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At least 235 records · Page 13

Skeletal response to corticosteroid deficiency and excess in growing male rats

The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not affect cortical bone mass. The results indicate that corticosteroid deficiency induces cancellous osteopenia, whereas supplementation with a near physiologic dose of the hormone prevents this bone loss in ADX rats. Furthermore, corticosteroid excess inhibits bone growth and bone turnover in a dose-dependent manner, but does not induce cancellous osteopenia in growing male rats.

Non-NASA Center↗

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

NASA Discipline Number 26-10↗

Nutrition in Space: Benefits on Earth

History has often proven the criticality for adequate nutrition to ensure expedition success. Space exploration will be no different, with the exception of the certainty that food will not be found along the journey. Ensuring the health and safety of astronauts is critical and nutrition will serve several functions to that end. Nutritional assessment of International Space Station (ISS) crewmembers not only serves to evaluate the nutritional health of individuals, but also allows a better understanding of how space flight affects nutritional requirements, and how nutrition can serve in mitigating the negative effects of weightlessness on the human. Available data suggest that the nutritional status of astronauts is compromised during and after flight. Inadequate dietary intake and subsequent weight loss are often considered hallmarks of space flight, although exceptions to this do exist, and provide hope. However, beyond energy intake, specific nutrient issues also exist. Several vitamins, including D and folate, are affected in space travelers. Hematological and antioxidant defense systems are impacted, with increased iron storage, and increased markers of oxidative damage. Bone loss during space flight remains a critical challenge. Ground-based studies have proven that nutrition is a potent modulator of the bone response to simulated weightlessness. Protein and sodium are two nutrients which tend to exacerbate bone resorption and loss, likely mediated through acid base balance. Defining nutrient requirements, and being able to provide and maintain those nutrients on exploration missions, will be critical for maintaining crew member health. Both flight and ground-based research provide a unique situation, one where healthy individuals are put in a unique and challenging environment. A full understanding of the role of nutrition during space flight will not only enhance crew health and safety during flight, but will also expand our understanding of the role of nutrition in health of those remaining on Earth.

Smith, Scott M.↗

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

NASA Discipline Musculoskeletal↗

The Role of Nuclear Cytoskeleton in the Osteocytic Response to Simulated Weightlessness

While in space, astronauts exercise frequently to combat bone and muscle loss due to weightlessness. This loss in bone can lead to serious health problems, such as increased fracture risk. Osteocytes are known to play a vital role in bone resorption and formation. It is also theorized that osteocytes act as the mechanosensors of bone, detecting mechanical stimulus and relaying these signals to surrounding cells. Previous research suggests that, during space flight, osteocytes exhibit matrix remodeling and resorption capabilities (osteocytic osteolysis) leading to an enlargement of the lacunae and contributing to overall bone degradation. The intercellular causes of these changes has not yet been determined. LINC or Linker of Nucleoskeleton and Cytoskeleton is a protein complex that forms a connection between the nucleus and cytoskeleton. LINC serves as a way to transmit mechanical signals to the nucleus and is also involved in the regulation of Wnt signaling via KASH proteins (Nesprin -1 and Nesprin -2). Wnt signaling in osteocytes assists with bone homeostasis and perturbed Wnt signaling can lead to bone loss. This suggests that LINC may contribute to the bone diminishing effects of microgravity. Therefore, we hypothesize that the disruption of LINC or LINC components by simulated microgravity (using the hindlimb unloading model, HU) affects Wnt signaling in osteocytes affecting bone formation and leading to increased osteocyte lacunar size. To test these hypotheses, we plan to conduct an animal study using 16 week old male mice (n6group). The mice will undergo HU for up to 7 days. After the desired time point, we will utilize quantitative real-time PCR techniques to determine the changes in gene expression of seven LINC complex genes (Sun -1, Sun -2, Nesprin -1, Nesprin -2, Lamin AC, Lamin B, and Emerin) and genes related to bone formation and osteocyte signaling. To determine changes osteocytic remodeling activity we will immunostain for osteocyte markers (Dmp-1 and Sost) and osteolysis markers (TRAP, MMPs) and measure lacunar size.

Touchstone, Hallie↗

Implementation and Integration of a Finite Element Model into the Bone Remodeling Model to Characterize Skeletal Loading

NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

bone mineral content↗

Histological and compositional responses of bone to immobilization and other experimental conditions

Histological techniques were utilized for evaluating progressive changes in tibial compact bone in adult male monkeys during chronic studies of immobilization-associated osteopenia. The animals were restrained in a semirecumbent position which reduces normally occurring stresses in the lower extremities and results in bone mass loss. The longest immobilization studies were of seven months duration. Losses of haversian bone tended to occur predominatly in the proximal tibia and were characterized by increased activation with excessive depth of penetration of osteoclastic activity. There was no apparent regulation of the size and orientation of resorption cavities. Rapid bone loss seen during 10 weeks of immobilization appeared to be due to unrestrained osteoclastic activity without controls and regulation which are characteristic of adaptive systems. The general pattern of loss persisted throughout 7 months of immobilization. Clear cut evidence of a formation phase in haversian bone was seen only after two months of reambulation.

Brown, R. J.↗

Risk of Bone Fracture due to Spaceflight-induced Changes to Bone

The Human Research Program (HRP) is taking a biomechanical approach to assessing subsequent fracture risk in active astronauts as a consequence of spaceflight exposure. Triennial testing of active and retired astronauts continues as Space Medicine monitors for a premature diagnosis of primary osteoporosis, which is associated with age-related bone loss and skeletal fragility. This updated 2023 Fracture Evidence Report has expanded the description of skeletal changes to capture the full effects of spaceflight on bone: • Recent analysis of fractures from health records of the full astronaut cohort, suggests an increased incidence rate of hip and spine fractures in astronauts following longer spaceflight duration flights compared to incident rates found in shorter duration flights. • Routine preflight-to-postflight surveillance by DXA (dual-energy x-ray absorptiometry) does not provide the full detection of loss and recovery in the long-duration (LD) astronaut nor the full recovery of hip trabecular bone. • The inclusion of hip quantitative computed tomography (QCT) in flight studies delineates effects of spaceflight, of countermeasures, and of post-flight recovery on cortical and trabecular bone parameters—some of which are verified predictors of hip fracture in the aged. • QCT detects and compares the distinct countermeasure effects of the pharmaceutical alendronate and of resistive exercise (on the Advanced Resistive Exercise Device, ARED) in specific cortical and trabecular bone sub-regions during spaceflight. • A published comparison of QCT-determined loss rates of hip trabecular bone in LD astronauts compared to terrestrial cohorts suggest that accelerated loss rates in trabecular volumetric BMD (vBMD) during spaceflight might be analogous to skeletal effects of accelerated loss rates in females due to menopause, potentially leading to disruptions in trabecular microarchitecture. • A dataset of finite element (FE) estimates of hip bone strength in aging terrestrial cohorts (spanning astronaut age-range) provides comparative context for changes in the FE of hip bone strength in LD astronauts, including comparison (force unit of newton) to percentiles (50th, 75th, and 100th) of sex-matched aged humans with hip fractures. • Risk of fracture, due to the mechanical overloading of bones, is being updated with IMPACT, the next-generation tool suite for probabilistic risk assessment (PRA) for exploration missions being created by the Exploration and Medical Capability Element (ExMC) at NASA. IMPACT is currently in development and will not be included in this 2024 update. The risk for fracture necessitates understanding the relationship between applied loads to bone and the biomechanical competence of bone. The Risk for Early Onset Osteoporosis focuses on the weakened condition of bone (including development of new technologies, measurements of novel skeletal attributes, translation of multiple measures to an index of bone fragility, and interpretations of data used to reflect a weakened bone), while the Risk for Fracture assesses factors that influence the probability an astronaut would encounter applied loads exceeding the biomechanical competence of bones, resulting in fracture. This Evidence Report combines the research gaps and tasks associated with both risks.

Fracture↗

Characterization of microgravity effects on bone structure and strength using fractal analysis

The effect of micro-gravity on the musculoskeletal system has been well studied. Significant changes in bone and muscle have been shown after long term space flight. Similar changes have been demonstrated due to bed rest. Bone demineralization is particularly profound in weight bearing bones. Much of the current techniques to monitor bone condition use bone mass measurements. However, bone mass measurements are not reliable to distinguish Osteoporotic and Normal subjects. It has been shown that the overlap between normals and osteoporosis is found for all of the bone mass measurement technologies: single and dual photon absorptiometry, quantitative computed tomography and direct measurement of bone area/volume on biopsy as well as radiogrammetry. A similar discordance is noted in the fact that it has not been regularly possible to find the expected correlation between severity of osteoporosis and degree of bone loss. Structural parameters such as trabecular connectivity have been proposed as features for assessing bone conditions. In this report, we use fractal analysis to characterize bone structure. We show that the fractal dimension computed with MRI images and X-Ray images of the patella are the same. Preliminary experimental results show that the fractal dimension computed from MRI images of vertebrae of human subjects before bedrest is higher than during bedrest.

Acharya, Raj S.↗

Pilot Study on the Investigation of Tear Fluid Biomarkers as an Indicator of Ocular, Neurological, and Immunological Health in Astronauts

The purpose of this pilot study is to investigate the collection, preparation, and analysis of tear biomarkers as a means of assessing ocular, neurological, and immunological health. At present, no published data exists on the cytokine profiles of tears from astronauts exposed to long periods of microgravity and space irradiations. In addition, no published data exist on cytokine (biomarker) profiles of tears that have been collected from irradiated non-human biological systems (primates and other animal models). A goal for the proposed pilot study is to discover novel tear biomarkers which can help inform researchers, clinicians, epidemiologist and healthcare providers about the health status of a living biological system, as well as informing them when a disease state is triggered. This would be done via analysis of the onset of expression of pro-inflammatory cytokines, leading up to the full progression of a disease (i.e. cancer, loss of vision, radiation-induced oxidative stress, cardiovascular disorders, fibrosis in major organs, bone loss). Another goal of this pilot study is to investigate the state of disease against proposed medical countermeasures, in order to determine whether the countermeasures are efficacious in preventing or mitigating these injuries. An example of an up and coming tear biomarker technology, Ascendant Dx, a clinical stage diagnostic company, is developing a screening test to detect breast cancer using proteins from tears. The team utilized Liquid Chromatography -Mass Spectrometry with Mass analysis (LC MS/MS) as a discovery platform followed by validation with ELISA to come up with a panel of protein biomarkers that can differentiate breast cancer samples from control ("cancer free") samples with results far surpassing the results of imaging techniques in use today. Continued research into additional proteins is underway to increase the sensitivity and specificity of the test and development efforts are on the way to transfer the test onto a fast, accurate and inexpensive point of care platform. In conclusion, the expected results from this proposed pilot study are to: a) establish an SOP for retrieving/storing/transporting tear fluid samples from multicentre sites b) establish a normal range for relevant biomarkers in tears; and c) establish a database (biobank) of tears of space naïve versus veteran astronauts, to establish a personal baseline for long-term ocular health monitoring

Morton, Stephen↗

Reduced vertebral bone density in hypercalciuric nephrolithiasis

Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

Non-NASA Center↗

Predicting Bone Mechanical State During Recovery After Long-Duration Skeletal Unloading Using QCT and Finite Element Modeling

During long-duration missions at the International Space Station, astronauts experience weightlessness leading to skeletal unloading. Unloading causes a lack of a mechanical stimulus that triggers bone cellular units to remove mass from the skeleton. A mathematical system of the cellular dynamics predicts theoretical changes to volume fractions and ash fraction in response to temporal variations in skeletal loading. No current model uses image technology to gather information about a skeletal site s initial properties to calculate bone remodeling changes and then to compare predicted bone strengths with the initial strength. The goal of this study is to use quantitative computed tomography (QCT) in conjunction with a computational model of the bone remodeling process to establish initial bone properties to predict changes in bone mechanics during bone loss and recovery with finite element (FE) modeling. Input parameters for the remodeling model include bone volume fraction and ash fraction, which are both computed from the QCT images. A non-destructive approach to measure ash fraction is also derived. Voxel-based finite element models (FEM) created from QCTs provide initial evaluation of bone strength. Bone volume fraction and ash fraction outputs from the computational model predict changes to the elastic modulus of bone via a two-parameter equation. The modulus captures the effect of bone remodeling and functions as the key to evaluate of changes in strength. Application of this time-dependent modulus to FEMs and composite beam theory enables an assessment of bone mechanics during recovery. Prediction of bone strength is not only important for astronauts, but is also pertinent to millions of patients with osteoporosis and low bone density.

Chang, Katarina L.↗

The Role of Calcium in Osteoporosis

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

Arnaud, C. D.↗

ECP Bone Workshop Day 2, Session 1: Validation of Exercise Countermeasures

The thesis of this session of the ECP Bone workshop is that computer modeling is required in order to evaluate factor of risk for fracture when considering the uniquely localized bone loss conditions experienced by Astronauts. This session provides an opportunity to introduce the Integrated Medical Model Bone Fracture Risk (IMM-BFxRM) simulation approach and how this and other models improve understanding of the effects of exercise countermeasures. This workshop session also provides an opportunity for the panel to provide recommendations on this and other "complex modeling" approaches, as well as, the importance of funding the IMM-BFxRM and companion efforts by external scientists (Lang and Keyak).

Myers, Jerry G.↗

Bone Biomarkers on the Pathway to Effective Spaceflight Countermeasures

Osteocyte cells are the most abundant yet least understood bone cell type in the human body. However, recent discovers in osteocyte cell biology have shed light on their importance as key mechanosensing cells regulating the bone remodeling process. Thus, we propose the first ever in vitro gene expression evaluation of osteocytes exposed to simulated microgravity to determine mechanistic pathways of their gravity sensing ability. Improved understanding of the fundamental mechanisms at the osteocyte cellular level may lead to improved treatment options to mitigate the effects of bone loss encountered by astronauts on long duration space missions and provide tailored treatment options for maintaining bone strength of immobilized/partially paralyzed patients here on Earth. Aim 1: Characterize the gene expression patterns and protein levels following exposure of murine osteocytelike cell line (MLO-Y4) to simulated microgravity using the NASA Rotating Wall Vessel (RWV) Bioreactor. Osteocytes are theorized to be the mechanosensors and transducers of mechanical load for bones, yet the biological mechanism of this action remains elusive. We propose to investigate the genetic regulation of the mechanism of the MLO-Y4 cell in the NASA Bioreactor as it is the accepted ground-based analog for simulating vector averaged microgravity.

Spatz, Jordan↗

Osteocytes Mechanosensing in NASA Rotating Wall Bioreactor

Osteocyte cells are the most abundant (90%) yet least understood bone cell type in the human body. Osteocytes are theorized to be the mechanosensors and transducers of mechanical load for bones, yet the biological mechanism of this action remains elusive. However, recent discoveries in osteocyte cell biology have shed light on their importance as key mechanosensing cells regulating bone remodeling and phosphate homeostasis. The aim of this project was to characterize gene expression patterns and protein levels following exposure of MLO-Y4, a very well characterized murine osteocyte-like cell line, to simulated microgravity using the NASA Rotating Wall Vessel (RWV) Bioreactor. To determine mechanistic pathways of the osteocyte's gravity sensing ability, we evaluated in vitro gene and protein expression of osteocytes exposed to simulated microgravity. Improved understanding of the fundamental mechanisms of mechano transduction at the osteocyte cellular level may lead to revolutionary treatment otions to mitigate the effects of bone loss encountered by astronauts on long duration space missions and provide tailored treatment options for maintaining bone strength of immobilized/partially paralyzed patients here on Earth.

Spatz, Jordan↗

Characterizing Fractures Across the Astronaut Corps: Preliminary Findings from Population-Level Analysis

Despite evidence of bone loss during spaceflight and operational countermeasures to mitigate this loss, the subsequent risk of fracture among astronauts is not known. The physiologic process of diminished bone density and bone recovery during or following spaceflight is multifactorial. Such factors as age, sex, fracture history, and others may combine to increase fracture risk among astronauts. As part of the 2016 Bone Research and Clinical Advisory Panel (RCAP), the authors analyzed data collected on 338 NASA astronauts to describe the demographics, bone-relevant characteristics, and fracture history of the astronaut population. The majority of the population are male (n=286, 84.6%), have flown at least one mission (n=306, 90.5%), and were between the ages of 30 and 49 at first mission (n=296, 96.7% of those with at least one mission). Of the 338 astronauts, 241 (71.3%) experienced a fracture over the course of their lifetime. One hundred and five (43.5%) of these 241 astronauts only experienced a fracture prior to being selected into the Astronaut Corps, whereas 53 (22.0%) only experienced a fracture after selection as an astronaut. An additional 80 astronauts (33.2%) had both pre- and post-selection fractures. The remaining 3 astronauts had a fracture of unknown date, which could not be categorized as pre- or post-selection. Among the 133 astronauts with at least one post-selection fracture, males comprised 90.2% (n=120) compared to 84.5% of the entire Corps, and females accounted for 9.8% (n=13) compared to 15.4% of the Corps. Ninety-seven of the 133 astronauts with post-selection fractures (72.9%) had one fracture event, 22 (16.5%) had two fractures, and 14 (10.5%) had three or more fractures. Some astronauts with multiple fractures suffered these in a single event, such as an automobile accident. The 133 astronauts with a post-selection fracture accounted for a total of 188 fracture events. One hundred and four (78.2%) of astronauts with post-selection fractures experienced those fractures following their first mission (mean 12.7 +/- 11.1 years following first mission; range 14.0 days - 50.6 years). Additional analyses are ongoing and include examination of fracture history, skeletal site, mechanism, and type of fracture, age at time of fracture, time from spaceflight to fracture, as well as multivariable analysis comparing fracture events to non-events. The results of such analyses may reveal trends in risk factors for fracture among the astronaut corps that have yet to be systematically described through a corps-wide approach.

Rossi, Meredith M.↗

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Review↗