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At least 271 records · Page 15

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↗

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means.

Sibonga, Jean D.↗

Development and Provision of Functional Foods to Promote Health on Long-Duration Space Missions

During long-duration NASA space missions, such as proposed missions to Mars, astronauts may experience negative physiological effects such as bone loss. Functional foods such as high-lycopene, high-flavonoids and high-omega-3 products and fruits and vegetables may mitigate the negative effects of spaceflight on physiological factors including the bone health of crewmembers. Previous studies showed that current ISS provisions provide high-lycopene and high-omega-3 food items but the variety is limited, which could promote menu fatigue. Bioactive compounds can degrade like other chemical compounds and lose functionality. The native concentrations and stability of bioactive compounds have never been determined in spaceflight foods, and adequate information is not available for commercial products for the storage durations required for space exploration (5 years). The purpose of this task is to develop new spaceflight foods that are high in omega-3 fatty acids, lycopene, or flavonoids, identify commercial products with these bioactive compounds that meet spaceflight requirements, and define the stability of these nutrients in storage to enable purposeful functional food incorporation into the space food system. The impact of storage temperature on the stability of lutein, lycopene, beta-carotene, omega-3 fatty acids, phenolics, anthocyanins and sterols is being studied in 12 ISS menu items stored at three different temperatures (4, 21, 35 degree C) over 2 years. Additionally, nutrient and quality stability are being assessed on a larger food set stored at 21 degree C over 2 years that contains twelve newly developed foods, 10 commercial products repackaged to spaceflight requirements, and another 5 current ISS menu items expected to be good sources of omega-3 fatty acids, lycopene, or flavonoids. All items were shipped overnight to the Linus Pauling Institute at Oregon State University (Corvalis, OR) after processing and 1-year of storage and analyzed for bioactive compound concentrations. Sensory evaluation was conducted on the newly developed functional foods and commercial products with untrained panelists (n is greater than or equal to 25) using a 9-point Hedonic scale to test sensory attributes and overall acceptability after processing and 1-year of storage (21 degree C). Repeat nutritional and sensory analyses will be conducted in the same foods after the 2-year storage period is completed. The stability of bioactive compounds in the selected foods was dependent on storage temperature and food matrix. Omega-3 showed excellent stability in the analyzed products after 1-year of storage, regardless of the storage temperature; phenolic compounds also showed good stability. Lycopene was more stable in oil-based products rather than water-based products because of the protection that lipids offer to lycopene molecules. Also, lycopene was more stable in freeze-dried products than in high moisture foods. The 12 newly developed functional foods showed good overall acceptability in sensory attributes after processing (average score 7.2 out of 9.0) and maintained sensory quality through 1-year (21 degree C); the overall acceptability was on average 7.1 after storage. Similar behavior was observed for the 10 commercial products after 1 year. The developed products are good sources of omega-3 (both plant and marine), vegetables (7 vegetable-based products), and good sources of carotenoids, such as the Curry Pumpkin Soup and the Sweet and Savory Kale. Nine of the new products, such as Mango Salad, Pickled Beets, and Braised Red Cabbage, are rich in phenolic compounds. Stability of most of the studied nutrients seems to be adequate after 1-year of storage in most of the tested foods. However, storage temperature of the food must be considered during long-duration space missions to achieve stability of all nutrients. Likewise, more information is needed regarding nutrient retention after 2-years of storage to identify nutritional gaps that may be expected over the 5-year shelf life required for a Mars mission. New developed products will be filling a gap in the current space food system to minimize menu fatigue, provide specific nutrients to reduce the negative effects of long-duration space missions and maintain crew members' health. Information about bioactive compounds in developed products after 1-year and 2-year of storage will provide the knowledge base for further product development.

Bermudez-Aguirre, D.↗

Gene Expression and Structural Skeletal Responses to Long-Duration Simulated Microgravity in Rats

In this study, we aim to examine skeletal responses to simulated long-duration spaceflight (90 days) and weight-bearing recovery on bone loss using the ground-based hindlimb unloading (HU) model in adolescent (3-month old) male rats. We hypothesized that simulated microgravity leads to the temporal regulation of oxidative defense genes and pro-bone resorption factors, where there is a progression and eventual plateau; furthermore, early transient changes in these pathways precede skeletal adaptations.

hindlimb unloading↗

Update of the Bisphosphonate ISS Flight Experiment

The bisphosphonate study is an international collaboration between the NASA and JAXA space agencies to investigate the potential value of antiresorptive drugs to mitigate the well-established bone changes associated with long-duration spaceflight. Our hypothesis is that an antiresorptive drug in combination with in-flight exercise will ameliorate bone loss and hypercalcuria during long-duration spaceflight. We have completed data analysis for 7 crewmembers treated with alendronate during flight and 3 of 10 controls without treatment. We previously reported the pre/postflight changes in bone density and the pre versus in-flight changes in various biomarkers in crewmembers taking alendronate during flight. The purpose of this report is to compare these results with the 12- month follow-up data. The table below presents these data as a percentage change from baseline either immediately postflight or in-flight (biochemical markers) with a 1-year follow-up.

LeBlanc, Adrian↗

Skeletal Structural Consequences of Reduced Gravity Environments

The overall goal of this project is to provide structurally meaningful data on bone loss after exposure to reduced gravity environments so that more precise estimates of fracture risk and the effectiveness of countermeasures in reducing fracture risk can be developed. The project has three major components: (1) measure structural changes in the limb bones of rats subjected to complete and partial nonweightbearing, with and without treatment with ibandronate and periodic full weightbearing; (2) measure structural changes in the limb bones of human bedrest subjects, with and without treatment with alendronate and resistive exercise, and Russian cosmonauts flying on the Mir Space Station; and (3) validate and extend the 2-dimensional structural analyses currently possible in the second project component (bedrest and Mir subjects) using 3-dimensional finite element modeling techniques, and determine actual fracture-producing loads on earth and in space.

Ruff, Christropher B.↗

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.↗

An Integrated Musculoskeletal Countermeasure Battery for Long-Duration Lunar Missions

During extended periods of skeletal unloading, losses in strength and density of the proximal femur will occur. In long-duration spaceflight, resistive exercise is used to replace the normal loads exerted on the spine and hip. At the present time, there is no conclusive evidence that hip bone loss has been prevented in this scenario. Our group has recently developed and clinically evaluated a multifunctional exercise system, the Combined Countermeasure Device (CCD). The CCD comprises a low-footprint Stuart Platform for lower-body resistance exercise and balance training, and a cardiovascular exercise bicycle. A consideration for resistance exercise was targeting of the hip abductor and adductor muscles, which attach directly at the hip and which should subject it to the largest loads. In our training study, we found that CCD exercise increased hip adductor and abductor strength, and modeling results suggest that this exercise exerts forces on the hip of approx. 4-6 body weights at 1g, compared to forces of approx.2.5 body weight y squatting exercise. In our current study, we hypothesize that abductor and adductor exercise will increase the density and strength of the proximal femur.

Lang, T. F.↗

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Non-NASA Center↗

Prostaglandin E2 Restores Cancellous Bone to Immobilized Limb and Adds Bone to Overloaded Limb in Right Hindlimb Immobilization Rats

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127 to +188 percent) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels. Our findings indicate that daily 3 or 6 mg PGE2/kg/d treatment restores and maintains PTM cancellous bone mass in continuously immobilized (right) tibiae, and adds and maintains extra bone to slightly overloaded PTM cancellous bone in female rats.

Li, M.↗

Common endocrine control of body weight, reproduction, and bone mass

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

NASA Discipline Regulatory Physiology↗

The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (<10 microstrain) mechanical signals readily stimulate bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

Non-NASA Center↗

Directed Research in Bone Discipline: Refining Previous Research Observations for Space Medicine

Dual-energy X-ray absorptiometry bone mass density, as a sole index, is an insufficient surrogate for fracture; Clinical Practice Guidelines using bone mass density (both World Health Organization and FRAX) are not specific for complicated subjects such as young, healthy persons following prolonged exposure to skeletal unloading (i.e. an attribute of spaceflight); Research data suggest that spaceflight induces changes to astronaut bones that could be profound, possibly irreversible and unlike age-related bone loss on Earth.; There is a need to objectively assess factors across human physiology that are also influenced by spaceflight (e.g., muscle) that contribute to fracture risk. Some of these objective assessments may require innovative technologies, analyses and modeling.; Astronauts are also exposed to novel situations that may overload their bones highlighting a need integrate biomechanics of physical activities into risk assessments.; As we accumulate data, which reflects the biomechanical competence of bone under specific mechanically-loaded scenarios (even activities of daily living), BONE expects Bone Fracture Module to be more sensitive and/or have less uncertainty in its assessments of fracture probability.; Fracture probability drives the requirement for countermeasures. Level of evidence will unlikely be obtained; hence, the Bone Research and Clinical Advisory Panel (like a Data Safety Monitoring Board) will provide the recommendations.

Sibonga, Jean D.↗

Computational Models of Exercise on the Advanced Resistance Exercise Device (ARED)

Muscle and bone loss remain a concern for crew returning from space flight. The advanced resistance exercise device (ARED) is used for on-orbit resistance exercise to help mitigate these losses. However, characterization of how the ARED loads the body in microgravity has yet to be determined. Computational models allow us to analyze ARED exercise in both 1G and 0G environments. To this end, biomechanical models of the squat, single-leg squat, and deadlift exercise on the ARED have been developed to further investigate bone and muscle forces resulting from the exercises.

Newby, Nate↗

Characterization of Microgravity Effects on Bone Structure and Strength Using Fractal Analysis

Protecting humans against extreme environmental conditions requires a thorough understanding of the pathophysiological changes resulting from the exposure to those extreme conditions. Knowledge of the degree of medical risk associated with the exposure is of paramount importance in the design of effective prophylactic and therapeutic measures for space exploration. Major health hazards due o musculoskeletal systems include the signs and symptoms of hypercalciuria, lengthy recovery of lost bone tissue after flight, the possibility of irreversible trabecular bone loss, the possible effect of calcification in the soft tissues, and the possible increase in fracture potential. In this research, we characterize the trabecular structure with the aid of fractal analysis. Our research to relate local trabecular structural information to microgravity conditions is an important initial step in understanding the effect of microgravity and countermeasures on bone condition and strength. The proposed research is also closely linked with Osteoporosis and will benefit the general population.

Acharya, Raj S.↗

Fractal dimension analysis of weight-bearing bones of rats during skeletal unloading

Fractal analysis was used to quantify changes in trabecular bone induced through the use of a rat tail-suspension model to simulate microgravity-induced osteopenia. Fractal dimensions were estimated from digitized radiographs obtained from tail-suspended and ambulatory rats. Fifty 4-month-old male Sprague-Dawley rats were divided into groups of 24 ambulatory (control) and 26 suspended (test) animals. Rats of both groups were killed after periods of 1, 4, and 8 weeks. Femurs and tibiae were removed and radiographed with standard intraoral films and digitized using a flatbed scanner. Square regions of interest were cropped at proximal, middle, and distal areas of each bone. Fractal dimensions were estimated from slopes of regression lines fitted to circularly averaged plots of log power vs. log spatial frequency. The results showed that the computed fractal dimensions were significantly greater for images of trabecular bones from tail-suspended groups than for ambulatory groups (p < 0.01) at 1 week. Periods between 1 and 4 weeks likewise yielded significantly different estimates (p < 0.05), consistent with an increase in bone loss. In the tibiae, the proximal regions of the suspended group produced significantly greater fractal dimensions than other regions (p < 0.05), which suggests they were more susceptible to unloading. The data are consistent with other studies demonstrating osteopenia in microgravity environments and the regional response to skeletal unloading. Thus, fractal analysis could be a useful technique to evaluate the structural changes of bone.

Non-NASA Center↗

Recommended Methods for Monitoring Skeletal Health in Astronauts to Distinguish Specific Effects of Prolonged Spaceflight

NASA uses areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) to monitor skeletal health in astronauts after typical 180-day spaceflights. The osteoporosis field and NASA, however, recognize the insufficiency of DXA aBMD as a sole surrogate for fracture risk. This is an even greater concern for NASA as it attempts to expand fracture risk assessment in astronauts, given the complicated nature of spaceflight-induced bone changes and the fact that multiple 1-year missions are planned. In the past decade, emerging analyses for additional surrogates have been tested in clinical trials; the potential use of these technologies to monitor the biomechanical integrity of the astronaut skeleton will be presented. OVERVIEW: An advisory panel of osteoporosis policy-makers provided NASA with an evidence-based assessment of astronaut biomedical and research data. The panel concluded that spaceflight and terrestrial bone loss have significant differences and certain factors may predispose astronauts to premature fractures. Based on these concerns, a proposed surveillance program is presented which a) uses Quantitative Computed Tomography (QCT) scans of the hip to monitor the recovery of spaceflight-induced deficits in trabecular BMD by 2 years after return, b) develops Finite Element Models [FEM] of QCT data to evaluate spaceflight effect on calculated hip bone strength and c) generates Trabecular Bone Score [TBS] from serial DXA scans of the lumbar spine to evaluate the effect of age, spaceflight and countermeasures on this novel index of bone microarchitecture. SIGNIFICANCE: DXA aBMD is a widely-applied, evidence-based predictor for fractures but not applicable as a fracture surrogate for premenopausal females and males <50 years. Its inability to detect structural parameters is a limitation for assessing changes in bone integrity with and without countermeasures. Collective use of aBMD, TBS, QCT, and FEM analysis for astronaut surveillance could accommodate NASA's aggressive schedule for risk definition and inform a NASA-developed model which assesses the probability of overloading bones during mechanically-loaded mission tasks and possibly for physical activities after return to Earth.

Vasadi, Lukas J.↗

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

NASA Discipline Musculoskeletal↗