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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1986

Immobilization-associated osteoporosis in primates

Osteopenic changes in the tibial compact bone of fifteen adult male monkeys immobilized for up to 7 months are examined histologically. Osteonal formation in the proximal tibia is analyzed. The analysis reveals the loss of haversian bone in the proximal tibia, increased activation with excessive depth of penetration of osteoclastic activity, rapid bone loss, and resorption cavities of irregular size and orientation. Osteonal formation following reambulation is examined; the recovery of cortical is a repair and rejuvenation process characterized by refilling of resorption cavities and remodeling activities.

Young, D. R.↗
NASA NTRS1989

Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity

During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

Nechay, Bohdan R.↗
NASA NTRS1999

Expression of Novel Gene Products Upregulated by Disuse is Normalized by an Osteogenic Mechanical Stimulus: Evidence for the Molecular Basis of a Low Level Biomechanical Countermeasure for Osteoporosis?

The National Research Council's report entitled: A Strategy for Space Biology and Medical Science, highlighted several areas of fundamental scientific investigation which must be addressed to make long-term space exploration not only feasible, but safe. This "Goldberg Strategy," as well as several subsequent reports published by the NRC's Space Studies Board (e.g., Assessment of Programs in Space Biology and Medicine, Smith et. al., 1991), suggests that the principal hurdle to man's extended presence in space is the osteopenia which parallels reduced gravity. Ironically, the most significant risk to the skeleton may only be realized on return to normal gravitational fields, and full recovery of bone mass may never occur. Effective counter-measures to this microgravity induced bone loss are thus essential. Considering the similarities of space and aging induced osteopenia, an indisputable benefit of such a prophylaxis would be its potential as a treatment for the bone loss which plagues over 25 million people in the U.S. The osteogenic potential of mechanical strain is strongly frequency dependent, with sensitivity increasing up through at least 60 Hz (cycles per second). One hundred seconds per day of a 1 Hz cyclic loading will inhibit disuse osteopenia only if sufficient in magnitude to engender 1000 microstrain (mu(epsilon)) in the tissue. When loading is applied at 30 Hz, however, mechanical strains on the order of 5O mu(epsilon) (approx. 1% of the peak strains which occur in bone during vigorous functional activity), can stimulate bone formation in a duration dependent manner. In longer term animal studies, strains of less than 10 mu(epsilon), induced non-invasively via a whole body vibration, will stimulate bone formation on the surfaces of trabeculae, increase bone density, and improve strength. Finally, preliminary results from a double blind prospective clinical trial shows promise in inhibiting the bone loss which parallels the menopause. Based on these observations, we propose that these high frequency, low magnitude, mechanical strains effectively serve as a "surrogate" for musculoskeletal ground reaction forces, and thus represent an ideal countermeasure to the osteopenia which parallels microgravity conditions. The specific goal of this NASA funded work is to identify genes in bone upregulated by disuse, and to determine the efficacy of an osteogenic mechanical stimulus to downregulate their expression.

Rubin, C.↗
NASA NTRS1992

Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria

We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Regulatory Physiology↗
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 NTRS2008

Mice Drawer System

The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

Cancedda, Ranieri↗
NASA NTRS1985

Assessment of metabolic bone diseases by quantitative computed tomography

Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

Minerals/analysis↗
NASA NTRS2008

Adaptation of the Skeletal System during Long-duration Spaceflight

This review will highlight evidence from crew members flown on space missions greater than 90 days to suggest that the adaptations of the skeletal system to mechanical unloading may predispose crew members to an accelerated onset of osteoporosis after return to Earth. By definition, osteoporosis is a skeletal disorder - characterized by low bone mineral density and structural deterioration - that reduces the ability of bones to resist fracture under the loading of normal daily activities. Involutional or agerelated osteoporosis is readily recognized as a syndrome afflicting the elderly population because of the insipid and asymptomatic nature of bone loss that does not typically manifest as fractures until after age approximately 60. It is not the thesis of this review to suggest that spaceflight-induced bone loss is similar to bone loss induced by metabolic bone disease; rather this review draws parallels between the rapid and earlier loss in females that occurs with menopause and the rapid bone loss in middle-aged crew members that occurs with spaceflight unloading and how the cumulative effects of spaceflight and ageing could be detrimental, particularly if skeletal effects are totally or partially irreversible. In brief, this report will provide detailed evidence that long-duration crew members, exposed to the weightlessness of space for the typical long-duration (4-6 months) mission on Mir or the International Space Station -- 1. Display bone resorption that is aggressive, that targets normally weight-bearing skeletal sites, that is uncoupled to bone formation and that results in areal BMD deficits that can range between 6-20% of preflight BMD; 2. Display compartment-specific declines in volumetric BMD in the proximal femur (a skeletal site of clinical interest) that significantly reduces its compressive and bending strength and which may account for the loss in hip bone strength (i.e., force to failure); 3. Recover BMD over a post-flight time period that exceeds spaceflight exposure but for which the restoration of whole bone strength remains an open issue and may involve structural alteration; and 4. Display risk factors for bone loss -- such as the negative calcium balance and down-regulated calcium-regulating hormones in response to bone atrophy -- that can be compounded by the constraints of conducting mission operations (inability to provide essential nutrients and vitamins). The full characterization of the skeletal response to mechanical unloading in space is not complete. In particular, countermeasures used to date have been inadequate and it is not yet known whether more appropriate countermeasures can prevent the changes in bone that have been found in previous flights, knowledge gaps related to the effects of prolonged (greater than or equal to 6 months) space exposure and to partial gravity environments are substantial, and longitudinal measurements on crew members after spaceflight are required to assess the full impact on skeletal recovery.

Sibonga, Jean D.↗
NASA NTRS2000

Bone Quest - A Space-Based Science and Health Education Unit

This proposal addresses the need for effective and innovative science and health education materials that focus on space bone biology and its implications for bone health on Earth. The focus of these materials, bone biology and health, will increase science knowledge as well as health awareness. Current investigations of the bone loss observed after long-duration space missions provide a link between studies of bone health in space, and studies of osteoporosis, a disease characterized by bone loss and progressive skeletal weakness. The overall goal of this project is to design and develop web-based and print-based materials for high school science students, that will address the following: a) knowledge of normal bone biology and bone biology in a microgravity environment; b) knowledge of osteoporosis; c) knowledge of treatment modalities for space- and Earth-based bone loss; and d} bone-related nutrition knowledge and behavior. To this end, we propose to design and develop a Bone Biology Tutorial which will instruct students about normal bone biology, bone biology in a microgravity environment, osteoporosis - its definition, detection, risk factors, and prevention, treatment modalities for space- and Earth-based bone loss, and the importance of nutrition in bone health. Particular emphasis will be placed on current trends in . adolescent nutrition, and their relationships to bone health. Additionally, we propose to design and develop two interactive nutrition/health ' education activities that will allow students to apply the information provided in the Bone Biology Tutorial. In the first, students will apply constructs provided in the Bone Biology Tutorial to design "Bone Health Plans" for space travelers.

Smith, Scott M.↗
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.↗
DOE OSTI2021

Glucocorticoids suppressed osteoblast differentiation by decreasing Sema3A expression via the PIK3/Akt pathway

Highlights: • Dex decreased Sema3A expression by suppressing the PI3K/Akt pathway. • Sema3A reversed Dex-induced suppression of osteoblast differentiation. • Sema3A reversed the Dex-mediated reduced transcriptional activity of β-catenin. Glucocorticoids(GCs) are extensively used to treat inflammatory and autoimmune diseases. Excessive prolonged exposure to glucocorticoids is associated with an increased risk of osteoporosis. The inhibition of osteoblast differentiation by GCs is suggested as a major cause for GCs-induced osteoporosis (GIO). However, the precise mechanism underlying the role of GCs in osteoblasts differentiation is not fully elucidated. Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, enhances bone formation and promotes fracture healing, which is known to increase osteoblastic differentiation and stimulate osteogenesis in bone metabolism. Here, the present study explored the effect of Sema3A in osteoblast differentiation using dexamethasone (Dex) treatment of bone marrow stromal cells (BMSCs). Dex treatment decreased Sema3A expression in BMSCs in a dose-dependent manner. Moreover, Dex stimulation suppressed the differentiation of osteoblasts by reducing alkaline phosphatase (ALP) activity, osteoblastic marker genes expression and mineralization, but all of these effects were ameliorated by exogenous recombinant Sema3A administration. Furthermore, exogenous Sema3A administration reversed the Dex-mediated decrease in nuclear accumulation of β-catenin and β-catenin activity in BMSCs. Meanwhile, Dex was capable of simultaneously suppressing the phosphorylation of protein kinase B(Akt) and the expression level of Sema3A in BMSCs. These changes were significantly abolished by the PI3K/Akt agonist. These results suggest that Dex inhibits osteoblast differentiation by suppressing Sema3A expression via the PI3K/Akt pathway. These data provide new insights into the molecular mechanisms of Dex-induced osteoblast differentiation inhibition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

LOXG473A induces the formation of osteoclasts in RAW264.7 cells via IL-6/JAK2/STAT3 signaling

Formation of osteoclasts is known to be closely associated with osteoporosis progression. LOX is a key enzyme that catalyzes the synthesis of collagen, which is the new mediator in osteoclast formation. However, the effect of LOXG473A on of osteoclast formation needs to be explored. Thereby, we sought to explore the effect of LOX{sub G473A} on formation of osteoclasts and its underlying mechanism. To investigate the function of LOX{sub G473A} in osteoclast formation, Raw264.7 cells were stably transfected with LOX-WT or LOX-MUT (LOX{sub G473A}). Real-time PCR and western blotting were used to detect the relative levels of osteoclast formation related genes and proteins. TRAP staining and immunofluorescence staining were used to test the ability of Raw264.7 cells to form osteoclasts and the ability of cells to form rings, respectively. Bone erosion assay was used to test bone resorptive activity. The data indicated that LOX{sub G473A} significantly enhanced the ability of osteoclasts forming, ring-forming and bone resorpting in Raw264.7 cells. Mechanically, LOX{sub G473A} upregulated the expressions of NFATC1, ACP5, CTSK, IL-6, and the proportion of p-JAK2/JAK2 and p-STAT3/STAT3, thereby promoting the formation of osteoclasts. In conclusion, we have verified that LOX{sub G473A} induces the proliferation of osteoclasts in Raw264.7 cells via IL-6/JAK2/STAT3 signaling, suggesting a novel strategy for studying osteoporosis.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2024

Risk of Bone Fracture due to Spaceflight-induced Changes to Bone

The Human Research Program (HRP) is taking a biomechanical approach to assessing subsequent fracture risk in active astronauts as a consequence of spaceflight exposure. Triennial testing of active and retired astronauts continues as Space Medicine monitors for a premature diagnosis of primary osteoporosis, which is associated with age-related bone loss and skeletal fragility. This updated 2023 Fracture Evidence Report has expanded the description of skeletal changes to capture the full effects of spaceflight on bone: • Recent analysis of fractures from health records of the full astronaut cohort, suggests an increased incidence rate of hip and spine fractures in astronauts following longer spaceflight duration flights compared to incident rates found in shorter duration flights. • Routine preflight-to-postflight surveillance by DXA (dual-energy x-ray absorptiometry) does not provide the full detection of loss and recovery in the long-duration (LD) astronaut nor the full recovery of hip trabecular bone. • The inclusion of hip quantitative computed tomography (QCT) in flight studies delineates effects of spaceflight, of countermeasures, and of post-flight recovery on cortical and trabecular bone parameters—some of which are verified predictors of hip fracture in the aged. • QCT detects and compares the distinct countermeasure effects of the pharmaceutical alendronate and of resistive exercise (on the Advanced Resistive Exercise Device, ARED) in specific cortical and trabecular bone sub-regions during spaceflight. • A published comparison of QCT-determined loss rates of hip trabecular bone in LD astronauts compared to terrestrial cohorts suggest that accelerated loss rates in trabecular volumetric BMD (vBMD) during spaceflight might be analogous to skeletal effects of accelerated loss rates in females due to menopause, potentially leading to disruptions in trabecular microarchitecture. • A dataset of finite element (FE) estimates of hip bone strength in aging terrestrial cohorts (spanning astronaut age-range) provides comparative context for changes in the FE of hip bone strength in LD astronauts, including comparison (force unit of newton) to percentiles (50th, 75th, and 100th) of sex-matched aged humans with hip fractures. • Risk of fracture, due to the mechanical overloading of bones, is being updated with IMPACT, the next-generation tool suite for probabilistic risk assessment (PRA) for exploration missions being created by the Exploration and Medical Capability Element (ExMC) at NASA. IMPACT is currently in development and will not be included in this 2024 update. The risk for fracture necessitates understanding the relationship between applied loads to bone and the biomechanical competence of bone. The Risk for Early Onset Osteoporosis focuses on the weakened condition of bone (including development of new technologies, measurements of novel skeletal attributes, translation of multiple measures to an index of bone fragility, and interpretations of data used to reflect a weakened bone), while the Risk for Fracture assesses factors that influence the probability an astronaut would encounter applied loads exceeding the biomechanical competence of bones, resulting in fracture. This Evidence Report combines the research gaps and tasks associated with both risks.

Fracture↗
NASA NTRS1978

A brief review of space flight calcium metabolism: Results and methodologies

Space flight induced osteoporosis was described. The techniques that were used to measure and detect the osteoporosis were also described. Areas of calcium metabolism were shown to be very important in the investigation into more sensitive detection and measurement techniques of bone demineralization.

Source record↗