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Bone mineral changes in prolonged bed rest subjects determined by gamma ray absorption technique
Electron microscope and optical birefringent studies of growth plates and metaphyseal trabeculae are described. The type and functional state of bone cells were investigated and the zone of calcification of the cartilagenous growth plate, particularly the presence and condition of matrix vesicles, was characterized. Trabecular number, size, and orientation were assessed. Comparisons with a control group, indicating changes resulting from a zero gravity situation, are presented.
Through the epidemiological analysis of bone data, HRP is seeking evidence as to whether the prolonged exposure to microgravity of low earth orbit predisposes crewmembers to an earlier onset of osteoporosis. While this collaborative Epidemiological Project may be currently limited by the number of ISS persons providing relevant spaceflight medical data, a positive note is that it compares medical data of astronauts to data of an age-matched (not elderly) population that is followed longitudinally with similar technologies. The inclusion of data from non-ISS and non-NASA crewmembers is also being pursued. The ultimate goal of this study is to provide critical information for NASA to understand the impact of low physical or minimal weight-bearing activity on the aging process as well as to direct its development of countermeasures and rehabilitation programs to influence skeletal recovery. However, in order to optimize these results NASA needs to better define the requirements for long term monitoring and encourage both active and retired astronauts to contribute to a legacy of data that will define human health risks in space.
Given that spaceflight may induce adverse changes in bone ultimate strength with respect to mechanical loads during and post-mission, there is a possibility a fracture may occur for activities otherwise unlikely to induce fracture prior to initiating spaceflight.
Total body irradiation (TBI) is a common myeloablative preparative regimen used in acute myeloid and lymphoblastic leukemia patients before allogenic hematopoietic stem cell transplantation (HSCT). The inefficient clearance of tumor cells and radiation-induced toxicity to normal tissues is attributed to relapse and morbidity in a significant fraction of patients. Developing biomarkers that indicate an individual's physiological response to radiation will allow personalized treatment and follow-up. We investigated the utility of circulating microRNA150-5p (miR150) for evaluation of radiation dose response.
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Values of mean trabecular spacing computed from optical diffraction patterns of 1:1 X-ray micrographs of tibial metaphysis and those obtained by standard image digitization techniques show excellent agreement. Upper limits on values of mean trabecular orientation deduced from diffraction patterns and the images are also in excellent agreement. Values of the ratio of mean trabecular spatial density in a region of 300 micrometers distal to the downwardly directed convexity in the cartilage growth plate to the value adjacent to the plate determined for flight animals sacrificed at recovery were significantly smaller than values for vivarium control animals. No significant differences were found in proximal regions. No significant differences in mean trabecular orientation were detected. Decreased values of trabecular spatial density and of both obsteoblastic activity and trabecular cross-sectional area noted in collateral researches suggest decreased modeling activity under weightlessness.
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The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S-ketoprofen treatment at the highest dose levels prevented the changes in cancellous bone, and reduced marrow area to increase cortical bone in the tibial shafts.
Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in osteoblasts, including increased proliferation, osteoblastic differentiation, alkaline phosphatase activity, and production of nitric oxide, prostaglandins, and osteopontin. Several proteins have been implicated in osteoblastic mechanotransduction including Bone Morphogenetic Protein-2 (BMP-2), parathyroid hormone, 1,25-dihydroxyvitamin D3 receptor, osteopontin (OPN), osteoprotegerin (OPG), and alkaline phosphatase (AP). We will characterize relative levels of each protein in mineralizing or non-mineralizing MC3T3 osteoblastic cells that have been exposed to fluid flow compared to non-fluid flow using immunofluorescent staining and two- photon laser microscopy as well as western blotting. Because calcium-mediated pathways are important in osteoblastic signaling, we will transfect MC3T3 cells with cameleon probes for Ca2+ containing YFP and CFP. Results will be analyzed using FRET/FLIM to study differential release of intracellular Ca(2+) in response to fluid flow and conditions inducing matrix mineralization. In addition, we plan to conduct several microarray experiments to determine differential gene expression in MC3T3 cells in response to fluid flow and conditions inducing mineralization.
This proposal addresses the need for effective and innovative science and health education materials that focus on space bone biology and its implications for bone health on Earth. The focus of these materials, bone biology and health, will increase science knowledge as well as health awareness. Current investigations of the bone loss observed after long-duration space missions provide a link between studies of bone health in space, and studies of osteoporosis, a disease characterized by bone loss and progressive skeletal weakness. The overall goal of this project is to design and develop web-based and print-based materials for high school science students, that will address the following: a) knowledge of normal bone biology and bone biology in a microgravity environment; b) knowledge of osteoporosis; c) knowledge of treatment modalities for space- and Earth-based bone loss; and d} bone-related nutrition knowledge and behavior. To this end, we propose to design and develop a Bone Biology Tutorial which will instruct students about normal bone biology, bone biology in a microgravity environment, osteoporosis - its definition, detection, risk factors, and prevention, treatment modalities for space- and Earth-based bone loss, and the importance of nutrition in bone health. Particular emphasis will be placed on current trends in . adolescent nutrition, and their relationships to bone health. Additionally, we propose to design and develop two interactive nutrition/health ' education activities that will allow students to apply the information provided in the Bone Biology Tutorial. In the first, students will apply constructs provided in the Bone Biology Tutorial to design "Bone Health Plans" for space travelers.