The modern concepts of osseous tissue changes in spaceflight.
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Aerospace Medicine↗
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Results for “Bone Demineralization, Pathologic”
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Potential effect of vitamin K on microgravity-induced bone loss.
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Administration, Oral↗
Investigation of the role of venous pressure in bone changes during prolonged weightlessness.
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Ankle↗
Changes in bone noncollagenous proteins and bone mineral loss in lumbar vertebrae of tail-suspended rats.
The purpose of the study is to clarify whether the noncollagenous proteins play a role in bone mineral loss and whether the quality of osteocalcin (OC) is deteriorated in simulated weightlessness. Noncollagenous proteins, such as OC and albumin, have been shown to be effective in promoting bone mineralization. In this study, the contents of OC, albumin, and mineral in the third lumbar vertebra (L3) were determined in rats suspended by tail for 21 days. The concentration of serum-immunoreactive osteocalcin (irOC) were also measured before and after adsorption to hydroxylapatite. The results showed that the contents of mineral, osteocalcin, and albumin in L3 were significantly decreased in suspended rats. The concentration of serum irOC and serum irOC with a high affinity to hydroxylapatite (irOCbound) were significantly decreased, but the low affinity (irOCfree) remained unaffected. The data suggest that the mineral loss in L3 of suspended rats is related to the decreased contents of osteocalcin, and albumin in bone mass. The incomplete gamma-carboxylation of osteocalcin in suspended rats is also one of the important causes of bone loss.
Albumins↗
Changes in the markers of bone metabolism following skeletal unloading.
To elucidate the mechanism in disuse bone atrophy induced by skeletal unloading, we studied the indices of bone resorption and bone formation in the femur of tail-suspended rats. The duration of the suspension ranged from 1 to 14 days. Tartrate-resistant acid phosphatase mRNA, an index used to evaluate bone resorption, increased significantly more than the controls for the first 3 days of the tail-suspension experiments, compared those in controls. Osteocalcin and alkaline phosphatase, two common markers for bone formation, were also monitored. Osteocalcin mRNA started to decrease after 3 days of suspension. Five days later, alkaline phosphatase mRNA showed a decrease. Levels of both of these mRNAs remained low for the remaining suspension period. Sequential changes in the markers for bone metabolism indicate that the transient increase in bone resorption preceded the decrease in bone formation in the development of disuse bone atrophy induced by skeletal unloading.
Acid Phosphatase↗
Prevention of bone loss and muscle atrophy during manned space flight.
This paper reviews the biomedical literature concerning human adaptation to nonterrestrial environments, and focuses on the definition of practical countermeasures necessary for long-term survival on the Moon, Mars and during long-term space missions and exploration. Of particular importance is the development of clinically relevant countermeasures for prevention of pathophysiological changes in the musculoskeletal and cardiopulmonary systems under these conditions. The countermeasures which are proposed are based upon a combination of biomechanical and theoretical analyses. The biomechanical analyses are based upon clinical measurements of human skeletal density changes associated with weight lifting as well as clinical studies of human strength and fitness currently being conducted using an isoinertial trunk dynamometer. The theoretical analysis stems from a mathematical model for bone loss in altered gravity environments that we have begun to develop. These analyses provide guidelines for the development of practical therapeutic treatments (exercise, artificial gravity) designed to minimize musculoskeletal deconditioning associated with less than Earth gravity environments. Our findings suggest that very intensive exercise, which impose high loads on the musculoskeletal system for brief periods, may be more efficient in preserving bone and skeletal muscle conditioning within "safe" limits for longer periods than low intensity activities such as treadmill running and bicycling. A 1/6 to 1/7-g gravitational environment is predicted to be sufficient to preserve bone strength above the fracture risk level. Basic biomedical support of manned space missions, Moon and Mars bases should include routine assessment of skeletal density, muscle strength, cardiac output and total energy expenditure. This information can be used to periodically re-evaluate exercise programs and or artificial gravity requirements for crew members.
Adaptation, Physiological↗
Perspective on the consequences of short- and long-duration space flight on human physiology.
During the past three decades, humans have made significant progress in accomplishing their aspirations for exploring the Moon and the planets. It is now appreciated that humans undergo a remarkable number of physiologic adaptations in microgravity that affect most physiologic systems. Space motion sickness was one of the first adaptations that humans experienced in microgravity. However, it is self-limiting and, most of the time, is effectively treated pharmacologically. Of particular concern is that, in microgravity, there is marked wasting of the skeletal musculature and skeleton that appears to be unrelenting and could impact on the health and welfare of space travelers during prolonged space flights and on return to earth. Microgravity also has a significant impact on the cardiovascular system that could have potentially serious consequences in terms of cardiovascular health during long-duration space flights. Other adaptations such as decreased T-cell responsiveness and changes in circadian rhythms is only now being explored. We need to understand the role that microgravity has on human physiologic systems in order to develop strategies for permitting humans to experience prolonged microgravity without having significant impact on their health and welfare. Engineering some gravitational force as a component of long-duration space vehicles should be given a high priority.
Adaptation, Physiological↗
The G-factor as a tool to learn more about bone structure and function.
In normal life on earth, the locomotor system is exposed to two types of stimulation: gravity (passive stimulation) and motion (active stimulation). Both permanently combine, and the interactions between locomotion and gravity induce an overall recruitment which is repeated daily and maintains the bone tissue structure within the range of constraints to which it is adapted. This range is one of the basic hypotheses underlying the mechanical concepts of bone structure control, and it has been considered as logical to assume that weightlessness of spaceflight should produce bone loss since astronauts are outside of the terrestrial gravitational field of forces, no longer relying on muscular work to change positions or move. But, thirty years after the first changes in phospho-calcium metabolism were observed in astronauts after spaceflight, current knowledge does not provide a full understanding of this pathogeny, and prove the G-factor is now considered as an essential component of the experimental tools available to study bone physiology. The study of the physiology of bone tissue usually consists in the investigation of its two fundamental roles, i.e. reservoir of inorganic elements (calcium, phosphorus, magnesium) and mechanical support for soft tissues. Together with the combined action of muscles, tendons, and ligaments, this support permits motion and locomotion. These two functions rely on a sophisticated bone tissue architecture, and on the adaptability of this structure, with modeling and remodeling processes, themselves associated with the coupled activity of specialized bone cell populations.
Animals↗
[Changes of bone cytokines and compensating regulation in tail suspended rats].
The aim of the study was to determine the relationship between the changes in bone metabolism and insulin-like growth factor--I(IGF-I) as well as epidermal growth factor (EGF). 10 Male S.D. rats were tail-suspended for 28 d with another 10 free active rats as control. The results showed that mineral content increased significantly, osteocalcin and albumin content had no significant change, but IGF-I and EGF content increased significantly in L3 in the suspended rats. The results suggest that although there are no change in osteocalcin and albumin content, the phenomenon of bone mineral loss still exists in the suspended rats. The increase in IGF-I and EGF content may be one of the compensation responses of the bone in the suspended rats.
Animals↗
[One year observation on effects of estrogen, tamoxifen combined with or without fluoride on preventing bone loss in ovariectomized rats].
OBJECTIVE: To compare the effects of one year treatment of estrogen and tamoxifen, either alone or combined with fluoride on bone metabolism in ovariectomized rats. METHODS: One hundred and forty two virgin female Sprague-Dawley rats were ovariectomized (OVX) or sham operated at 6 months of age, and randomly divided into 7 groups (19 - 21 rats each): (1) sham-operated controls; (2) OVX vehicle controls; (3) estrogen group; (4) fluoride group; (5) tamoxifen group; (6) fluoride plus estrogen; (7) fluoride plus tamoxifen. The treatments lasted for one year. Bone mineral density (BMD) measurement, bone histomorphometry analysis (lumbar vertebrae) and biomechanical test (3-point-bending test on right femur) were performed before and after treatment. The histological change of uterus were also determined at the same time. RESULTS: (1) Twelve months of ovariectomy, the OVX group had significantly lower total body (279 mg/cm(2)), lumbar vertebra (232 mg/cm(2)) than all other groups (total body 286 - 298 mg/cm(2), lumber 251 - 266 mg/cm(2), P < 0.05). Estrogen group (216 mg/cm(2)) had higher BMD than tamoxifene group (195 mg/cm(2)) in midshaft of femur. (2) After 4 months of ovariectomy, only the two combination groups kept the maximum load (145 N) of right femur over the level of OVX group (118 N); after 12 months of treatment, the maximum load of OVX group [(108 +/- 13) N] was significantly different from all other groups (132 - 155 N); both maximum load and elastic load of estrogen group were significantly higher than that of tamoxifen group. (3) No evidence of dysmineralization was found by bone histomorphometry. CONCLUSIONS: Estrogen has more potent effects on keeping bone mass and bone strength as compared with tamoxifene. The combined therapy (estrogen + fluoride or tamoxifen + fluoride) resulted in better bone strength than the single ones.
Animals↗
Effects of bisphosphonate on bone metabolism in tail-suspended rats.
Our previous studies demonstrated that tail suspension causes early, transient increases in osteoclastic activity, followed by a decrease in osteoblastic activity in the hind limbs of rats. To assess whether this early increase in bone resorption is important in the development of disuse atrophy, the effect of YH529, a third generation bisphosphonate, was studied on hind limb atrophy in rats subjected to tail suspension. YH529 (YH group) or PBS (control group) were administered subcutaneously in 5-week-old male Wistar rats suspended for 7 days. In the control group, wet weight, calcium and phosphorus contents decreased significantly in the femur but they did not change in the humerus. In the YH group, however, these parameters did not change significantly in the femur, but both calcium and phosphorus increased significantly in the humerus. These results indicate that the inhibition of bone resorption by YH529 prevents the development of disuse atrophy induced by tail suspension. It is thus suggested that early increases in bone resorption are important for the development of disuse bone atrophy.
Animals↗
Changes in serum concentrations of calcium and its regulating hormones during tail suspension in rats.
To study the effects of mechanical unloading on systemic calcium homeostasis, we determined the changes in serum concentration of calcium, 1,25-dihydroxyvitamin D3 and parathyroid hormone (PTH) during tail-suspension experiments in rats. The serum concentration of ionized calcium significantly increased during the 14 days of the suspension, reflecting increased bone resorption in the hind limbs. This hypercalcemic condition should cause suppression in PTH secretion. Indeed, serum PTH levels decreased on Day 3 of the suspension. This decrease was associated with lower serum levels of 1,25-dihydroxyvitamin [correction of dihyroxyvitamin] D3 probably due to a decrease in the activity of 1 alpha-hydroxylase in the kidneys resulting from a decrease in PTH secretion. Since it is known that 1,25-dihydroxyvitamin D3 stimulates osteoblastic function, it is suggested that endocrine responses evoked by tail suspension aggravate disuse atrophy of the hind limbs.
Amino Acids↗
Administration of bisphosphonate prevents disuse bone atrophy induced by tail suspension.
We recently demonstrated that osteopenia induced by rat tail-suspension was associated with an initial increase in bone resorption. To study the significance of the increase in early bone resorption for osteopenia, we investigated whether administration of YH529, a third-generation bisphosphonate, prevents the development of osteopenia as evidenced by increased wet weight of the femur, together with its calcium and phosphorus contents, when compared with those of tail-suspended rats treated with the vehicle alone. These results suggested that the initial increase in bone resorption plays an important role in the development of osteopenia induced by tail suspension.
Animals↗
Calcium metabolism under stress and in repose.
Derangement of calcium metabolism, although perhaps not as dramatic as that of the cardiovascular or vestibular systems, constitutes one of the major threats to the health of participants in exploration of space. On the basis of studies in immobilized subjects, the clinical disorders most likely to be encountered during prolonged space flight are primarily the consequence of an imbalance between bone formation and resorption (favoring the latter): (1) loss of skeletal mass, leading to osteoporosis; (ii) hypercalcemia; and (iii) hyper-calciuria, with the attendant risk of nephrolithiasis. By itself, loss of skeletal mass would not be expected to pose an in-flight hazard, but hypercalcemia or nephrolithiasis could jeopardize lives or mission success. Such data as are available from in-flight studies tend to support the use of immobilization as a terrestrial model for alterations in calcium metabolism during space flight. A variety of prophylactic measures have been attempted with this model in an effort to modify the observed disorders. Although there is some evidence that hypercalcemia and hypercalciuria can be reduced or prevented, negative calcium balance has not been completely reversed. Perhaps the most successful prophylactic measure utilized to date has been dietary supplementation of both calcium and inorganic phosphate. With the wide variety of excellent study tools which are currently available for application to this field, significantly increased efforts are clearly required both to define the basic mechanism of immobilization-induced skeletal losses and to devise new prophylactic or therapeutic approaches.
Astronauts↗
Countermeasure development: future research targets.
We will briefly discuss a series of countermeasures that are currently being developed to maintain bone mass and the integrity of supporting connective tissues. Our objective is to focus on several countermeasures under development which can be tested on the ISS. Other countermeasures may also be needed to provide additional safety factors which are required before long duration spaceflight is undertaken.
Biomechanical Phenomena↗
A comparative bear model for immobility-induced osteopenia.
The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.
Animals↗
[Preventive effects of exercise training on bone loss during 21 d -6 degrees head down bed-rest].
OBJECTIVE: To observe the protective effects of exercise training during 21 d -6 degrees head down bed rest (HDBR) on bone loss. METHOD: Ten healthy young men were randomly divided into HDBR group and HD-BR exercise group, with 5 in each group. Both groups were exposed to -6 degrees head down bed rest for 21 d. The subjects in the exercise group performed exercise with a bicycle ergometer in supine position 1 h/d during bed rest. Femur bone mineral density (BMD), serum bone gla protein (BGP) as well as hydroxyproline/creatinine (HOP/Cr) were determined before and during 20 d HDBR. RESULT: As compared with the before HDBR values, average femur BMD decreased by 5.8% and 0.9% for HDBR group and HDBR and exercise group respectively. HOP/Cr significantly increased in the HDBR group and was significantly higher than the HDBR exercise group. BGP decreased in both groups with no significant difference. CONCLUSION: Exercise during 21 d -6 degrees HDBR is beneficial in preventing bone loss.
Adolescent↗
The effects of microgravity on the skeletal system--a review.
Exposure of astronauts to microgravity leads to the loss of calcium from weightbearing bones. Prolonged exposure, e.g., during a journey to Mars, may present problems on return to Earth, with increased risk of fractures and premature osteoporosis in later life. The precise mechanisms of calcium loss have yet to be determined although a key feature is the absence of mechanical loading. Countermeasures aimed at reducing calcium loss to acceptable levels include the use of exercise, drugs, dietary modifications and inertia suits such as the Soviet "Penguin" suit. Missions of a number of years may, however, require the development of artificial gravity on a spacecraft. The country that first solves the physiological problems of man in space and, in particular, skeletal calcium loss, will almost certainly be the first to be able to put a man on Mars.
Adaptation, Physiological↗