

Sibonga, J. D.↗
NASA NTRS1983

Space Station and the life sciences

Previous fundamental research in space life sciences is examined, and consideration is devoted to studies relevant to Space Station activities. Microgravity causes weight loss, hemoconcentration, and orthostatic intolerance when astronauts returns to earth. Losses in bone density, bone calcium, and muscle nitrogen have also been observed, together with cardiovascular deconditioning, fluid-electrolyte metabolism alteration, and space sickness. Experiments have been performed with plants, bacteria, fungi, protozoa, tissue cultures, invertebrate species, and with nonhuman vertebrates, showing little effect on simple cell functions. The Spacelab first flight will feature seven life science experiments and the second flight, two. Further studies will be performed on later flights. Continued life science studies to optimize human performance in space are necessary for the efficient operation of a Space Station and the assembly of large space structures, particularly in interaction with automated machinery.

White, R. J.↗
NASA NTRS1992

Age-related decrements in bone mineral density in women over 65

Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population-based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.

NASA Discipline Musculoskeletal↗
NASA NTRS2003

Non-Invasive Investigation of Bone Adaptation in Humans to Cumulative Daily Mechanical Loading

The goal of our research is to better understand the functional relationship between cumulative daily skeletal loading generated by daily activity and the regulation of bone density and bone structure. We have proposed the calcaneus and tibia as useful model bone sites loaded by internal forces in equilibrium with the ground reaction force during gait. The daily history of the ground reaction force is a good relative measure of daily lower limb and calcaneal loading that can be compared to bone density and structure of the calcaneus and cross-sectional geometry of the tibia and fibula. Over the past several years, we have developed image-processing technologies to improve our ability to measure bone density and structure in the calcaneus and lower leg non-invasively with computed tomography and bone densitometry, or DXA. The objective of our current research effort is to determine the accuracy and precision of our CT and DXA image processing methods.

Whalen, Robert↗
NASA NTRS2013

Combined Effects of Spaceflight and Age in Astronauts as Assessed by Areal Bone Mineral Density [BMD] and Trabecular Bone Score

Spaceflight is a potential risk factor for secondary osteoporosis in astronauts. Although lumbar spine (LS) BMD declines rapidly, more than expected for age, there have been no fragility fractures in astronauts that can clearly be attributed to spaceflight. Recently, astronauts have been returning from 6‐month spaceflights with absolute BMD still above young adult mean BMD. In spite of these BMD measurements, we project that the rapid loss in bone mass over long‐duration spaceflight affects the bone microarchitecture of the LS which might predispose astronauts to premature vertebral fractures. Thus, we evaluated TBS, a novel texture index correlated with vertebral bone microarchitecture, as a means of monitoring changes to bone microarchitecture in astronauts as they age. We previously reported that TBS detects an effect of spaceflight (~6‐month duration), independent of BMD, in 51 astronauts (47+/‐4 y) (Smith et al, J Clin Densitometry 2014). Hence, TBS was evaluated in serial DXA scans (Hologic Discovery W) conducted triennially in all active and retired astronauts and more frequently (before spaceflight, after spaceflight and until recovery) in the subset of astronauts flying 4‐6‐ month missions. We used non‐linear models to describe trends in observations (BMD or TBS) plotted as a function of astronaut age. We fitted 1175 observations of 311 astronauts, pre‐flight and then postflight starting 3 years after landing or after astronaut's BMD for LS was restored to within 2% of preflight BMD. Observations were then grouped and defined as follows: 1) LD: after exposure to at least one long‐duration spaceflight > 100 days and 2) SD: before LD and after exposure to at least one short-duration spaceflight < 30 days. Data from males and females were analyzed separately. Models of SD observations revealed that TBS and BMD had similar curvilinear declines with age for both male and female astronauts. However, models of LD observations showed TBS declining with age while BMD appeared stable or trending upward. For females (n=8) LD observations were too few to discern a trend. Notably, models describing trends in TBS appeared to be more sensitive to the effects of age than the models for BMD. We conclude that TBS may provide an additional index for the lumbar spine to monitor the combined changes due to spaceflight and due to aging. This increased knowledge may enhance the ability to identify an intervention trigger for premature vertebral fractures in astronauts.

Sibonga, Jean D.↗
NASA NTRS2017

Mapping Bone Mineral Density Obtained by Quantitative Computed Tomography to Bone Volume Fraction

Methods for relating or mapping estimates of volumetric Bone Mineral Density (vBMD) obtained by Quantitative Computed Tomography to Bone Volume Fraction (BVF) are outlined mathematically. The methods are based on definitions of bone properties, cited experimental studies and regression relations derived from them for trabecular bone in the proximal femur. Using an experimental range of values in the intertrochanteric region obtained from male and female human subjects, age 18 to 49, the BVF values calculated from four different methods were compared to the experimental average and numerical range. The BVF values computed from the conversion method used data from two sources. One source provided pre bed rest vBMD values in the intertrochanteric region from 24 bed rest subject who participated in a 70 day study. Another source contained preflight vBMD values from 18 astronauts who spent 4 to 6 months on the ISS. To aid the use of a mapping from BMD to BVF, the discussion includes how to formulate them for purpose of computational modeling. An application of the conversions would be used to aid in modeling of time varying changes in vBMD as it relates to changes in BVF via bone remodeling and/or modeling.

Pennline, James A.↗