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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

Sibonga, Jean↗
NASA NTRS1998

Role of Corticosteroids in Bone Loss During Space Flight

The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

Wronski, Thomas J.↗
NASA NTRS2010

Epidemiologic Analyses of Risk Factors for Bone Loss and Recovery Related to Long-Duration Space Flight

AIM 1: To investigate the risk of microgravity exposure on long-term changes in bone health and fracture risk. compare data from crew members ("observed") with what would be "expected" from Rochester Bone Health Study. AIM 2: To provide a summary of current evidence available on potential risk factors for bone loss, recovery & fracture following long-duration space flight. integrative review of all data pre, in-, and post-flight across disciplines (cardiovascular, nutrition, muscle, etc.) and their relation to bone loss and recovery

Sibonga, Jean↗
NASA NTRS1994

Prevent and cure disuse bone loss

Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

Jee, Webster S. S.↗
NASA NTRS2009

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↗
NASA NTRS1998

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

NASA Discipline Musculoskeletal↗
NASA NTRS1999

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and Their Implications for Bone Strain

The human zero-gravity locomotion simulator and the cadaver simulator offer a powerful combination for the study of the implications of exercise for maintaining bone quality during space flight. Such studies, when compared with controlled in-flight exercise programs, could help in the identification of a strain threshold for the prevention of bone loss during space flight.

Peterman, M.↗
NASA NTRS2016

Acute Effects of Simulated Space Radiation and Micro-Gravity on Cancellous Bone Loss in Mice Tibiae

Space radiation and micro-gravity are the two major obstacles impeding human exploration of Mars and beyond. Long-duration space flights expose astronauts to high doses of high linear energy transfer (LET) radiation as well as prolonged periods of skeletal disuse due to weightlessness. One important consequence of both radiation exposure and micro-gravity is acute bone loss. However, biological responses to different radiation types and combined radiation and micro-gravity environments remain unknown. Thus, the purpose of this study is to compare the acute effects of different radiation species and simulated weightlessness on bone degeneration for the purpose of developing accurate risk assessments of prolonged space flight. Mouse models were used to simulate space flight-relevant doses of different radiation types as well as weightlessness via hind-limb unloading. Three groups of mice (n 9) were irradiated with 1 Gy (Gray) H+, 1 Gy 56Fe, and 1 Gy combined H+ and 56Fe (dual ion) respectively and compared to sham irradiated (n 9) and 2 Gy 56Fe irradiated positive controls (n 6). Two groups of mice (n 9) were hind-limb unloaded for three days and then either sham irradiated or dual ion irradiated respectively, followed by subsequent hind-limb unloading for 11 days. Cancellous tissue from tibiae metaphyses were harvested 11 days post-irradiation for ex vivo micro-computed tomography analysis. Microarchitecture parameters including bone volume to total volume ratio (BVTV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.S), and connectivity density (Conn.D) will be quantified using a novel automated segmentation procedure developed in our lab. The anticipated results will be instrumental in developing counter-measures against micro-gravity and radiation-induced bone loss. Moreover, possible synergistic effects may provide insight into underlying mechanisms mediating biological response.

Micro-Gravity↗
NASA NTRS1992

Bone loss and human adaptation to lunar gravity

Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

Keller, T. S.↗
NASA NTRS2015

Dietary Supplement Attenuates Radiation-Induced Osteoclastogenic and Oxidative Stress-Related Responses and Protects Adult Mice from Radiation-Induced Bone Loss

Our central hypothesis is that oxidative stress plays a key role in cell dysfunction and progressive bone loss caused by radiation exposure during spaceflight. In animal studies, excess free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. We previously reported that exposure to low or high-LET radiation rapidly increases expression levels of pro-osteoclastogenic and oxidative stress-related genes in bone and marrow, followed by pathological changes in skeletal structure. To screen various antioxidants for radioprotective effects on bone, 4 month old, male C57Bl6/J mice were treated with a dietary antioxidant cocktail, injectable alpha-lipoic acid, or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs total body radiation and one day later marrow cells were collected and the relevant genes analyzed for expression levels. Of the candidates tested, DP was most effective in reducing bone resorption-related gene expression. Microcomputed tomography revealed that DP also prevented the radiation-induced deterioration of skeletal microarchitecture, as indicated by percent bone volume, trabecular spacing and trabecular number. DP had similar protective effects on skeletal structure after sequential exposure to protons (0.5 Gy, 150MeV/n) and 56Fe 0.5Gy, 600 MeV/n). When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerted pro-osteogenic effects apart from previously identified anti-resorptive actions, which may contribute to radioprotection of skeletal tissue. In conclusion, a diet enriched in certain types of antioxidants and polyphenols such as DP may be useful as an intervention to protect tissues from degenerative effects of ionizing radiation.

Globus, Ruth↗
NASA NTRS1997

Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

We demonstrated for the first time that vitamin D3 influences the effect of PTH on bone cell calcium ion levels. This is a rapid effect, taking place within seconds/minutes. This may prove to be a critical contribution to our understanding of bone physiology in that these two hormones are among the most potent regulators of bone calcium content and of systemic calcium homeostasis. Together with the data gathered from the study of astronauts exposed to microgravity for extended periods, these observations suggest the interaction of vitamin D3 and PTH as a possible therapeutic target in the treatment of bone loss disorders such as osteoporosis and disuse atrophy. Chronic exposure of cultured osteoblasts to vitamin D, altered the number of voltage-sensitive Ca(+2) channels expressed. Estrogen treatment yielded a similar result, suggesting that there is overlap in the mechanism by which these hormones elicit long-term effects on bone cell calcium homeostasis.

Li, Wei↗
NASA NTRS1999

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Halloran, B.↗
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 NTRS2000

Disuse bone loss in hindquarter suspended rats: partial weightbearing, exercise and ibandronate treatment as countermeasures

The purpose of this study was to evaluate potential countermeasures for bone loss during long-term space missions in the hindquarter suspended rat, including partial weight bearing (surrogate for artificial gravity) episodic full weight bearing (2 hour/day full weight bearing) and treatment with the third generation bisphosphonate ibandronate (Roche). Graded mechanical loading was studied by housing the animals on a novel servo controlled force plate system which permitted the titration of mechanical force at varying frequency and amplitude and different levels of weight bearing. The force plate, which forms the cage floor, is a glass platform supported by an 18" diameter speaker cone filled with expanding polyurethane foam. An infrared optical sensor attached to the speaker cone yields a voltage linearly related to vertical displacement of the glass platform. The dynamic force on the paw was computed as a product of the apparent mass of the animal on the platform at rest and the acceleration of the platform determined from the second derivative of the optical sensor output. The mass of the animal on the platform was varied by adjusting tension on the tether suspending the animal. Mechanical impact loading was titrated with the force plate resonating at different frequencies, including 3 Hz and 16 Hz.

Non-NASA Center↗
NASA NTRS1992

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Randomized Controlled Trial↗
NASA NTRS2016

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31% decrease in bone volume ratio, a 14% decrease in trabecular thickness, and a 20% decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1.This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

microgravity↗
NASA NTRS2016

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31 decrease in bone volume ratio, a 14 decrease in trabecular thickness, and a 20 decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1. This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

stem cells↗