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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS2009

A Biomechanical Approach to Assessing Hip Fracture Risk

Bone loss in microgravity is well documented, but it is difficult to quantify how declines in bone mineral density (BMD) contribute to an astronaut's overall risk of fracture upon return. This study uses a biomechanical approach to assessing hip fracture risk, or Factor of Risk (Phi), which is defined as the ratio of applied load to bone strength. All long-duration NASA astronauts from Expeditions 1-18 were included in this study (n=25), while crewmembers who flew twice (n=2) were treated as separate subjects. Bone strength was estimated based on an empirical relationship between areal BMD at the hip, as measured by DXA, and failure load, as determined by mechanical testing of cadaver femora. Fall load during a sideways fall was calculated from a previously developed biomechanical model, which takes into account body weight, height, gender, and soft tissue thickness overlying the lateral aspect of the hip that serves to attenuate the impact force. While no statistical analyses have been performed yet, preliminary results show that males in this population have a higher FOR than females, with a post- flight Phi of 0.87 and 0.36, respectively. FOR increases 5.1% from preflight to postflight, while only one subject crossed the fracture "threshold" of Phi = 1, for a total of 2 subjects with a postflight Phi > 1. These results suggest that men may be at greater risk for hip fracture due largely in part to their relatively thin soft tissue padding as compared to women, since soft tissue thickness has the highest correlation (R(exp 2)= .53) with FOR of all subject-specific parameters. Future work will investigate changes in FOR during recovery to see if baseline risk levels are restored upon return to 1-g activity. While dual x-ray absorptiometry (DXA) is the most commonly used clinical measure of bone health, it fails to provide compartment-specific information that is useful in assessing changes to bone quality as a result of microgravity exposure. Peripheral quantitative computed tomography (pQCT) accomplishes this by imaging transverse "slices" of the long bones. This project was a re-analysis of a 90 day bed rest study to determine if changes to cortical and trabecular compartments could be detected in the distal tibia with statistical significance using a new pQCT image analysis method. Nearly all changes in bone mineral density (BMD) and cross sectional area (CSA) measures were seen with statistical significance, with the exception of a change in cortical BMD. Total bone CSA increased by 1.1 % (p =0.01), cortical CSA decreased by - 5.6% (p<0.001) and trabecular CSA increased by 1.76% (p=0.007); the combination of which suggests bone resorption occurred at the endocortical surface in response to mechanical unloading by bed rest. Furthermore, total BMD and trabecular BMD decreased (-3.8%, p=0.001 and -2.8%, p =0.007, respectively), while decreases in cortical BMD failed to reach significance (-1.2%, p=0.07). Given that compartment-specific changes are seen with significance and are likely to influence bone strength, it is recommended that pQCT remain a standard measure used in bed rest because it provides a unique measure by which to better evaluate the efficacy of countermeasures to microgravity-induced bone loss.

Ellman, Rachel↗
DOE OSTI2017

Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells

Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors. These effects predominantly occurred via RARγ and were further enhanced by an RARα agonist or antagonist, respectively. RAR agonists similarly impaired adipogenesis in osteogenic cultures. RAR agonist treatment resulted in significant upregulation of the Wnt antagonist, Sfrp4. This accompanied reduced nuclear and cytosolic β-catenin protein and reduced expression of the Wnt target gene Axin2, suggesting impaired Wnt/β-catenin signalling. To determine the effect of RAR inhibition in post-natal mice, IRX4310 was administered to male mice for 10 days and bones were assessed by µCT. No change to trabecular bone volume was observed, however, radial bone growth was impaired. These studies show RARs directly influence osteoblast and adipocyte formation from mesenchymal cells, and inhibition of RAR signalling in vivo impairs radial bone growth in post-natal mice. - Graphical abstract: Schematic shows RAR ligand regulation of osteoblast differentiation in vitro. RARγ antagonists±RARα antagonists promote osteoblast differentiation. RARγ and RARα agonists alone or in combination block osteoblast differentiation, which correlates with upregulation of Sfrp4, and downregulation of nuclear and cytosolic β-catenin and reduced expression of the Wnt target gene Axin2. Red arrows indicate effects of RAR agonists on mediators of Wnt signalling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Determining the Role of Sost and Sostdc1 During Fracture Healing

The bone is a dynamic organ, often changing throughout the course of the human lifespan with its continuous remodeling, laying down new bone and resorbing old bone. With age, the bone becomes increasingly porous and mechanically unstable, leading to the development of osteoporosis in some individuals. Elderly patients with osteoporosis are at an increased risk of fracturing their bones which contributes to a higher mortality rate. Recent studies have revealed that type 1 diabetic mellitus (T1DM) patients also have an osteoporotic bone phenotype and impaired fracture healing, independent of age. Currently, there is a lack of available treatments that can improve impaired healing and directly enhance bone formation. Therefore, there is a great need for developing new therapies that can not only aid type 1 diabetic patients with osteoporosis to improve bone phenotype, but that could also aid patients with difficult or impaired fracture healing. In this thesis, I will be discussing the role of Wnt signaling and Sclerostin, a Wnt antagonist that negatively regulates bone formation, in the content of fracture repair.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

The effect of loading direction on the fracture behaviors of cortical bone at a dynamic loading rate

Here, the dynamic cracking processes in porcine cortical bone were visualized in real-time using the high-speed synchrotron X-ray phase-contrast imaging (PCI) technique in three osteon orientations: in-plane transverse, out-of-plane transverse and in-plane longitudinal. The dynamic flexural loading applied on the pre-notched bone specimens was introduced by a modified Kolsky compression bar. High-speed X-ray images of the entire loading events were documented with a high-speed camera. Three-dimensional X-ray micro-computed tomography was conducted to examine the intact microstructures and obtain the basic material properties of the bone material used for mechanical characterizations. The onset location, where crack initiated, and the subsequent direction, along which the incipient crack propagated, were measured quantitatively using the high-speed X-ray images and the latter was found dependent on the osteon direction significantly. The crack propagation velocities were dependent on crack extension over the entire crack path significantly for all the three directions while the initial velocity for in-plane longitudinal direction was lower than the other two directions. Straight-through crack paths were observed for in-plane longitudinal specimens while the cracks were deflected and twisted in the in-plane transverse direction. For out-of-plane transverse direction, the cracks follow paths with tortuosity fall in between the other two directions, showing a mixed mode of fractures of the former two extreme cases. The toughening mechanisms, visualized by the high-speed X-ray images, and the corresponding fracture toughness, evaluated in terms of fracture initiation toughness and crack growth resistance curve (R-curve), were also found significantly different among the three osteon directions, suggesting an overall transition from brittle to ductile-like fracture behaviors at the dynamic displacement rate (5.4 m/s) as the osteon orientation varies from in-plane longitudinal to out-of-plane transverse, and to in-plane transverse eventually.

42 ENGINEERING↗
NASA NTRS1991

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.↗
DOE OSTI2024

Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity

Skeletal fracture resistance emerges from multiple components of bone structure like microarchitecture, matrix mineralization, and organization. These characteristics are engendered via mechanisms like the hypoxia-inducible factors (HIF) pathway, involving two paralogs, HIF-1α and HIF-2α. Under normoxia, HIF-α is targeted for degradation via von-Hippel Lindau (VHL); hypoxia enables HIF-α stabilization and induction of target genes. We previously showed that osteocytic Vhl deletion or expression of degradation-resistant HIF-2α cDR female mice each produced high bone mass, whereas degradation-resistant osteocytic HIF-1α produced no overt phenotype. We report within that Vhl cKO increased bone strength, while HIF-2α cDR displayed markedly reduced bone strength below Cre-negative controls. This suggests that VHL and HIF-2α drive distinct responses that promote disparate effects on bone strength. Both Vhl deletion or HIF-2α accumulation generated two discrete bone morphologies: an outer lamellar cortex and a woven, poorly mineralized endocortex that imparted dramatically different functional outcomes. Our studies reveal novel influence of osteocytic HIF-2α signaling on collagen matrix organization, mineralization, and bone strength.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2010

Male Astronauts Have Greater Bone Loss and Risk of Hip Fracture Following Long Duration Spaceflights than Females

This slide presentation reviews bone loss in males and compares it to female bone loss during long duration spaceflight. The study indicates that males suffer greater bone loss than females and have a greater risk of hip fracture. Two possible reason for the greater male bone loss are that the pre-menopausal females have the estrogen protection and the greater strength of men max out the exercise equipment that provide a limited resistance to 135 kg.

Ellman, Rachel↗
NASA NTRS2018

Effect of Ex Vivo Ionizing Radiation on Static and Fatigue Properties of Mouse Vertebral Bodies

For a variety of medical and scientific reasons, human bones can be exposed to a wide range of ionizing radiation levels. In vivo radiation therapy (0.05 kGy) is used in cancer treatment, and ex vivo irradiation (25-35 kGy) is used to sterilize bone allografts. Ionizing radiation in these applications has been shown to increase risk of fracture, decrease bone quality and degrade collagen integrity. Past studies have investigated the deleterious effects of radiation on cortical or trabecular bone specimens individually, but to date no studies have examined whole bones containing both cortical and trabecular tissue. Furthermore, a clear relationship between the dose and the mechanical and biochemical response of bone's extracellular matrix has yet to be established for doses ranging from cancer therapy to allograft sterilization (0.05-35 kGy). To gain insight into these issues, we conducted an ex vivo radiation study to investigate non-cellular (i.e. matrix) effects of ionizing radiation dose on vertebral whole bone mechanical properties, over a range of radiation doses (0.05-35 kGy), with a focus on any radiation-induced changes in collagen. With underlying mechanisms of action in mind, we hypothesized that any induced reductions in mechanical properties would be associated with changes in collagen integrity. METHODS: 20-week old female mice were euthanized and the lumbar spine was dissected using IACUC approved protocols. The lumbar vertebrae (L1- S1) were extracted from the spine via cuts through adjacent intervertebral discs, and the endplates, posterior processes, surrounding musculature, and soft tissues were removed (approx. 1.5mm diameter, approx. 2mm height). Specimens were randomly assigned to one of five groups for ex vivo radiation exposure: x-ray irradiation at 0.05, 1, 17, or 35 kGy, or a 0 kGy control. Following irradiation, the vertebrae were imaged using microcomputed tomography (micro-CT) and then subjected to either monotonic compressive loading to failure or uniform cyclic compressive loading. During cyclic testing, samples were loaded in force control to a force level that corresponded to a strain of 0.46%, as determined in advance by a linearly elastic micro-CT-based finite element analysis for each specimen. Tests were stopped at imminent fracture, defined as a rapid increase in strain. The main outcome for the monotonic test was the strength (maximum force); for cyclic testing it was the fatigue life (log of the number of cycles of loading at imminent failure). A fluorometric assay was used on the S1 vertebrae to measure the number of non-enzymatic collagen crosslinks[4]. A one-way ANOVA was performed on mechanical properties and collagen crosslinks; means were compared with controls using Dunnett's method, with a Tukey-Kramer post-hoc analysis when significance was found (p < or = 0.05). RESULTS: Compared to the unirradiated control group, the concentration of non-enzymatic collagen crosslinks was significantly increased for all irradiated groups (p < 0.0001), and being higher by at least 50% (Figure 1a). By contrast, the radiation effects on the collagen were only evident at the higher doses. For irradiation exposures of 17 kGy or more, strength decreased substantially as the radiation level was increased, but no effect was evident below 17 kGy (Figure 1b). There was no significant change in the stiffness or maximum displacement for any radiation dose (p>0.05). The finite element analysis prescribed force level for cyclic loading exceeded the measured (monotonic) strength of the 17 and 35 kGy irradiated groups (mean +/- SD, 20.6 +/- 5.6 N; 13.2 +/- 3.7 N, respectively) and therefore these groups were eliminated from the fatigue study. The fatigue life for the 0.05 and 1 kGy groups were similar to each other and were not statistically significantly different from the control group (Figure 1c).

radiation↗
DOE OSTI2016

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH){sub 2} vitamin D{sub 3} (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast apoptosis by cAMP-induced ROS generation. • Theophylline levels in bone marrow were much higher than blood. • Theophylline diminished bone regeneration at the fracture site and caused osteopenia. • Theophylline caused hypo-vitaminosis D, and altered calciotropic hormones. • Vitamin D treatment prevented theophylline-induced changes in bone metabolism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Influence of physical activity on tibial bone material properties in laying hens

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as cortical and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Efficacy of the Vertebral Body Stenting System for the Restoration of Vertebral Height in Acute Traumatic Compression Fractures in a Non-osteoporotic Population

Introduction: To evaluate the effectiveness of percutaneous image-guided vertebral body stenting (VBS) at restoring vertebral height in acute, stable, traumatic thoracolumbar fractures in a young, non-osteoporotic population. Materials and Methods: A single-centre retrospective review of all traumatic non-osteoporotic fractures treated with VBS between 2010 and 2017 was performed. Inclusion criteria included patients with recent (< 10 days), symptomatic and stable thoracolumbar compression fractures. Patients with low-energy fractures, osteoporosis and age > 60/50 years (male/female) were excluded. Primary outcomes included: correction of vertebral height, correction of kyphosis angle and Beck Index on reconstructed pre- and post-procedural CBCT images. Secondary outcomes included intra-procedural stent recoil, complications, cement leakage and factors predicting height restoration. Results: Thirty-nine patients (26 men, 13 women; mean age 33.6 years, range 15–57 years) underwent VBS 5 days post-trauma on average (range 1–10), for stable compression fractures located between T5 and L5. Mean vertebral height gain, vertebral kyphosis angle correction and Beck index improvement were 3.8 mm (95% CI 3.36–4.50; P(> 3 mm) = 99.9%), 4.3° (95% CI 3.50–5.20; P(> 3°) = 99.9%) and 0.07 [95% CI 0.053–0.11], respectively (all statistically significant). Technical success was 92%, with 3 “major” stent recoils resulting in loss of vertebral height correction. No symptomatic complications were observed. No predictive factors for procedural success were identified. Conclusion: VBS can significantly restore vertebral height in young patients with traumatic vertebral compression fractures.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Nondestructive geochemical characterization of fossil hominin taphonomy and burial history

To date, only three Homo habilis specimens have been discovered that have associated craniodental and postcranial elements, providing a limited fossil record of the ontogeny and morphology of early members of the genus Homo. Recently, a nearly complete dentition, likely attributable to H. habilis, was discovered and excavated from early Pleistocene-age fluvial-lacustrine sediments of the upper Burgi Member of the Koobi Fora Formation at site F25787 in Area 13, near Ileret, Kenya. On the surface less than 15 m away, at site F25966, postcranial elements were found, which, if from the same individual as the nearby dentition, would represent the fourth associated craniodental and postcranial assemblage of this species. We developed a geochemical taphonomic history of these ca. 2 Ma hominin fossils using nondestructive X-ray based microanalytical tools (synchrotron and benchtop X-ray fluorescence chemical imaging and micro- and nano-computed tomography volumetric reconstruction), bulk analyses of sediments and paleosols at the excavation sites, and sedimentologic and stratigraphic observations. We integrate the chemical and physical taphonomic histories to test whether teeth (excavated in situ) and postcranial bones (eroded onto the outcrop surface) derive from a single individual. Minor differences in taphonomic history are attributable to the different biomineral properties of the dental and osseous components and to differences in physical damage during early post-mortem scavenging, dispersal, and burial in adjacent depositional settings. Microscale geochemical mapping enabled the temporal ordination of chemical and physical events in the specimens’ chemical taphonomic histories. Specifically, authigenic Fe- and K-bearing clays and Y, U, and Sr uptake occurred in post-burial fractures in bones and were also incorporated pervasively throughout dentin in teeth. Barite mineralization occurred along the latest fractures in both materials, and as a coating on tooth roots. The stratigraphic, taphonomic, and geochemical evidence supports the interpretation that the hominin fossils represent a single individual. Finally, successful application of these nondestructive sample characterization methods demonstrates capabilities for thorough interrogation of the taphonomic histories of other potential hominin fossil associations, enabling more robust and accurate palaeontologic constraints using those relationships.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Vertebral Augmentation with Nitinol Endoprosthesis: Clinical Experience in 40 Patients with 1-Year Follow-up

Purpose: This study was designed to assess the clinical outcomes of patients treated by vertebral augmentation with nitinol endoprosthesis (VNE) to treat painful vertebral compression fractures. Methods: Forty patients with one or more painful osteoporotic VCF, confirmed by MRI and accompanied by back-pain unresponsive to a minimum 2 months of conservative medical treatment, underwent VNE at 42 levels. Preoperative and postoperative pain measured with Visual Analog Scale (VAS), disability measured by Oswestry Disability Index (ODI), and vertebral height restoration (measured with 2-dimensional reconstruction CT) were compared at last follow-up (average follow-up 15 months). Cement extravasation, subsequent fractures, and implant migration were recorded. Results: Long-term follow-up was obtained in 38 of 40 patients. Both VAS and ODI significantly improved from a median of 8.0 (range 5–10) and 66 % (range 44–88 %) to 0.5 (range 0–8) and 6 % (range 6–66 %), respectively, at 1 year (p < 0.0001). Vertebral height measurements comparing time points increased in a statistically significant manner (ANOVA, p < 0.001). Overall cement extravasation rate was 9.5 %. Discal and venous leakage rates were 7.1 and 0 % respectively. No symptomatic extravasations occurred. Five of 38 (13.1 %) patients experienced new spontaneous, osteoporotic fractures. No device change or migration was observed. Conclusions: VNE is a safe and effective procedure that is able to provide long-lasting pain relief and durable vertebral height gain with a low rate of new fractures and cement leakages.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture

PurposeTo retrospectively evaluate the effectiveness of computed tomography-guided percutaneous microwave ablation (MWA) and cementoplasty in patients with painful bone metastases at high risk of fracture.Materials and MethodsThirty-five patients with 37 metastatic bone lesions underwent computed tomography-guided MWA combined with cementoplasty (polymethylmethacrylate injection). Vertebrae, femur, and acetabulum were the intervention sites and the primary end point was pain relief. Pain severity was estimated by visual analog scale (VAS) before treatment; 1 week post-treatment; and 1, 6, and 12 months post-treatment. Functional outcome was assessed by improved patient walking ability. Radiological evaluation was performed at baseline and 3 and 12 months post-procedure.ResultsIn all patients, pain reduction occurred from the first week after treatment. The mean reduction in the VAS score was 84, 90, 90 % at week 1, month 1, and month 6, respectively. Improved walking ability occurred in 100 and 98 % of cases at the 1- and 6-month functional outcome evaluations, respectively. At the 1-year evaluation, 25 patients were alive, and 10 patients (28 %) had died because of widespread disease. The mean reduction in the VAS score and improvement in surviving patients’ walking ability were 90 and 100 %, respectively. No patients showed evidence of local tumor recurrence or progression and pathological fracture in the treated sites.ConclusionOur results suggest that MWA combined with osteoplasty is safe and effective when treating painful bone metastases at high risk of fracture. The number of surviving patients at the 1-year evaluation confirms the need for an effective and long-lasting treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Role of Assay Type in Determining Free 25-Hydroxyvitamin D Levels in Diverse Populations

Serum 25-hydroxyvitamin D (25OHD) is the most frequently used marker of vitamin D status. Low 25OHD is associated with bone loss, fractures {Cauley, 2010 #1516;Ensrud, 2009 #1517}, and other adverse health outcomes {Theodoratou, 2014 #1518}. Most extra renal tissues only have access to free 25OHD, and free 25OHD concentration is thus a plausible biomarker of 25OHD availability and function {Johnsen, 2014 #1443;Chun, 2014 #1343}. Stronger associations with free or bioavailable 25OHD than with total 25OHD were reported for serum calcium, parathyroid hormone (PTH) {Bhan, 2012 #1124} and bone mineral density (BMD) {Powe, 2011 #1129}. These findings have led to the suggestion that free or bioavailable 25OHD may provide a more clinically relevant measure of tissue 25OHD availability and vitamin D status {Powe, 2013 #1369; Holick NEJM 2013 editorial}. The US Preventive Services Task Force (LeFevre 2015) recently pointed to the gap in research regarding bioavailable and free 25OHD and noted the possibility that these may be better markers of tissue 25OHD availability. Free 25OHD is conventionally calculated from the concentrations of total 25OHD, vitamin D binding protein (DBP) and albumin, with or without a factor accounting for DBP genotype-specific binding affinities {Bouillon, 1981 #1207;Chun, 2012 #1143; Powe, 2011 #1129;Johnsen, 2014 #1443}. DBP—or Group specific component (GC) {Hirschfeld, 1959 #1468}—polymorphisms (rs4588 and rs7041) give rise to three major polymorphic isoforms of DBP, GC-1F, GC-1S and GC-2, the frequencies of which differ globally, with GC-1F alleles more common in populations of African descent {Kambou, 1986 #1122}. Although DBP is a primary component of free and bioavailable 25OHD calculations, substantial variation in DBP between assays has been noted (Powe suggest to cite here previous publications as in previous version of this Ms). Using DBP measured by a monoclonal antibody Powe et al. {Powe, 2013 #1369} concluded that calculated free 25OHD in African-Americans was equal or higher than in US whites, questioning the implications of low total 25OHD concentrations in African Americans (Holick 2013). This idea gained widespread attention in medical and lay press {LeFevre, 2015 #1598; Bhan, 2014 #1485; Durazo-Arvizu, 2014 #1519}, and many others) and may have important implications for nutrional supplementation policy. To better understand the importance of free 25OHD estimates, and its racial differences, we conducted studies in cohorts based in the US, UK and The Gambia that included participants of African and European ancestry known to differ in GC genotype distribution. We characterized the molecular forms of circulating DBP through comparison of several DBP assays and DBP peptide proteomic analysis, to obtain both calculated and directly measured free 25OHD by geographical region, race and GC genotype.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2016

The Value of Rotational Venography Versus Anterior–Posterior Venography in 100 Consecutive IVC Filter Retrievals

PurposeAccurately detecting inferior vena cava (IVC) filter complications is important for safe and successful retrieval as tip-embedded filters require removal with non-standard techniques. Venography prior to IVC filter retrieval has traditionally used a single anterior–posterior (AP) projection. This study compares the utility of rotational venography to AP venography prior to IVC filter removal.Materials and MethodsThe rotational venograms from 100 consecutive IVC filter retrievals over a 35-month period were evaluated retrospectively. The AP view of the rotational venogram was examined separately from the full series by a radiologist blinded to alternative imaging and operative findings. The venograms were evaluated for tip embedding, filter fracture, filter thrombus, and IVC thrombus. Statistical analysis was performed.ResultsUsing operative findings and peri-procedural imaging as the reference standard, tip embedding occurred in 59 of the 100 filters (59 %). AP venography was used to correctly identify 31 tip-embedded filters (53 % sensitivity) with two false positives (95 % specificity) for an accuracy of 70 %. Rotational venography was used to correctly identify 58 tip-embedded filters (98 % sensitivity) with one false positive (98 % specificity) for an accuracy of 98 %. A significant difference was found in the sensitivities of the two diagnostic approaches (P < .01). Other findings of thrombus and filter fracture were not significantly different between the two groups.ConclusionRotational venograms allow for more accurate detection of tip-embedded IVC filters compared to AP views alone. As this determines the approach taken, rotational venograms are helpful if obtained prior to IVC filter retrieval.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Endovascular Management of Infected Femoral Artery Pseudoaneurysms in High-Risk Patients: A Case Series

We report our experience with the urgent treatment of two high-risk patients with infected femoral artery pseudoaneurysms (IFAPs) with the placement of a self-expandable covered stent (SECS). In both cases, there was no perioperative mortality and the aneurysm exclusion was successful without early or late stent thrombosis/stent fracture nor acute or chronic limb ischemia or limb loss. There was no recurrence of local or systemic infection during the follow-up period. Endovascular therapy represents a feasible treatment option for IFAPs in those patients for whom the risk of open surgical repair would be prohibitive, especially under urgent circumstances.

62 RADIOLOGY AND NUCLEAR MEDICINE↗