The investigation of the bone system and body composition in the participants of the Mars-500 experiment (prior to and on completion of the experiment) employed dual-energy X-ray absorptiometry (DXA) using a HOLOGIC Delphy osteodensitometer according to the protocol used in examination of cosmonauts. The bone density of lumber vertebrae and femoral proximal epiphysis, as well as the body composition were measured. Statistically significant changes in the mineral density of lumber vertebrae were found in three subjects and displayed different trends from +2.6 to –2.4%. At the same time, in the femoral proximal epiphysis, including in the cervical region, the mineral density after the experiment was significantly lower in all participants. Four subjects exhibited an increase (by 5–9%) in the mineralization of the skull bones, as in some cosmonauts after flights. All participants were characterized by loss of adipose tissue mass (from 2 to 7 kg; in one subject, 20 kg, by a factor of three). Changes in lean mass (by 1–3 kg) were often negative and in the limbs might be associated with preferences for a certain type of physical activity. It is shown that prolonged stay in a confined space can lead to a decrease in mineralization of individual parts of the skeleton. Unlike real spaceflights and long-duration experiments with hypokinesia carried out earlier at the Institute for Biomedical Problems, no clinically significant loss of mineral density (osteoporosis, osteopenia) was observed in the Mars-500 experiment, which may be due to the lack of microgravity effects.

Analysis of the results of long-term investigations of bones in cosmonauts on board Mir orbital station(OS) and International Space Station (ISS) (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to be correlated (r = 0.904) with the position relative to Earth’s gravity vector. Vector dependence of bone loss results from local specificity of expression of bone metabolism genes, which reflects mechanical prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss, which is attested by the dependence of bone loss rate on polymorphism of certain genetic markers of bone metabolism. The type of the orbital vehicle did not affect the individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-specific spatial structure of distribution of non-collagen proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotropic intervention into areas of bustling resorption.

Comparison of bone mineral density and fatty acid (FA) blood content in nine subjects during 370-day head-down-tilt bed rest (BR) revealed correlation of the loss of femoral neck density (FND) with parameters of lipid metabolism. On day 46 of the BR, the absolute lipid content of erythrocyte membranes and blood serum were considerably decreased (by a factor of 1.5–2) compared with the baseline data. At the end of the experiment, on the contrary, the lipid content of serum was two to three times higher than the baseline value; however, the lipid content of erythrocyte membranes remained decreased in the control group until day 280 of the BR. The arachidonic acid concentration was correlated with those of prostaglandins PGE2 and PDF2α involved in the regulation of osteoclast and osteoblast activities. The mutually correlated patterns of decrease in FND and unsaturated FA contents of blood serum and erythrocyte membranes exhibited individual specificity.

The densitometry of cosmonauts after long-term missions shows a reduction of bone mineral density (BMD). On average, the postflight BMD remains within the normal range and the broad variability of individual BMD values is sometimes regarded as local osteopenia. Individual reactions are classified by the similarity of amount and rate of BMD loss.

Densitometry of cosmonauts following long duration missions revealed different types of site specific changers of human skeleton. So, theoretically, the expected a decrease in bone mass according with gravity vector reflected the local specificity of bone genes expression connected with the mechanical history of Homo erectus evolution. High individual variability of bone mass changes may be a manifestation of genetic polymorphism. We show the individual stability of bone mass changes at different sites of skeleton after repetitive spaceflights. This phenomenon may be considered as an illustration of phenotypical characteristics of local bone metabolism in the form of specific for this locus spatial structure of non-collagenic proteins distribution.

The long-term research of human skeletal system during spaceflight on the orbital station Mir and International Space Station (ISS) was summarized. The amount of bone mass and body composition was measured using a noninvasive method, dual-energy X-ray absorbtiometry (DXA) or osteodensitometry. Theoretically expected loss of bone mass in tubular structures of the lower part of the body during space flight with a duration of five to seven months is described by the phenomenon of fast-developing but reversible osteopenia and is considered a manifestation of functional adaptation of bone tissue to the changing mechanical load on the skeleton. A high individual variability of changes and stability of individual nature of the ratio of bone mass changes in different segments of the skeleton independently of the type of orbital station has been demonstrated. A strict dependence of bone mass changes on the flight duration cannot be established, and there are no grounds for calculating the probability of reaching the critical level of demineralization for the duration of flight increased to 1.5–2 years. There is even less probability to predict changes in bone structure (quality), which, together with the loss of bone mass, determine the risk of fracture. The data indicating that the DXA method is insufficient for such prognosis are presented. The main areas of research that would optimize the development of the project of interplanetary mission in terms of preservation of the mechanical function of the skeleton are considered.

The results of long-term investigations of the bone system of humans during space flights (SFs) on board the Mir orbital station (OS) and international space station (ISS) using osteodensitometry are summarized. Comparative analysis of the results showed the absence of significant differences in changes in the bone mass (BM) in the crew members of both OSs. Theoretically, the expected bone mass losses in the trabecular bone structures of the lower part of the body in the process of a SF (five to seven months) are interpreted in some cases as quickly developing, but reversible, osteopenia and generally interpreted as the evidence of bone functional adaptation to altering mechanical loads on the skeleton. The high individual variability of changes and the stability of the individual character of the BM alteration ratio in different skeletal segments irrespective of the OS type are shown. Owing to the aforementioned individual features, it is not possible to establish a strict relationship between BM changes and the duration of space missions, and, therefore, there is no good reason for calculating the probability of achieving the critical demineralization level when the duration of an SF increases to 1.5–2 years. The probability of prediction of changes in the bone quality (structure) is still less, which, together with BM losses, determines the risk of fractures, and osteodensitometry for such an analysis is insufficient. The main directions of the studies, which could optimize the development of the interplanetary expedition project from the point of view of maintenance of the mechanical function of the skeleton, are considered.

A summary of investigations results of human bone tissue changes in space flight on the orbital station (OS) Mir and international space station (ISS) using dual energy X-ray absorptiometry (DXA) is given. Results comparative analysis revealed an absence of significant differences in bone mass (BM) changes on the both OS. Theoretically expected BM loss was observed in bone trabecular structure of skeleton low part after space flight lasting 5-7 month. The BM losses are qualified in some cases as quicly developed but reversible osteopenia and generally interpreted as evidence of bone functional adaptation to the alterating mechanical loading. It was demonstrated the high individual variability BM loss amplitudes. Simultaneously was observed the individual pattern of BM loss distribution across different segments of skeleton after repetitive flights independently upon type of OS. In according with the above mentioned individual peculiarities it was impossible to establish the dependence of BM changes upon duration of space missions. Therefore we have not sufficiently data for calculation of probability to achive the critical demineralization level by the augmentation the space mission duration till 1.5-2 years. It is more less possibility of the bone quality changes prognosis, which in the aggregate with BM losses determines the bone fracture risk. It become clearly that DXA technology is unsuffitiently for this purpose. It is considered the main direction which may optimized the elaboration of the interplanetary project meaning the perfectly safe of skeleton mechanical function.

The results of long-standing investigations of the human bone system in the piloted Mir and International space station missions were reviewed. The noninvasive DXA technology was used to determine bone mass (BM) and body composition. Predictable BM losses in the lower body tubular bones during 5 to 7-mo. space missions are characteristic of rapid but recoverable osteopenia and viewed as functional adaptation to altering mechanic loading of the skeleton. These changes feature high individual variability. Interestingly, the extent of BM changes in different segments of the skeleton displays stability in individual crew members irrespective of space station design. No strong dependence of BM changes on flight duration has been established and, therefore, calculation of the probability of critical bone demineralization after 1.5 to 2 years in space flight is impractical. Still less is the possibility to predict impairment of the bone structure which, together with BM losses, preconditions the risk of fracture. The data presented witness DXA inadequacy for such prediction. Main areas of researches toward optimization of the exploration mission design and planning in the context of the skeleton mechanic function maintenance are considered.

The association of the polymorphism of the VDR, Col1a1 , and CALCR genes with a form of osteoporosis frequently occurring as a consequence of intense physical exercise in athletes was studied. Biochemical parameters of bone remodeling and its neuroendocrine regulation, as well as the bone masses, of 22 amateur athletes were determined immediately before a strenuous nine-week training cycle (TC) and eight months later. The possible association of these factors with the polymorphism of the genes coding for bone tissue proteins was studied. Long-term intense physical training was found to be associated with a significant activation of bone tissue resorption accompanied by continued rapid synthesis. Nevertheless, and in spite of the strong activation of resorption caused by the TC, the athletes exhibited no osteoporosis (even eight months after the discontinuation of the TC); some of them, however, displayed an individual tendency to osteopenia. According to the results of genetic analysis, this was associated with the polymorphism of predisposition genes (genotype TT of the VDR gene and the functionally weakened s allele of the Col1a1 gene).

A summary of results of investigations by the author and a brief review of some literature data on human bone tissue deprived of mechanical loading (spaceflight, hypokinesia) is given. The direction and markedness of changes in bone mass-the bone mineral density and the bone mineral content-in different skeletal segments depend on their position relative to the gravity vector. A theoretically expected bone mass reduction was revealed in the trabecular structures of the bones of the lower part of the skeleton and in some cases was qualified as local osteopenia. In the upper part of the skeleton, an increase in the bone mineral content is observed, which is considered as a secondary response and is due to redistribution of body fluids cephalad. The main cause of osteopenia is mechamcal unloading. Arguments are presented that osteocyte osteolysis, delayed osteoblast histogenesis. And osteoclast resorption provoked by rearrangement in the hierarchy of the systems of volume regulation, ion regulation, and the endocrine regulation of calcium homeostasis are the main mechanisms of osteopenia.

До и после интенсивных силовых тренировок (9 недель) по трём различным протоколам у 22 спортсменов-любителей изучали: изменения биохимических маркёров костного ремоделирования, его нейроэндокринную регуляцию, костную массу до и после тренировочного цикла (ТЦ). Установлено, что длительная интенсивная физическая нагрузка сопряжена со значительной активацией процессов резорбции костной ткани в сочетании с сохранением высокого уровня синтетических процессов. Тем не менее сравнительно короткая продолжительность экспериментальных тренировок, как и следовало ожидать, не выявила их существенного влияния на показатели МПК всех исследованных участков скелета. Обнаруженные слабо выраженные тенденции могут рассматриваться как случайные флюктуации, не выходящие за пределы технической точности

The review deals with the analysis of osteodensitometry data from the cosmonauts flown on Russian space station MIR and the International space station and suppositions about involvement of different levels of metabolism regulation in bone loss triggered by insufficient mechanic loading in microgravity attendant by redistribution of body liquids. It is surmised that the initial reactions are associated with the biomechanical factor and recruitment of local mechanisms, i.e. osteocyte osteolysis and inhibition of osteoblast histogenesis. Regulation on the level of tissues and organs is responsible for destabilization of calcium homeostasis (low calcium absorption in the intestine and readsorption in the kidney). Changes in the hierarchy of ion and volume regulation may provoke osteoclast resorption which further increases osteopenia.

The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD), with dual-energy X-ray absorptiometry (DXA) before and after flight, of astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight.Our analysis was supplemented by BMD data from cosmonauts (by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members a small number of whom flew on more than one mission - were used in this analysis. Changes in BMD (between 56 different sets of pre- and postflight measurements) were Plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: (i) BMD change on landing day (day 0) and (ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2% and 9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months. (C) 2007 Elsevier Inc. All rights reserved.

Hypothesized processes of changes found in spacecrew bones following 5 to 7 mo. orbital missions are reviewed. Selective osteopenia of trabecular bones in the lower skeleton is attributed to a greater weight loading at 1 g. Increased mineral content in the upper skeleton (dual energy X-ray adsoptiometry--DXA) and hypermineralization of the limbic spongious bone (computer tomography) appear to be secondary and reflect the body liquids redistribution headword including to the abdomen. The additional negative gradient of the lower skeleton mass during early readaptation (about 1.5 mo, after landing) can be explained by remodeling (resorption and bone formation) as a reaction to the "load return". Personal variability is probably a fingerprint of genetic determinism of bone mass and metabolic phenotype that may sometimes lead to an increased risk of fracture. The authors raise the discussion about practicality of the genetic osteopenia prediction for space flyers.