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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2002

From Milk to Bones, Moving Calcium Through the Body: Calcium Kinetics During Space Flight

Did you know that when astronauts are in space, their height increases about two inches? This happens because the weightlessness of space allows the spine, usually compressed in Earth's gravity, to expand. While this change is relatively harmless, other more serious things can happen with extended stays in weightlessness, notably bone loss. From previous experiments, scientists have observed that astronauts lose bone mass at a rate of about one percent per month during flight. Scientists know that bone is a dynamic tissue - continually being made and repaired by specialized bone cells throughout life. Certain cells produce new bone, while other cells are responsible for removing and replacing old bone. Research on the mechanisms of bone metabolism and the effects of space flight on its formation and repair are part of the exciting studies that will be performed during STS-107. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. Ninety-nine percent of calcium in the body is stored in the skeleton. However, calcium may be released, or resorbed, from bone to provide for other tissues when you are not eating. To better understand how and why weightlessness induces bone loss, astronauts will participate in a study of calcium kinetics - that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Scott Smith↗
NASA NTRS2007

Artificial Gravity: Effects on Bone Turnover

The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

Heer, M.↗
DOE OSTI2024

Aging impairs the osteocytic regulation of collagen integrity and bone quality

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII ocy–/– ) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRII ocy–/– bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1994

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Review↗
NASA NTRS1996

Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

NASA Discipline Musculoskeletal↗
DOE OSTI2023

Sostdc1 Suppression in the Absence of Sclerostin Potentiates Anabolic Action of Cortical Bone in Mice

ABSTRACT The development of Wnt-based osteoanabolic agents has progressed rapidly in recent years, given the potent effects of Wnt modulation on bone homeostasis. Simultaneous pharmacologic inhibition of the Wnt antagonists sclerostin and Dkk1 can be optimized to create potentiated effects in the cancellous bone compartment. We looked for other candidates that might be co-inhibited along with sclerostin to potentiate the effects in the cortical compartment. Sostdc1 (Wise), like sclerostin and Dkk1, also binds and inhibits Lrp5/6 coreceptors to impair canonical Wnt signaling, but Sostdc1 has greater effects in the cortical bone. To test this concept, we deleted Sostdc1 and Sost from mice and measured the skeletal effects in cortical and cancellous compartments individually. Sost deletion alone produced high bone mass in all compartments, whereas Sostdc1 deletion alone had no measurable effects on either envelope. Mice with codeletion of Sostdc1 and Sost had high bone mass and increased cortical properties (bone mass, formation rates, mechanical properties), but only among males. Combined administration of sclerostin antibody and Sostdc1 antibody in wild-type female mice produced potentiation of cortical bone gain despite no effect of Sostdc1 antibody alone. In conclusion, Sostdc1 inhibition/deletion can work in concert with sclerostin deficiency to improve cortical bone properties. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2003

Disuse exaggerates the detrimental effects of alcohol on cortical bone

BACKGROUND: Alcohol abuse is associated with an increased risk for osteoporosis. However, comorbidity factors may play an important role in the pathogenesis of alcohol-related bone fractures. Suboptimal mechanical loading of the skeleton, an established risk factor for bone loss, may occur in some alcohol abusers due to reduced physical activity, muscle atrophy, or both. The effect of alcohol consumption and reduced physical activity on bone metabolism has not been well studied. The purpose of this study was to determine whether mechanical disuse alters bone metabolism in a rat model for chronic alcohol abuse. METHODS: Alcohol was administered in the diet (35% caloric intake) of 6-month-old male rats for 4 weeks. Rats were hindlimb-unloaded the final 2 weeks of the experiment to prevent dynamic weight bearing. Afterward, cortical bone histomorphometry was evaluated at the tibia-fibula synostosis. RESULTS: At the periosteal surface of the tibial diaphysis, alcohol and hindlimb unloading independently decreased the mineralizing perimeter, mineral apposition rate, and bone formation rate. In addition, alcohol, but not hindlimb unloading, increased endocortical bone resorption. The respective detrimental effects of alcohol and hindlimb unloading to inhibit bone formation were additive; there was no interaction between the two variables. CONCLUSIONS: Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.

NASA Discipline Cell Biology↗
NASA NTRS2000

Advanced imaging of the macrostructure and microstructure of bone

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other. Copyright 2000 S. Karger AG, Basel.

NASA Discipline Musculoskeletal↗
NASA NTRS1992

Reduced vertebral bone density in hypercalciuric nephrolithiasis

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Non-NASA Center↗
NASA NTRS2016

Change in Mouse Bone Turnover in Response to Microgravity on RR-1

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1ap21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23 decrease in bone fraction (p0.005) and 11.91 decrease in bone thickness (p0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n10) and vivarium controls (n10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

bone↗
NASA NTRS2016

Changes in Mouse Bone Turnover in Response to Microgravity

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1a/p21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23% decrease in bone fraction (p=0.005) and 11.91% decrease in bone thickness (p=0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl/6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n=10) and vivarium controls (n=10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

microgravity↗
DOE OSTI2024

High-fat and high-carbohydrate diets increase bone fragility through TGF-β–dependent control of osteocyte function

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre–mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1983

A study of stress-free living bone and its application to space flight

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

Leblanc, A.↗
NASA NTRS1985

The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

Halloran, B. P.↗
NASA NTRS1984

The temporal response of bone to unloading

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Globus, R. K.↗
NASA NTRS1994

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of continuously RHLI female rats. These results suggest that PTH may be a useful agent in treatment disuse-induced osteoporosis in humans.

Ma, Y. F.↗
NASA NTRS1999

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

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Whalen, R.↗
NASA NTRS1999

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

OMalley, Bert W.↗