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At least 37 records · Page 2

The Effect of Skeletal Unloading on Bone Formation: Role of IGF-I

The best documented change in bone during space flight is the near cessation of bone formation. Space flight leads to a decrease in osteoblast number and activity, likely the result of altered differentiation of osteoblast precursors. The net result of these space flight induced changes is weaker bone. To understand the mechanism for these changes poses a challenge. Space flight studies must overcome enormous technical problems, and are necessarily limited in size and frequency. Therefore, ground based models have been developed to evaluate the effects of skeletal unloading. The hindlimb elevation (tail suspension) model simulates space flight better than other models because it reproduces the fluid shifts seen in space travel, is reversible, and is well tolerated by the animals with minimal evidence of stress as indicated by continued weight gain and normal levels and circadian rhythms of corticosterone. This is the model we have used for our experiments. Skeletal unloading by the hindlimb elevation method simulates a number of features of space flight in that bone formation, mineralization, and maturation are inhibited, osteoblast number is decreased, serum and skeletal osteocalcin levels fall, the ash content of bone decreases, and bone strength diminishes. We and others have shown that when osteoblasts or osteoprogenitor cells from the bones of the unloaded limbs are cultured in vitro they proliferate and differentiate more slowly, suggesting that skeletal unloading causes a persistent change in cell function which can be assessed in vitro. In contrast to the unweighted bones of the hindlimbs, no significant change in bone mass or bone formation is observed in the humeri, mandible, and cervical vertebrae during hindlimb elevation. The lack of effect of hindlimb elevation on bones like the humeri, mandible, and cervical vertebrae which are not unloaded by this procedure suggests that local factors rather than systemic effects dominate the response of bone to skeletal unloading. We have focussed on the role of IGF- 1 as the local factor mediating the effects of skeletal unloading on bone formation. IGF-I is produced by bone cells and chondrocytes; these cells have receptors for IGF-I, and respond to IGF-I with an increase in proliferation and function (e.g. collagen, and glycosaminoglycan production, respectively). IGF-I production by bone is under hormonal control, principally by GH and PTH, and IGF-I is thought to mediate some if not all of the effects of GH and PTH on bone growth. Thus, systemic changes in hormones such as GH and PTH may still have effects which vary from bone to bone depending on the loading history.

Bikle, D. D.↗

[Clinical and physiological evaluation of bone changes among astronauts after long-term space flights]

Results of the joint Russian/US studies of the effect of microgravity on bone tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in the whole body, the scalp including cervical vertebra, arms, ribs, sternal and lumbar regions of the spinal column, pelvis and legs. A clearly defined dependence of topography of changes upon the position of a skeletal segment in the gravity vector was established. The greatest BMD losses have been observed in the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged (insignificant) or showed a positive trend. Overall changes in bone mass of the whole skeleton of male cosmonauts during the period of about 6 months on mission made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of cosmonauts' bone tissues as local osteopenia. On the literature and results of authors' clinical evidence, discussed is availability of the densitometric data for predicting risk of trauma. A biological nature of the changes under observation is hypothesized.

NASA Discipline Musculoskeletal↗

Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group

Among 2992 white women aged 65-70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5-L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity greater than or equal to 4 SD. Vertebral deformities less than 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was greater than or equal to 4 SD had a 1.9 (95% CI, 1.5-2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7-3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0-3.2) times more likely to have lost greater than or equal to 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities less than 4 SD did not increase the likelihood of these three outcomes, but multiple deformities greater than or equal to 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.

Non-NASA Center↗

Histomorphometric analysis of rat skeleton following spaceflight

Male Sprague-Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared with data derived from ground-based control rats. Trabecular bone mass was not altered during the 1st wk of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. For the most part, histological indexes of bone resorption were normal in flight rats. The results indicate that 7 days of weightlessness are not of sufficient duration to induce histologically detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the 1st wk of spaceflight.

Non-NASA Center↗

Fragility and composition of growing rat bone after one week in spaceflight

To gain some insight into the early effects of spaceflight on skeletal metabolism, we quantified the major chemical constituents and a noncollagenous protein, osteocalcin, in the third-lumbar vertebrae and humeri from 8-wk-old rats that were part of the 7-day NASA Spacelab 3 flight experiments. The ratio of calcium to hydroxyproline in the humeral diaphysis increased from 8.5 in preflight to 9.8 in ground simulation control and only to 8.9 in flight bones. There was no demonstrable change in the fraction of nonmineralized collagen. Osteocalcin content was reduced in the humerus and vertebra. Reduced accumulation of mineral and osteocalcin with no associated decrease in collagen in flight animals suggests that both mineralization and collagen metabolism are impaired in growing animals during spaceflight within a few days after launch. Strength tests of the humeri of flight rats showed substantial deficits that appeared to be related, not only to the reduced bone mass, but also to the composition and quality of new bone formed.

STS-51B Shuttle Project↗

Ultrasound Imaging of Spine: State of the Art and Utility for Space Flight

Introduction: Ultrasound imaging (sonography) has been increasingly used for both primary diagnosis and monitoring of musculoskeletal injury, including fractures. In certain injuries, sonography has been shown to equal or surpass Magnetic Resonance Imaging in accuracy. Long-term exposure to reduced gravity may be expected to cause physiological and anatomical changes of the musculoskeletal system, which are not fully described or understood. In a limited-resource environment like space flight, sonography will likely remain the only imaging modality; therefore, further attention to its potential is warranted, including its ability to image anatomical deviations as well as irregularities of vertebrae and the spinal column. Methods: A thorough review of literature was conducted on the subject. A multipurpose ultrasound system was used to identify specific vertebrae, intervertebral disks, and other structures of the cervical spine in healthy volunteers, selected to represent various age, gender, and Body Mass Index (BMI) groups. Sonographic views were sought that would parallel radiographic views and signs used in the diagnosis of cervical spine injuries. Results: While using widely accepted radiographic signs of cervical spine injury, this sonographic protocol development effort resulted in successful identification of scanning planes and imaging protocols that could serve as alternatives for radiography. Some of these views are also applicable to diagnosing degenerative disk and bone disease, and other non-traumatic spine pathology. Strong, preliminary correlation has been demonstrated in a number of clinical cases between sonography and other imaging modalities. Conclusion: In the absence of radiography, sonography can be used to diagnose or rule out certain common types of cervical spine conditions including injury. Clinical validation of the findings appears to be realistic and would facilitate establishment of new sonographic protocols for special environments with lacking radiographic capability, such as human space flight.

Sargsyan, Ashot E.↗

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

Sibonga, J. D.↗

Numerical Investigation of Occupant Injury Risks During A Realistic Transport Aircraft Crash Conditions

Researchers at the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) have conducted a full-scale crash test of a Fokker F28 MK1000 aircraft to investigate the performance of transport aircraft under realistic crash conditions. This crash test was computationally recreated using finite element (FE) human body models (HBMs) to further explore potential injury risks to occupants and analyze the utilization of HBMs in the aerospace crash environment. The Global Human Body Model Consortium (GHBMC) male 50th percentile occupant detailed model (v6.0) and the Toyota Human Model for Safety (THUMS) male 50th percentile occupant model (v6.1) were selected to be used in the crash simulations. The HBMs were simulated in conditions matching those of anthropomorphic test device (ATD) experiments included within the aircraft cabin during the crash test. Seven occupant locations within the cabin were simulated utilizing each of the models. The models were positioned in a neutral upright posture with hands resting on the legs and the feet contacting the floor. Head, brain, neck, and lumbar vertebra injury metrics were calculated for all trials. Both HBM models required minor modifications to stabilize these simulations. The GHBMC model required added erosion for six parts while the THUMS model only required one in order to complete the full simulation. The THUMS model, however, required a much smaller timestep for stability and therefore took significantly more computational time. In addition the GHBMC model includes integrated instrumentation while the THUMS model requires development and implementation of instrumentation. Both models predicted 100% injury risk for lumbar vertebra fracture in all test conditions. This prediction was in family with high lumbar load values measured by the ATDs during the crash test. The THUMS model consistently predicted lower injury risks than the GHBMC model in all three other metrics varying depending on the crash pulse. Overall, the THUMS model required less modifications to allow for this study. However, the GHBMC models significantly faster run time and integrated instrumentation make it a more intuitive model for this research.

Crashworthiness↗

37-Day Microgravity Exposure in 16-Week Female C57BL/6J Mice is Associated with Weight Bearing Site-Specific Bone Loss

Exposure to space environment factors, including microgravity unloading and space radiation, is well-known to be associated with rapid bone loss in mammals, but significant questions remain about mechanistic aspects of this process. Specifically, bone loss may vary depending on many interacting factors including age and skeletal maturity, physical activity, social versus individual housing, and habitat configuration. Likewise cellular tissue loss mechanisms in space may include changes to mineral homeostasis by activation of bone degradation by osteoclasts, or inhibition of bone formation by osteoblasts, and be caused by microgravity mechanical unloading or increased space radiation. In this study we used microcomputed tomography to quantify bone loss in multiple skeletal sites of group housed mice either exposed to 37 days in space on ISS during the Rodent Research 1, (RR1), experiments using the NASA Rodent Habitat, (RH), versus ground controls in the same habitats or standard vivarium cages. Our results in space versus matched RH ground controls show significant cancellous and cortical bone loss in the femur and tibia, but not in vertebrae, indicating that only weight-bearing bones experience significant bone loss during spaceflight. This finding suggests that space radiation at the low levels found in low Earth Orbit may not be a significant contributing factor to bone loss in space. Interestingly while mice maintained in the RH maintained or gained bone relative to Basal controls, mice kept in standard vivarium cages for 37 days showed significant loss in weight bearing bones, not as acute, but comparable in magnitude to spaceflight effects. These results suggest the RH configuration versus vivarium cages, may allow for greater mechanical loading of weight bearing bones as mice climb internal habitat surfaces, promoting maintenance of bone regenerative health.

mouse↗

The investigation of vertebral injury sustained during aircrew ejection

A series of tests were performed on excised human vertebral segments to determine the static and dynamic response of the thoraco-lumbar spine when loaded in flexion. A total of fifteen tests were performed on eleven specimens. Specimens were obtained from male donors ranging in age from 34 to 60 years. Demographic data pertinent to each specimen and the elapsed time between death of the donor and testing of each corresponding specimen are presented. Only spinal segments comprised of lower thoracic and upper lumbar vertebrae were tested because in aircraft ejection injuries clinical complications in this anatomical region predominate. A complex continuum mathematical model describing the dynamic response of the human spine was formulated, solved, and verified experimentally. Detailed results are presented in figures, tables, and equations.

Benedict, J. V.↗

Ash content of bones in the pigtail monkey, Macaca nemestrina.

Ash analyses of skeletons of four adult primates, Macaca nemestrina, revealed some similarities and some marked contrasts when compared with published data on human skeletal ash. The skull in both Macaca nemestrina and man has the highest ash content of all bones in the skeleton. While the bones of the arms of humans have an ash content nearly identical to that of the legs (0.3% difference), in Macaca nemestrina the humeri and radii contain 5.4% more ash than the femora and tibiae. Similarly in Macaca nemestrina the bones of the hands contain 3.5% more ash than the bones of the feet, while in humans the same bones agree within 0.3% implying that adaptive use function is a factor in bone ash concentration. The ribs of Macaca nemestrina showed an unexpectedly high ash content in comparison with those of humans. In contrast with the relatively constant ash content throughout the vertebrae in humans, a conspicuous decrease axially was noted in Macaca nemestrina.

Vose, G. P.↗

Intrathoracic and venous pressure relationships during responses to changes in body position

Simultaneous end-expiratory pressures, referred to midthoracic level, in the superior and abdominal venae cavae, pericardial space, and right and left heart, were recorded without thoracotomy in three anesthetized dogs during sudden changes from supine to vertical head-up or head-down body positions. Intrathoracic and dependent great vein pressures referred to midchest level (sixth thoracic vertebra) decreased and showed simple hydrostatic gradients in either vertical position. However, a discontinuity in the large vein hydrostatic gradient occurred just distal to the superior margin of the thorax in either body position and was resumed again above this level. It is concluded that, just as the cerebrospinal fluid and intraperitoneal pressures minimize the effects of gravitational and inertial forces on the cerebral and visceral circulations, the pericardial and pleural pressures have a similar role for the heart proper.

Avasthey, P.↗

Applications of the direct photon absorption technique for measuring bone mineral content in vivo. Determination of body composition in vivo

The bone mineral content, BMC, determined by monoenergetic photon absorption technique, of 29 different locations on the long bones and vertebral columns of 24 skeletons was measured. Compressive tests were made on bone from these locations in which the maximum load and maximum stress were measured. Also the ultimate strain, modulus of elasticity and energy absorbed to failure were determined for compact bone from the femoral diaphysis and cancellous bone from the eighth through eleventh thoracic vertebrae. Correlations and predictive relationships between these parameters were examined to investigate the applicability of using the BMC at sites normally measured in vivo, i.e. radius and ulna in estimating the BMC and/or strength of the spine or femoral neck. It was found that the BMC at sites on the same bone were highly correlated r = 0.95 or better; the BMC at sites on different bones were also highly interrelated, r = 0.85. The BMC at various sites on the long bones could be estimated to between 10 and 15 per cent from the BMC of sites on the radius or ulna.

Cameron, J. R.↗

Prediction of femoral neck and spine bone mineral content from the BMC of the radius or ulna and the relationship between bone strength and BMC

The bone mineral content (BMC) is extensively used to provide information about the status of an entire skeleton. Changes in BMC are employed to evaluate the effect of various drugs, disease states, weightlessness, exercise, renal dialysis and others on the skeleton. Clinical and functional information is discussed that may be derived from the BMC of a limited region of the skeleton. In particular there is a fairly high degree of correlation between the BMC of the radius or ulna and that of the femoral neck, r about 0.85 and a somewhat lower relationship between the BMC of the radius or ulna and the thoracic vertebrae, r about 0.65. Also the BMC is highly related to the strength of bone at that scan site.

Wilson, C. R.↗

Effect of space flight on sodium, copper, manganese and magnesium content in the skeletal bones

Sodium content decreased in the human skeletal bones and rose in the rat bones following space flight. In man copper content rose in the femoral bone and decreased in the vertebral body and the sternum, but was unchanged in the rest of the bones. Magnesium content was decreased in the femoral bone and the sternum, and in the vertebrae, but remained unchanged in the rest of the bones. Possible mechanisms of the changes detected are discussed.

Prokhonchukov, A. A.↗

The combined effects of ionizing radiation and weightlessness on calcium and phosphorus content in the mineral fraction of the calcified tissues in the rat skeleton

Phosphorus and calcium content in the ash from skeletal bones (ribs, scapula, vertebra, and crus) of 30 rats exposed to ionizing radiation (800 rads) on the flight of the Kosmos 690 biosatellite was studied. A 10 percent decrease in ash content coefficient and 29 percent decrease in phosphorus content was found immediately after the flight, and a 9 percent decrease in phosphorus content persisted after 26 days of readaptation to terrestrial conditions.

Prokhonchukov, A. A.↗

A 14-day ground-based hypokinesia study in nonhuman primates: A compilation of results

A 14 day ground based hypokinesia study with rhesus monkeys was conducted to determine if a spaceflight of similar duration might affect bone remodeling and calcium homeostatis. The monkeys were placed in total body casts and sacrificed either immediately upon decasting or 14 days after decasting. Changes in vertebral strength were noted and further deterioration of bone strength continued during the recovery phase. Resorption in the vertebrae increased dramatically while formation decreased. Cortical bone formation was impaired in the long bones. The immobilized animals showed a progressive decrease in total serum calcium which rebounded upon remobilization. Most mandibular parameters remained unchanged during casting except for retardation of osteon birth or maturation rate and density distribution of matrix and mineral moieties.

Kazarian, L.↗