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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

Sibonga, Jean D.↗
NASA NTRS2001

Animal models for osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

NASA Discipline Regulatory Physiology↗
NASA NTRS1987

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Schneider, Victor S.↗
NASA NTRS1995

Pathophysiology of immobilization osteoporosis

The reduction of gravity-related forces on the skeleton creates a type of osteoporosis that is unique because its severity is dependent on the mechanical stress bearing function of the skeleton as well as the length of time that the forces are absent or reduced. Bones that bear weight under normal conditions are more affected than bones that normally do not bear weight. The cytokine environment and the cells in the affected bones are altered in time so that stem cells produce fewer new cells and the differentiated cells tend to be less active. These alterations in the local environment of the affected parts appear to resemble those of age- and disease-associated systemic forms of osteoporosis. The osteoporosis produced as a result of the loss of normal activity however, appears to be at least partially reversible through remobilization, strenuous exercise, and--possibly in the future--cytokine therapy.

Non-NASA Center↗
NASA NTRS2017

Risk Of Early Onset Osteoporosis Due To Spaceflight

Bone minerals decline in microgravity, and bone mineral density (BMD) losses of approximately -1 to -1.5% per month were calculated for astronauts serving on long-duration missions prior to 2009. It is unclear whether BMD losses will stabilize with time in space, or continue to diminish with time. In addition, it is unknown if fractional gravity, present on the moon and Mars, will mitigate the mineral loss. Clinicians diagnose osteoporosis in premenopausal females and males younger than 50 years on the basis of BMD T-scores < -2.5 (hip and lumbar spine) accompanied by clinical evidence of a fragility fracture. If mission-related changes to the skeleton cannot be corrected by rehabilitation after the mission, crewmembers could be at risk for premature osteoporosis-related fractures in later life. To mitigate this risk it is necessary to understand the dynamics underlying the BMD changes that occur in microgravity, to monitor for the persistence of changes after space flight, and to evaluate if and how current and future osteoporosis treatments might be used to mitigate the risk of long-term skeletal problems in astronauts.

Sibonga, Jean↗
NASA NTRS1991

The Role of Calcium in Osteoporosis

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

Arnaud, C. D.↗
NASA NTRS1990

Prevention of space flight induced soft tissue calcification and disuse osteoporosis

Medical complications such as renal stone formation, increased uric acid output, and disuse osteoporosis are discussed. A series of experiments was conducted in order to study and eventually reduce these flight hazards. Attempts to prevent the negative calcium balance and loss of calcaneal density during prolonged bed rest had only a limited success. Of the five biochemical regiments tested, only diphosphonate applied in a high dose had a positive effect in elliminating mineral losses. It is found that clodronate can prevent disuse osteoporosis and that fluoride can enhance bone formation. It is concluded that exercises, combined with pharmaceutical agents, are beneficial during long-duration space missions.

Schneider, Victor S.↗
NASA NTRS1994

Irreversibility of advanced osteoporosis: Limited role for pharmacologic intervention

Osteoporosis is of medical interest only because it increases bone fragility and risk of fracture, and except for relief of symptoms, preventing fracture is the only purpose of intervention. To prevent the first fracture, adequate bone density must be accumulated and conserved, but to prevent subsequent fracture, bone density must be augmented so that the supportive function of the skeleton can be restored. Almost 50 years after the recognition of post menopausal osteoporosis as a clinical entity, not one of the many treatments that have been used has been demonstrated to be efficacious in reducing subsequent fracture risk. My purpose is not to recite this chronicle of disappointment, but to account for it in terms of bone biology, to consider some possible exceptions, and to reiterate the importance of preventing damage to the skeleton rather than belatedly attempting its repair.

Parfitt, A. M.↗
NASA NTRS2002

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

NASA Discipline Regulatory Physiology↗
DOE OSTI2021

HA15 alleviates bone loss in ovariectomy-induced osteoporosis by targeting HSPA5

The imbalance between osteogenesis and adipogenesis in the bone marrow is the main characteristic of osteoporosis (OP). Thus, exploring regulation of the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts and adipocytes is important to identify novel targets for the treatment of OP. In the present study, the master regulator of endoplasmic reticulum (ER) stress, heat shock protein family A (Hsp70) member 5 (HSPA5) was shown to significantly accumulate in osteoblasts and adipocytes, but not in osteoclasts in bone sections from aged and postmenopausal OP mice. In vitro study revealed that HSPA5 negatively modulated osteogenic differentiation and positively promoted adipogenic differentiation, and that targeting HSPA5 with its inhibitor HA15 enhanced osteogenic differentiation and inhibited adipogenic differentiation. Also, HA15 treatment induces ER stress and autophagy, and decreases apoptosis in cells. We constructed a postmenopausal OP model in mice with ovariectomy surgery, and treated the mice with HA15. The results showed that HA15 treatment induced appropriate ER stress, activated autophagy and decreased apoptosis in osteoblasts, thereby alleviating bone loss in vivo. Our results indicated that HSPA5 participated in OP pathogenesis by regulating the differentiation of BMSCs. HSPA5 may serve as a new target for the treatment of OP, and targeting HSPA5 with HA15 prevents the progression of OP and provides a candidate therapeutic molecule for postmenopausal OP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Osteoporosis Treatments Affect Bone Matrix Maturation in a Rat Model of Induced Cortical Remodeling

ABSTRACT To test how osteoporosis drugs affect bone matrix maturation during cortical bone remodeling, 72 pregnant rats were switched from a 0.4% to a 0.01% calcium diet at parturition for a 23‐day lactation period. At weaning, eight dams were sacrificed to establish baseline values, while the remaining dams were returned to 0.4% calcium and treated with vehicle (saline), sodium fluoride (NaF), zoledronic acid (ZA), or sclerostin antibody (Scl‐Ab) for either 7 or 28 days (eight animals per group per time point). Femora were examined by μCT, dynamic histomorphometry, Fourier transform infrared imaging, and three‐point bending of notched specimens. Cortical porosity decreased in all groups from baseline to day 28. Intracortical mineralizing surface (MS/BS) and mineral apposition rate (MAR), as well as the mineral‐to‐matrix ratio were unaffected by treatment, but intracortical crystallinity was increased in the ZA group at day 10 compared with vehicle. Cortical area increased in all groups over 28 days mainly because of an addition of bone at the endocortical surface. Endocortical MS/BS did not vary among the groups, but endocortical MAR was suppressed in the NaF group at day 2 and elevated in the Scl‐Ab group at day 4 compared with vehicle. Endocortical mineral‐to‐matrix ratio was increased at days 5 and 10 following NaF treatment and endocortical crystallinity was increased at day 5 following ZA treatment compared with vehicle. Fracture toughness did not differ among the groups. Thus, the treatments affected matrix maturation more strongly at the endocortical then intracortical envelope. In this model of induced remodeling, the bone formation phase is synchronized at multiple sites, facilitating study of the effects of drugs or other bone‐targeting agents on matrix maturation independent of their effects on the initiation of remodeling. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1983

Tibial changes in experimental disuse osteoporosis in the monkey

The mechanical properties and structural changes in the monkey tibia with disuse osteoporosis and during subsequent recovery are investigated. Bone mending stiffness is evaluated in relation to microscopic changes in cortical bone and Norland bone mineral analysis. Restraint in the semireclined position is found to produce regional losses of bone most obviously in the anterior-proximal tibiae. After six months of restraint, the greatest losses of bone mineral in the proximal tibiae range from 23 percent to 31 percent; the largest changes in bone stiffness range from 36 percent to 40 percent. Approximately eight and one-half months of recovery are required to restore the normal bending properties. Even after 15 months of recovery, however, the bone mineral content does not necessarily return to normal levels. Histologically, resorption cavities in cortical bone are seen within one month of restraint; by two and one-half months of restraint there are large resorption cavities subperiosteally, endosteally, and intracortically. After 15 months of recovery, the cortex consists mainly of first-generation haversian systems. After 40 months, the cortex appears normal, with numerous secondary and tertiary generations of haversian systems.

Young, D. R.↗
NASA NTRS1994

Exercise and osteoporosis: Methodological and practical considerations

Physical activity may have important implications for enhancing bone density prior to the initiation of space flight, for preserving bone density during zero gravity, and for rehabilitating the skeleton upon return to Earth. Nevertheless, the beneficial effects of exercise upon the skeleton have not been proven by controlled trials and no consensus exists regarding the type, duration, and intensity of exercise necessary to make significant alterations to the skeleton. The following sections review our current understanding of exercise and osteoporosis, examine some of the methodological shortcomings of these investigations, and make research recommendations for future clinical trials.

Block, Jon E.↗
NASA NTRS1976

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Cann, Christopher↗
NASA NTRS1999

Mechanical signaling in the development of postmenopausal osteoporosis

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Non-NASA Center↗
NASA NTRS1981

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Young, D. R.↗