Effects of Scan Resolutions and Element Sizes on Bovine Vertebral Mechanical Parameters from Quantitative Computed Tomography-Based Finite Element Analysis

PubMed Central

Zhang, Meng; Gao, Jiazi; Huang, Xu; Zhang, Min; Liu, Bei

2017-01-01

Quantitative computed tomography-based finite element analysis (QCT/FEA) has been developed to predict vertebral strength. However, QCT/FEA models may be different with scan resolutions and element sizes. The aim of this study was to explore the effects of scan resolutions and element sizes on QCT/FEA outcomes. Nine bovine vertebral bodies were scanned using the clinical CT scanner and reconstructed from datasets with the two-slice thickness, that is, 0.6 mm (PA resolution) and 1 mm (PB resolution). There were significantly linear correlations between the predicted and measured principal strains (R2 > 0.7, P < 0.0001), and the predicted vertebral strength and stiffness were modestly correlated with the experimental values (R2 > 0.6, P < 0.05). Two different resolutions and six different element sizes were combined in pairs, and finite element (FE) models of bovine vertebral cancellous bones in the 12 cases were obtained. It showed that the mechanical parameters of FE models with the PB resolution were similar to those with the PA resolution. The computational accuracy of FE models with the element sizes of 0.41 × 0.41 × 0.6 mm3 and 0.41 × 0.41 × 1 mm3 was higher by comparing the apparent elastic modulus and yield strength. Therefore, scan resolution and element size should be chosen optimally to improve the accuracy of QCT/FEA. PMID:29065624

Standardizing evaluation of pQCT image quality in the presence of subject movement: qualitative versus quantitative assessment.

PubMed

Blew, Robert M; Lee, Vinson R; Farr, Joshua N; Schiferl, Daniel J; Going, Scott B

2014-02-01

Peripheral quantitative computed tomography (pQCT) is an essential tool for assessing bone parameters of the limbs, but subject movement and its impact on image quality remains a challenge to manage. The current approach to determine image viability is by visual inspection, but pQCT lacks a quantitative evaluation. Therefore, the aims of this study were to (1) examine the reliability of a qualitative visual inspection scale and (2) establish a quantitative motion assessment methodology. Scans were performed on 506 healthy girls (9-13 years) at diaphyseal regions of the femur and tibia. Scans were rated for movement independently by three technicians using a linear, nominal scale. Quantitatively, a ratio of movement to limb size (%Move) provided a measure of movement artifact. A repeat-scan subsample (n = 46) was examined to determine %Move's impact on bone parameters. Agreement between measurers was strong (intraclass correlation coefficient = 0.732 for tibia, 0.812 for femur), but greater variability was observed in scans rated 3 or 4, the delineation between repeat and no repeat. The quantitative approach found ≥95% of subjects had %Move <25 %. Comparison of initial and repeat scans by groups above and below 25% initial movement showed significant differences in the >25 % grouping. A pQCT visual inspection scale can be a reliable metric of image quality, but technicians may periodically mischaracterize subject motion. The presented quantitative methodology yields more consistent movement assessment and could unify procedure across laboratories. Data suggest a delineation of 25% movement for determining whether a diaphyseal scan is viable or requires repeat.

Standardizing Evaluation of pQCT Image Quality in the Presence of Subject Movement: Qualitative vs. Quantitative Assessment

PubMed Central

Blew, Robert M.; Lee, Vinson R.; Farr, Joshua N.; Schiferl, Daniel J.; Going, Scott B.

2013-01-01

Purpose Peripheral quantitative computed tomography (pQCT) is an essential tool for assessing bone parameters of the limbs, but subject movement and its impact on image quality remains a challenge to manage. The current approach to determine image viability is by visual inspection, but pQCT lacks a quantitative evaluation. Therefore, the aims of this study were to (1) examine the reliability of a qualitative visual inspection scale, and (2) establish a quantitative motion assessment methodology. Methods Scans were performed on 506 healthy girls (9–13yr) at diaphyseal regions of the femur and tibia. Scans were rated for movement independently by three technicians using a linear, nominal scale. Quantitatively, a ratio of movement to limb size (%Move) provided a measure of movement artifact. A repeat-scan subsample (n=46) was examined to determine %Move’s impact on bone parameters. Results Agreement between measurers was strong (ICC = .732 for tibia, .812 for femur), but greater variability was observed in scans rated 3 or 4, the delineation between repeat or no repeat. The quantitative approach found ≥95% of subjects had %Move <25%. Comparison of initial and repeat scans by groups above and below 25% initial movement, showed significant differences in the >25% grouping. Conclusions A pQCT visual inspection scale can be a reliable metric of image quality but technicians may periodically mischaracterize subject motion. The presented quantitative methodology yields more consistent movement assessment and could unify procedure across laboratories. Data suggest a delineation of 25% movement for determining whether a diaphyseal scan is viable or requires repeat. PMID:24077875

Clinical Imaging of Bone Microarchitecture with HR-pQCT

PubMed Central

Nishiyama, Kyle K.; Shane, Elizabeth

2014-01-01

Osteoporosis, a disease characterized by loss of bone mass and structural deterioration, is currently diagnosed by dual-energy x-ray absorptiometry (DXA). However, DXA does not provide information about bone microstructure, which is a key determinant of bone strength. Recent advances in imaging permit the assessment of bone microstructure in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT). From these data, novel image processing techniques can be applied to characterize bone quality and strength. To date, most HR-pQCT studies are cross-sectional comparing subjects with and without fracture. These studies have shown that HR-pQCT is capable of discriminating fracture status independent of DXA. Recent longitudinal studies present new challenges in terms of analyzing the same region of interest and multisite calibrations. Careful application of analysis techniques and educated clinical interpretation of HR-pQCT results have improved our understanding of various bone-related diseases and will no doubt continue to do so in the future. PMID:23504496

Application of high resolution pQCT analysis for the assessment of a bone lesion: a technical note.

PubMed

Rubinacci, A; Tresoldi, D; Villa, I; Rizzo, G; Gaudio, D; De Angelis, D; Gibelli, D; Cattaneo, C

2015-01-01

Peripheral quantitative computed tomography (pQCT) has found new fields of application in bone medicine, but none of them concerns the forensic practice. This study exposes the potential of pQCT applied to a penetrating lesion in a vertebral body. A pQCT scanner was used for the measurements (XCT Research SA+; Stratec Medizintechnik GmbH, Pforzheim, Germany). A more precise reconstruction of the path of the lesion within the trabecular bone was reached, with more details concerning the morphological characteristics of the lesion inside the vertebral body, and the elaboration of a 3D model was created, which allowed the operator to define the volume of the lack of tissues related to the lesion. The application of pQCT scan proved to be a potentially useful tool for the assessment of bone lesions, although further studies are needed in order to verify its applicability to forensic context. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. Themore » methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm{sup 3} corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.« less

Clinical cone beam computed tomography compared to high-resolution peripheral computed tomography in the assessment of distal radius bone.

PubMed

de Charry, C; Boutroy, S; Ellouz, R; Duboeuf, F; Chapurlat, R; Follet, H; Pialat, J B

2016-10-01

Clinical cone beam computed tomography (CBCT) was compared to high-resolution peripheral quantitative computed tomography (HR-pQCT) for the assessment of ex vivo radii. Strong correlations were found for geometry, volumetric density, and trabecular structure. Using CBCT, bone architecture assessment was feasible but compared to HR-pQCT, trabecular parameters were overestimated whereas cortical ones were underestimated. HR-pQCT is the most widely used technique to assess bone microarchitecture in vivo. Yet, this technology has been only applicable at peripheral sites, in only few research centers. Clinical CBCT is more widely available but quantitative assessment of the bone structure is usually not performed. We aimed to compare the assessment of bone structure with CBCT (NewTom 5G, QR, Verona, Italy) and HR-pQCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland). Twenty-four distal radius specimens were scanned with these two devices with a reconstructed voxel size of 75 μm for Newtom 5G and 82 μm for XtremeCT, respectively. A rescaling-registration scheme was used to define the common volume of interest. Cortical and trabecular compartments were separated using a semiautomated double contouring method. Density and microstructure were assessed with the HR-pQCT software on both modality images. Strong correlations were found for geometry parameters (r = 0.98-0.99), volumetric density (r = 0.91-0.99), and trabecular structure (r = 0.94-0.99), all p < 0.001. Correlations were lower for cortical microstructure (r = 0.80-0.89), p < 0.001. However, absolute differences were observed between modalities for all parameters, with an overestimation of the trabecular structure (trabecular number, 1.62 ± 0.37 vs. 1.47 ± 0.36 mm(-1)) and an underestimation of the cortical microstructure (cortical porosity, 3.3 ± 1.3 vs. 4.4 ± 1.4 %) assessed on CBCT images compared to HR-pQCT images. Clinical CBCT devices are able to analyze large portions of distal bones with good spatial resolution and limited irradiation. However, compared to dedicated HR-pQCT, the assessment of microarchitecture by NewTom 5G dental CBCT showed some discrepancies, for density measurements mainly. Further technical developments are required to reach optimal assessment of bone characteristics.

High Resolution Peripheral Quantitative Computed Tomography for Assessment of Bone Quality

NASA Astrophysics Data System (ADS)

Kazakia, Galateia

2014-03-01

The study of bone quality is motivated by the high morbidity, mortality, and societal cost of skeletal fractures. Over 10 million people are diagnosed with osteoporosis in the US alone, suffering 1.5 million osteoporotic fractures and costing the health care system over 17 billion annually. Accurate assessment of fracture risk is necessary to ensure that pharmacological and other interventions are appropriately administered. Currently, areal bone mineral density (aBMD) based on 2D dual-energy X-ray absorptiometry (DXA) is used to determine osteoporotic status and predict fracture risk. Though aBMD is a significant predictor of fracture risk, it does not completely explain bone strength or fracture incidence. The major limitation of aBMD is the lack of 3D information, which is necessary to distinguish between cortical and trabecular bone and to quantify bone geometry and microarchitecture. High resolution peripheral quantitative computed tomography (HR-pQCT) enables in vivo assessment of volumetric BMD within specific bone compartments as well as quantification of geometric and microarchitectural measures of bone quality. HR-pQCT studies have documented that trabecular bone microstructure alterations are associated with fracture risk independent of aBMD.... Cortical bone microstructure - specifically porosity - is a major determinant of strength, stiffness, and fracture toughness of cortical tissue and may further explain the aBMD-independent effect of age on bone fragility and fracture risk. The application of finite element analysis (FEA) to HR-pQCT data permits estimation of patient-specific bone strength, shown to be associated with fracture incidence independent of aBMD. This talk will describe the HR-pQCT scanner, established metrics of bone quality derived from HR-pQCT data, and novel analyses of bone quality currently in development. Cross-sectional and longitudinal HR-pQCT studies investigating the impact of aging, disease, injury, gender, race, and therapeutics on bone quality will be discussed.

Advances in Imaging Approaches to Fracture Risk Evaluation

PubMed Central

Manhard, Mary Kate; Nyman, Jeffry S.; Does, Mark D.

2016-01-01

Fragility fractures are a growing problem worldwide, and current methods for diagnosing osteoporosis do not always identify individuals who require treatment to prevent a fracture and may misidentify those not a risk. Traditionally, fracture risk is assessed using dual-energy X-ray absorptiometry, which provides measurements of areal bone mineral density (BMD) at sites prone to fracture. Recent advances in imaging show promise in adding new information that could improve the prediction of fracture risk in the clinic. As reviewed herein, advances in quantitative computed tomography (QCT) predict hip and vertebral body strength; high resolution HR-peripheral QCT (HR-pQCT) and micro-magnetic resonance imaging (μMRI) assess the micro-architecture of trabecular bone; quantitative ultrasound (QUS) measures the modulus or tissue stiffness of cortical bone; and quantitative ultra-short echo time MRI methods quantify the concentrations of bound water and pore water in cortical bone, which reflect a variety of mechanical properties of bone. Each of these technologies provides unique characteristics of bone and may improve fracture risk diagnoses and reduce prevalence of fractures by helping to guide treatment decisions. PMID:27816505

Bone strength measured by peripheral quantitative computed tomography and the risk of nonvertebral fractures: the osteoporotic fractures in men (MrOS) study.

PubMed

Sheu, Yahtyng; Zmuda, Joseph M; Boudreau, Robert M; Petit, Moira A; Ensrud, Kristine E; Bauer, Douglas C; Gordon, Christopher L; Orwoll, Eric S; Cauley, Jane A

2011-01-01

Many fractures occur in individuals without osteoporosis defined by areal bone mineral density (aBMD). Inclusion of other aspects of skeletal strength may be useful in identifying at-risk subjects. We used surrogate measures of bone strength at the radius and tibia measured by peripheral quantitative computed tomography (pQCT) to evaluate their relationships with nonvertebral fracture risk. Femoral neck (FN) aBMD, measured by dual-energy X-ray absorptiometry (DXA), also was included. The study population consisted of 1143 white men aged 69+ years with pQCT measures at the radius and tibia from the Minneapolis and Pittsburgh centers of the Osteoporotic Fractures in Men (MrOS) study. Principal-components analysis and Cox proportional-hazards modeling were used to identify 21 of 58 pQCT variables with a major contribution to nonvertebral incident fractures. After a mean 2.9 years of follow-up, 39 fractures occurred. Men without incident fractures had significantly greater bone mineral content, cross-sectional area, and indices of bone strength than those with fractures by pQCT. Every SD decrease in the 18 of 21 pQCT parameters was significantly associated with increased fracture risk (hazard ration ranged from 1.4 to 2.2) independent of age, study site, body mass index (BMI), and FN aBMD. Using area under the receiver operation characteristics curve (AUC), the combination of FN aBMD and three radius strength parameters individually increased fracture prediction over FN aBMD alone (AUC increased from 0.73 to 0.80). Peripheral bone strength measures are associated with fracture risk and may improve our ability to identify older men at high risk of fracture. © 2011 American Society for Bone and Mineral Research.

Effect of Exercise and Antidepressants on Skeletal Outcomes in Adolescent Girls With Anorexia Nervosa.

PubMed

DiVasta, Amy D; Feldman, Henry A; O'Donnell, Jennifer M; Long, Jin; Leonard, Mary B; Gordon, Catherine M

2017-02-01

We examined the relationships between malnutrition, lifestyle factors, and bone health in anorexia nervosa (AN) via dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Seventy adolescent girls with AN and 132 normal-weighted controls underwent pQCT tibial measures including trabecular volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness. Participants with AN underwent DXA measures of the axial skeleton. We assessed the association of DXA and pQCT measures with clinical and lifestyle variables. Body mass index Z-score and ideal body weight percentage were positively correlated with trabecular vBMD, cortical CSA, and section modulus (p < .04). Exercise was associated with all pQCT measures but only with hip BMD by DXA. In AN, the use of antidepressants was associated with lower pQCT measures (p < .03). Antidepressants may negatively, and exercise positively, influence BMD in adolescents with eating disorders. These findings offer a provocative look at two longstanding questions. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Sex- and Age-Related Differences in Bone Microarchitecture in Men Relative to Women Assessed by High-Resolution Peripheral Quantitative Computed Tomography

PubMed Central

Amin, Shreyasee; Khosla, Sundeep

2012-01-01

The trabecular and cortical compartments of bone each contributes to bone strength. Until recently, assessment of trabecular and cortical microstructure has required a bone biopsy. Now, trabecular and cortical microstructure of peripheral bone sites can be determined noninvasively using high-resolution peripheral quantitative computed tomography (HR-pQCT). Studies that have used HR-pQCT to evaluate cohorts of both men and women have provided novel insights into the changes in bone microarchitecture that occur with age between the sexes, which may help to explain the lower fracture incidence in older men relative to women. This review will highlight observations from these studies on both the sex- and age-related differences in trabecular and cortical microstructure that may underlie the differences in bone strength, and thereby fracture risk, between men and women. PMID:22496983

Improving Bone-Health Monitoring in Astronauts: Recommended Use of Quantitative Computed Tomography [QCT] for Clinical and Operational Decisions by NASA

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Truszkowski, P.

2010-01-01

DXA measurement of areal bone mineral density [aBMD,g/cm2] is required by NASA for assessing skeletal integrity in astronauts. Due to the abundance of population-based data that correlate hip and spine BMDs to fragility fractures, BMD is widely applied as a predictor of fractures in the general aging population. In contrast, QCT is primarily a research technology that measures three-dimensional , volumetric BMD (vBMD,mg/cm3) of bone and is therefore capable of differentiating between cortical and trabecular components. Additionally, when combined with Finite Element Modeling [FEM], a computational tool, QCT data can be used to estimate the whole bone strength of the hip [FE strength] for a specific load vector. A recent report demonstrated that aBMD failed to correlate with incurred changes in FE strength (for fall and stance loading) by astronauts over typical 180-day ISS (International Space Station) missions. While there are no current guidelines for using QCT data in clinical practice, QCT increases the understanding of how bone structure and mineral content are affected by spaceflight and recovery on Earth. In order to understand/promote/consider the use of QCT, NASA convened a panel of clinicians specializing in osteoporosis. After reviewing the available, albeit limited, medical and research information from long-duration astronauts (e.g., data from DXA, QCT, FEM, biochemistry analyses, medical records and in-flight exercise performance) the panelists were charged with recommending how current and future research data and analyses could inform clinical and operational decisions. The Panel recommended that clinical bone tests on astronauts should include QCT (hip and lumbar spine) for occupational risk surveillance and for the estimation of whole hip bone strength as derived by FEM. FE strength will provide an improved index that NASA could use to select astronauts of optimal bone health for extended duration missions, for repeat missions or for specific mission operations.

Childhood Forearm Breaks Resulting from Mild Trauma May Indicate Bone Deficits

MedlinePlus

... a powerful new technology called high-resolution peripheral quantitative computed tomography (HRpQCT), which, unlike DXA, can assess ... persist throughout life. The investigators concluded that additional research is needed to determine if childhood bone weakness ...

Estimation of whole body fat from appendicular soft tissue from peripheral quantitative computed tomography in adolescent girls

PubMed Central

Lee, Vinson R.; Blew, Rob M.; Farr, Josh N.; Tomas, Rita; Lohman, Timothy G.; Going, Scott B.

2013-01-01

Objective Assess the utility of peripheral quantitative computed tomography (pQCT) for estimating whole body fat in adolescent girls. Research Methods and Procedures Our sample included 458 girls (aged 10.7 ± 1.1y, mean BMI = 18.5 ± 3.3 kg/m2) who had DXA scans for whole body percent fat (DXA %Fat). Soft tissue analysis of pQCT scans provided thigh and calf subcutaneous percent fat and thigh and calf muscle density (muscle fat content surrogates). Anthropometric variables included weight, height and BMI. Indices of maturity included age and maturity offset. The total sample was split into validation (VS; n = 304) and cross-validation (CS; n = 154) samples. Linear regression was used to develop prediction equations for estimating DXA %Fat from anthropometric variables and pQCT-derived soft tissue components in VS and the best prediction equation was applied to CS. Results Thigh and calf SFA %Fat were positively correlated with DXA %Fat (r = 0.84 to 0.85; p <0.001) and thigh and calf muscle densities were inversely related to DXA %Fat (r = −0.30 to −0.44; p < 0.001). The best equation for estimating %Fat included thigh and calf SFA %Fat and thigh and calf muscle density (adj. R2 = 0.90; SEE = 2.7%). Bland-Altman analysis in CS showed accurate estimates of percent fat (adj. R2 = 0.89; SEE = 2.7%) with no bias. Discussion Peripheral QCT derived indices of adiposity can be used to accurately estimate whole body percent fat in adolescent girls. PMID:25147482

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Quantitative in vivo HR-pQCT imaging of 3D wrist and metacarpophalangeal joint space width in rheumatoid arthritis.

PubMed

Burghardt, Andrew J; Lee, Chan Hee; Kuo, Daniel; Majumdar, Sharmila; Imboden, John B; Link, Thomas M; Li, Xiaojuan

2013-12-01

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82 μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N = 16, age: 52.6 ± 12.8) and healthy controls (CTRL, N = 7, age: 50.1 ± 15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD)-a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater vs. CTRL (p < 0.01), and JSW.MIN was more than two-fold lower (p < 0.001). Similarly, JSW.SD was significantly greater in the wrist of RA patients vs. CTRL (p < 0.05). In vivo precision was highest for JSW (SDD: 100 μm, RMSCV: 2.1%) while the SDD for JSW.MIN and JSW.SD were 370 and 110 μm, respectively. This study suggests that in vivo quantification of 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases.

Quantitative In Vivo HR-pQCT Imaging of 3D Wrist and Metacarpophalangeal Joint Space Width In Rheumatoid Arthritis

PubMed Central

Burghardt, Andrew J.; Lee, Chan Hee; Kuo, Daniel; Majumdar, Sharmila; Imboden, John B.; Link, Thomas M.; Li, Xiaojuan

2013-01-01

In this technique development study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to non-invasively image and quantify 3D joint space morphology of the wrist and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA). HR-pQCT imaging (82μm voxel-size) of the dominant hand was performed in patients with diagnosed rheumatoid arthritis (RA, N=16, age:52.6±12.8) and healthy controls (CTRL, N=7, age:50.1±15.0). An automated computer algorithm was developed to segment wrist and MCP joint spaces. The 3D distance transformation method was applied to spatially map joint space width, and summarized by the mean joint space width (JSW), minimal and maximal JSW (JSW.MIN, JSW.MAX), asymmetry (JSW.AS), and distribution (JSW.SD) – a measure of joint space heterogeneity. In vivo precision was determined for each measure by calculating the smallest detectable difference (SDD) and root mean square coefficient of variation (RMSCV%) of repeat scans. Qualitatively, HR-pQCT images and pseudo-color JSW maps showed global joint space narrowing, as well as regional and focal abnormalities in RA patients. In patients with radiographic JSN at an MCP, JSW.SD was two-fold greater versus CTRL (p<0.01), and JSW.MIN was more than two-fold lower (p<0.001). Similarly, JSW.SD was significantly greater in the wrist of RA patients versus CTRL (p<0.05). In vivo precision was highest for JSW (SDD: 100μm, RMSCV: 2.1%) while the SDD for JSW.MIN and JSW.SD were 370 and 110μm, respectively. This study suggests that in vivo quantification of 3D joint space morphology from HR-pQCT, could improve early detection of joint damage in rheumatological diseases. PMID:23887879

Preliminary studies of mineralization during distraction osteogenesis.

PubMed

Aronson, J; Good, B; Stewart, C; Harrison, B; Harp, J

1990-01-01

Distraction osteogenesis by the Ilizarov method was performed on 20 dogs. Mineralization at the site of the left tibial metaphyseal lengthening was measured by weekly quantitative computer tomography (QCT) using the contralateral tibia as a control. Four dogs each were killed on Days 7, 14, 21, and 28 of distraction in order to correlate QCT with microradiology, nondecalcified histology, quantitative calcium analysis, and scanning electron microscopy. It was consistently found that intramembranous ossification proceeded centripetally from each corticotomy surface toward the central fibrous interzone. Bone columns crystallized along longitudinally oriented collagen bundles, expanding circumferentially to surrounding bundles. As the distraction gap increased, the bone columns increased in length and in diameter, while the fibrous interzone remained about 4 mm long. Histologically, the bone columns resembled stalagmites and stalactites, as seen by microradiography and scanning electron microscopy, that projected from each corticotomy surface toward the center. These cones reached maximum diameters of 150-200 mu at the corticotomy surfaces. Radiodensity (QCT) increased gradually from the central fibrous interzone toward each corticotomy surface. Mineral density, as determined by calcium quantification, reflected the microscopic geometry and radiographic polarity.

[Imaging of diabetic osteopathy].

PubMed

Patsch, J; Pietschmann, P; Schueller-Weidekamm, C

2015-04-01

Diabetic bone diseases are more than just osteoporosis in patients with diabetes mellitus (DM): a relatively high bone mineral density is paired with a paradoxically high risk of fragility fractures. Diabetics exhibit low bone turnover, osteocyte dysfunction, relative hypoparathyroidism and an accumulation of advanced glycation end products in the bone matrix. Besides typical insufficiency fractures, diabetics show a high risk for peripheral fractures of the lower extremities (e.g. metatarsal fractures). The correct interdisciplinary assessment of fracture risks in patients with DM is therefore a clinical challenge. There are two state of the art imaging methods for the quantification of fracture risks: dual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Radiography, multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are suitable for the detection of insufficiency fractures. Novel research imaging techniques, such as high-resolution peripheral quantitative computed tomography (HR-pQCT) provide non-invasive insights into bone microarchitecture of the peripheral skeleton. Using MR spectroscopy, bone marrow composition can be studied. Both methods have been shown to be capable of discriminating between type 2 diabetic patients with and without prevalent fragility fractures and thus bear the potential of improving the current standard of care. Currently both methods remain limited to clinical research applications. DXA and HR-pQCT are valid tools for the quantification of bone mineral density and assessment of fracture risk in patients with DM, especially if interpreted in the context of clinical risk factors. Radiography, CT and MRI are suitable for the detection of insufficiency fractures.

The measurement of liver fat from single-energy quantitative computed tomography scans

PubMed Central

Cheng, Xiaoguang; Brown, J. Keenan; Guo, Zhe; Zhou, Jun; Wang, Fengzhe; Yang, Liqiang; Wang, Xiaohong; Xu, Li

2017-01-01

Background Studies of soft tissue composition using computed tomography (CT) scans are often semi-quantitative and based on Hounsfield units (HU) measurements that have not been calibrated with a quantitative CT (QCT) phantom. We describe a study to establish the water (H2O) and dipotassium hydrogen phosphate (K2HPO4) basis set equivalent densities of fat and fat-free liver tissue. With this information liver fat can be accurately measured from any abdominal CT scan calibrated with a suitable phantom. Methods Liver fat content was measured by comparing single-energy QCT (SEQCT) HU measurements of the liver with predicted HU values for fat and fat-free liver tissue calculated from their H2O and K2HPO4 equivalent densities and calibration data from a QCT phantom. The equivalent densities of fat were derived from a listing of its constituent fatty acids, and those of fat-free liver tissue from a dual-energy QCT (DEQCT) study performed in 14 healthy Chinese subjects. This information was used to calculate liver fat from abdominal SEQCT scans performed in a further 541 healthy Chinese subjects (mean age 62 years; range, 31–95 years) enrolled in the Prospective Urban Rural Epidemiology (PURE) Study. Results The equivalent densities of fat were 941.75 mg/cm3 H2O and –43.72 mg/cm3 K2HPO4, and for fat-free liver tissue 1,040.13 mg/cm3 H2O and 21.34 mg/cm3 K2HPO4. Liver fat in the 14 subjects in the DEQCT study varied from 0–17.9% [median: 4.5%; interquartile range (IQR): 3.0–7.9%]. Liver fat in the 541 PURE study subjects varied from –0.3–29.9% (median: 4.9%; IQR: 3.4–6.9%). Conclusions We have established H2O and K2HPO4 equivalent densities for fat and fat-free liver tissue that allow a measurement of liver fat to be obtained from any abdominal CT scan acquired with a QCT phantom. Although radiation dose considerations preclude the routine use of QCT to measure liver fat, the method described here facilitates its measurement in patients having CT scans performed for other purposes. Further studies comparing the results with magnetic resonance (MR) measurements of liver fat are required to validate the method as a useful clinical tool. PMID:28811994

Machine Learning Algorithms Utilizing Quantitative CT Features May Predict Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation.

PubMed

Barbosa, Eduardo J Mortani; Lanclus, Maarten; Vos, Wim; Van Holsbeke, Cedric; De Backer, William; De Backer, Jan; Lee, James

2018-02-19

Long-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV 1 ) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS. Paired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV 1 of >10% compared to baseline FEV 1 post LTx. Multifactor analysis correlated declining FEV 1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS. The FEV 1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV 1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P < .05), whereas no pulmonary function testing parameters could. Using ML methods (support vector machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters. ML utilizing qCT could discern distinct mechanisms driving FEV 1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Measurement of bone adjacent to tibial shaft fracture.

PubMed

Findlay, S C; Eastell, R; Ingle, B M

2002-12-01

Delayed union and non-union are common complications after fracture of the tibial shaft. Response of the surrounding bone as a fracture heals could be monitored using techniques currently used in the study of osteoporosis. The aims of our study were to: (1) evaluate the decrement in bone measurements made close to the fracture using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral quantitative computed tomography (pQCT); (2) compare values for fractured versus non-fractured leg to determine the duration of decrement in bone measurements; and (3) calculate short-term precision in DXA, QUS and pQCT in order to calculate the ratio of decrement to precision (response ratio, RR) to determine the optimal test for monitoring changes after tibial fracture. The biggest decrement in bone measurements at the ipsilateral limb of 28 patients with tibial shaft fracture was observed at the pQCT tibial trabecular sites (distal = 19%, p<0.0001; proximal 5% = 21%, p<0.001; proximal 10% = 28%, p<0.001) and the ultradistal tibia/fibula measured by DXA (19%, p<0.0001). When comparing Z-scores, the magnitude of decrements at the ipsilateral limb was bigger for variables measured directly at the tibia, both proximal and distal to the fracture. The magnitude of the decrement in ultradistal tibia/fibula BMD decreased as the time since fracture increased ( r = 0.55). When response ratios are considered, pQCT measurements at the distal tibia (RR 6-8) and proximal 5% and 10% trabecular sites (RR 5 and 9 respectively) were found to be the most sensitive to change. Therefore, pQCT of the trabecular regions of either the proximal or distal tibia should prove the most sensitive measurement for monitoring changes in bone adjacent to a tibial shaft fracture.

Advanced imaging of the macrostructure and microstructure of bone

NASA Technical Reports Server (NTRS)

Genant, H. K.; Gordon, C.; Jiang, Y.; Link, T. M.; Hans, D.; Majumdar, S.; Lang, T. F.

2000-01-01

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other. Copyright 2000 S. Karger AG, Basel.

Does peripheral quantitative computed tomography ignore tissue density of cancellous bone?

PubMed

Banse, X; Devogelaer, J P

2002-01-01

The purpose of this work was to determine the capacity of peripheral quantitative computed tomography (pQCT) to accurately measure the true physical properties of vertebral cancellous bone samples and to predict their stiffness. pQCT bone mineral density (BMD) was first measured in ideal conditions. Ten cubic specimens of vertebral cancellous bone (10 x 10 x 10 mm) were washed with a water jet, defatted, and scanned in saline after elimination of air bubbles; thirteen slices were obtained. Seventy-one unprepared cylindrical samples were scanned in more realistic conditions, which allow further biomechanical testing. After extraction from the vertebral body, the samples were pushed into a plastic tube (no effort was made to remove the marrow or air bubbles), and only four slices were obtained to reduce the duration of scan. For the 81 samples, the true bone volume fraction (BV/TV, %), true apparent density (rho(app), g/cm(3)), and tissue density (rho(tiss), g/cm(3)) (an indicator of the degree of mineralization of the matrix) were then measured using Archimedes principle. rho(app) was closely correlated to BV/TV (r(2) = 0.97). rho(tiss) (1.58 +/- 0.08 g/cm(2)) was almost constant but had some influence on rho(app) (r(2) = 0.03, p < 0.001). The pQCT BMD predicted accurately rho(app) (r(2) = 0.96) and BV/TV (r(2) = 0.93) for the cylinders. For the cubes, in ideal conditions, the same correlations were even better (r(2) > 0.99, both). Analysis of covariance indicated no difference (p > 0.05) in the regressions due to preparation of the samples. The stiffness was better predicted by the true rho(app) (r(2) = 0.87) than by BV/TV (r(2) = 0.83), indicating that stiffness was influenced by small differences in the tissue density. Consequently, the correlation between pQCT BMD and stiffness was excellent (r(2) = 0.84). The fact that pQCT did not ignore this tissue density information compensated for the inaccuracies linked to realistic scanning conditions of the cylinder.

Reconstruction algorithm for polychromatic CT imaging: application to beam hardening correction

NASA Technical Reports Server (NTRS)

Yan, C. H.; Whalen, R. T.; Beaupre, G. S.; Yen, S. Y.; Napel, S.

2000-01-01

This paper presents a new reconstruction algorithm for both single- and dual-energy computed tomography (CT) imaging. By incorporating the polychromatic characteristics of the X-ray beam into the reconstruction process, the algorithm is capable of eliminating beam hardening artifacts. The single energy version of the algorithm assumes that each voxel in the scan field can be expressed as a mixture of two known substances, for example, a mixture of trabecular bone and marrow, or a mixture of fat and flesh. These assumptions are easily satisfied in a quantitative computed tomography (QCT) setting. We have compared our algorithm to three commonly used single-energy correction techniques. Experimental results show that our algorithm is much more robust and accurate. We have also shown that QCT measurements obtained using our algorithm are five times more accurate than that from current QCT systems (using calibration). The dual-energy mode does not require any prior knowledge of the object in the scan field, and can be used to estimate the attenuation coefficient function of unknown materials. We have tested the dual-energy setup to obtain an accurate estimate for the attenuation coefficient function of K2 HPO4 solution.

Quantitative computed tomography-based predictions of vertebral strength in anterior bending.

PubMed

Buckley, Jenni M; Cheng, Liu; Loo, Kenneth; Slyfield, Craig; Xu, Zheng

2007-04-20

This study examined the ability of QCT-based structural assessment techniques to predict vertebral strength in anterior bending. The purpose of this study was to compare the abilities of QCT-based bone mineral density (BMD), mechanics of solids models (MOS), e.g., bending rigidity, and finite element analyses (FE) to predict the strength of isolated vertebral bodies under anterior bending boundary conditions. Although the relative performance of QCT-based structural measures is well established for uniform compression, the ability of these techniques to predict vertebral strength under nonuniform loading conditions has not yet been established. Thirty human thoracic vertebrae from 30 donors (T9-T10, 20 female, 10 male; 87 +/- 5 years of age) were QCT scanned and destructively tested in anterior bending using an industrial robot arm. The QCT scans were processed to generate specimen-specific FE models as well as trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and MOS measures, such as axial and bending rigidities. Vertebral strength in anterior bending was poorly to moderately predicted by QCT-based BMD and MOS measures (R2 = 0.14-0.22). QCT-based FE models were better strength predictors (R2 = 0.34-0.40); however, their predictive performance was not statistically different from MOS bending rigidity (P > 0.05). Our results suggest that the poor clinical performance of noninvasive structural measures may be due to their inability to predict vertebral strength under bending loads. While their performance was not statistically better than MOS bending rigidities, QCT-based FE models were moderate predictors of both compressive and bending loads at failure, suggesting that this technique has the potential for strength prediction under nonuniform loads. The current FE modeling strategy is insufficient, however, and significant modifications must be made to better mimic whole bone elastic and inelastic material behavior.

Quantitative Computed Tomography (QCT) derived Bone Mineral Density (BMD) in finite element studies: a review of the literature.

PubMed

Knowles, Nikolas K; Reeves, Jacob M; Ferreira, Louis M

2016-12-01

Finite element modeling of human bone provides a powerful tool to evaluate a wide variety of outcomes in a highly repeatable and parametric manner. These models are most often derived from computed tomography data, with mechanical properties related to bone mineral density (BMD) from the x-ray energy attenuation provided from this data. To increase accuracy, many researchers report the use of quantitative computed tomography (QCT), in which a calibration phantom is used during image acquisition to improve the estimation of BMD. Since model accuracy is dependent on the methods used in the calculation of BMD and density-mechanical property relationships, it is important to use relationships developed for the same anatomical location and using the same scanner settings, as these may impact model accuracy. The purpose of this literature review is to report the relationships used in the conversion of QCT equivalent density measures to ash, apparent, and/or tissue densities in recent finite element (FE) studies used in common density-modulus relationships. For studies reporting experimental validation, the validation metrics and results are presented. Of the studies reviewed, 29% reported the use of a dipotassium phosphate (K 2 HPO 4 ) phantom, 47% a hydroxyapatite (HA) phantom, 13% did not report phantom type, 7% reported use of both K 2 HPO 4 and HA phantoms, and 4% alternate phantom types. Scanner type and/or settings were omitted or partially reported in 31% of studies. The majority of studies used densitometric and/or density-modulus relationships derived from different anatomical locations scanned in different scanners with different scanner settings. The methods used to derive various densitometric relationships are reported and recommendations are provided toward the standardization of reporting metrics. This review assessed the current state of QCT-based FE modeling with use of clinical scanners. It was found that previously developed densitometric relationships vary by anatomical location, scanner type and settings. Reporting of all parameters used when referring to previously developed relationships, or in the development of new relationships, may increase the accuracy and repeatability of future FE models.

A calibration methodology of QCT BMD for human vertebral body with registered micro-CT images.

PubMed

Dall'Ara, E; Varga, P; Pahr, D; Zysset, P

2011-05-01

The accuracy of QCT-based homogenized finite element (FE) models is strongly related to the accuracy of the prediction of bone volume fraction (BV/TV) from bone mineral density (BMD). The goal of this study was to establish a calibration methodology to relate the BMD computed with QCT with the BV/TV computed with micro-CT (microCT) over a wide range of bone mineral densities and to investigate the effect of region size in which BMD and BV/TV are computed. Six human vertebral bodies were dissected from the spine of six donors and scanned submerged in water with QCT (voxel size: 0.391 x 0.391 x 0.450 mm3) and microCT (isotropic voxel size: 0.018(3) mm3). The microCT images were segmented with a single level threshold. Afterward, QCT-grayscale, microCT-grayscale, and microCT-segmented images were registered. Two isotropic grids of 1.230 mm (small) and 4.920 mm (large) were superimposed on every image, and QCT(BMD) was compared both with microCT(BMD) and microCT(BV/TV) for each grid cell. The ranges of QCT(BMD) for large and small regions were 9-559 mg/cm3 and -90 to 1006 mg/cm3, respectively. QCT(BMD) was found to overestimate microCT(BMD). No significant differences were found between the QCT(BMD)-microCT(BV/TV) regression parameters of the two grid sizes. However, the R2 was higher, and the standard error of the estimate (SEE) was lower for large regions when compared to small regions. For the pooled data, an extrapolated QCTBMD value equal to 1062 mg/ cm3 was found to correspond to 100% microCT(BV/TV). A calibration method was defined to evaluate BV/TV from QCTBMD values for cortical and trabecular bone in vitro. The QCT(BMD-microCT(BV/TV) calibration was found to be dependent on the scanned vertebral section but not on the size of the regions. However, the higher SEE computed for small regions suggests that the deleterious effect of QCT image noise on FE modelling increases with decreasing voxel size.

Contrast agent enhanced pQCT of articular cartilage

NASA Astrophysics Data System (ADS)

Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

2007-02-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.

Please Don't Move-Evaluating Motion Artifact From Peripheral Quantitative Computed Tomography Scans Using Textural Features.

PubMed

Rantalainen, Timo; Chivers, Paola; Beck, Belinda R; Robertson, Sam; Hart, Nicolas H; Nimphius, Sophia; Weeks, Benjamin K; McIntyre, Fleur; Hands, Beth; Siafarikas, Aris

Most imaging methods, including peripheral quantitative computed tomography (pQCT), are susceptible to motion artifacts particularly in fidgety pediatric populations. Methods currently used to address motion artifact include manual screening (visual inspection) and objective assessments of the scans. However, previously reported objective methods either cannot be applied on the reconstructed image or have not been tested for distal bone sites. Therefore, the purpose of the present study was to develop and validate motion artifact classifiers to quantify motion artifact in pQCT scans. Whether textural features could provide adequate motion artifact classification performance in 2 adolescent datasets with pQCT scans from tibial and radial diaphyses and epiphyses was tested. The first dataset was split into training (66% of sample) and validation (33% of sample) datasets. Visual classification was used as the ground truth. Moderate to substantial classification performance (J48 classifier, kappa coefficients from 0.57 to 0.80) was observed in the validation dataset with the novel texture-based classifier. In applying the same classifier to the second cross-sectional dataset, a slight-to-fair (κ = 0.01-0.39) classification performance was observed. Overall, this novel textural analysis-based classifier provided a moderate-to-substantial classification of motion artifact when the classifier was specifically trained for the measurement device and population. Classification based on textural features may be used to prescreen obviously acceptable and unacceptable scans, with a subsequent human-operated visual classification of any remaining scans. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT.

PubMed

Nishiyama, K K; Macdonald, H M; Hanley, D A; Boyd, S K

2013-05-01

High-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of distal radius and tibia bone microarchitecture and finite element (FE) estimates of bone strength performed well at classifying postmenopausal women with and without previous fracture. The HR-pQCT measurements outperformed dual energy x-ray absorptiometry (DXA) at classifying forearm fractures and fractures at other skeletal sites. Areal bone mineral density (aBMD) is the primary measurement used to assess osteoporosis and fracture risk; however, it does not take into account bone microarchitecture, which also contributes to bone strength. Thus, our objective was to determine if bone microarchitecture measured with HR-pQCT and FE estimates of bone strength could classify women with and without low-trauma fractures. We used HR-pQCT to assess bone microarchitecture at the distal radius and tibia in 44 postmenopausal women with a history of low-trauma fracture and 88 age-matched controls from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) study. We estimated bone strength using FE analysis and simulated distal radius aBMD from the HR-pQCT scans. Femoral neck (FN) and lumbar spine (LS) aBMD were measured with DXA. We used support vector machines (SVM) and a tenfold cross-validation to classify the fracture cases and controls and to determine accuracy. The combination of HR-pQCT measures of microarchitecture and FE estimates of bone strength had the highest area under the receiver operating characteristic (ROC) curve of 0.82 when classifying forearm fractures compared to an area under the curve (AUC) of 0.71 from DXA-derived aBMD of the forearm and 0.63 from FN and spine DXA. For all fracture types, FE estimates of bone strength at the forearm alone resulted in an AUC of 0.69. Models based on HR-pQCT measurements of bone microarchitecture and estimates of bone strength performed better than DXA-derived aBMD at classifying women with and without prior fracture. In future, these models may improve prediction of individuals at risk of low-trauma fracture.

A novel interpolation approach for the generation of 3D-geometric digital bone models from image stacks

PubMed Central

Mittag, U.; Kriechbaumer, A.; Rittweger, J.

2017-01-01

The authors propose a new 3D interpolation algorithm for the generation of digital geometric 3D-models of bones from existing image stacks obtained by peripheral Quantitative Computed Tomography (pQCT) or Magnetic Resonance Imaging (MRI). The technique is based on the interpolation of radial gray value profiles of the pQCT cross sections. The method has been validated by using an ex-vivo human tibia and by comparing interpolated pQCT images with images from scans taken at the same position. A diversity index of <0.4 (1 meaning maximal diversity) even for the structurally complex region of the epiphysis, along with the good agreement of mineral-density-weighted cross-sectional moment of inertia (CSMI), demonstrate the high quality of our interpolation approach. Thus the authors demonstrate that this interpolation scheme can substantially improve the generation of 3D models from sparse scan sets, not only with respect to the outer shape but also with respect to the internal gray-value derived material property distribution. PMID:28574415

Validation of calcaneus trabecular microstructure measurements by HR-pQCT.

PubMed

Metcalf, Louis M; Dall'Ara, Enrico; Paggiosi, Margaret A; Rochester, John R; Vilayphiou, Nicolas; Kemp, Graham J; McCloskey, Eugene V

2018-01-01

Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TV d ); trabecular number, Tb.N; derived trabecular thickness, Tb.Th d ; derived trabecular spacing, Tb.Sp d ) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TV d was strongly correlated with micro-CT BV/TV (r 2 =0.95-0.98, RMSE=1%), but BV/TV d was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r 2 =0.61, RMSE=0.15mm -1 ). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm -1 ; r 2 =0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm -1 ; r 2 ≤0.08, p≥0.21 for inferior regions). Tb.Sp d was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Th d was also underestimated and moderately correlated (r 2 =0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. Calcaneus trabecular BV/TV d and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

CT acquisition technique and quantitative analysis of the lung parenchyma: variability and corrections

NASA Astrophysics Data System (ADS)

Zheng, Bin; Leader, J. K.; Coxson, Harvey O.; Scuirba, Frank C.; Fuhrman, Carl R.; Balkan, Arzu; Weissfeld, Joel L.; Maitz, Glenn S.; Gur, David

2006-03-01

The fraction of lung voxels below a pixel value "cut-off" has been correlated with pathologic estimates of emphysema. We performed a "standard" quantitative CT (QCT) lung analysis using a -950 HU cut-off to determine the volume fraction of emphysema (below the cut-off) and a "corrected" QCT analysis after removing small group (5 and 10 pixels) of connected pixels ("blobs") below the cut-off. CT examinations two dataset of 15 subjects each with a range of visible emphysema and pulmonary obstruction were acquired at "low-dose and conventional dose reconstructed using a high-spatial frequency kernel at 2.5 mm section thickness for the same subject. The "blob" size (i.e., connected-pixels) removed was inversely related to the computed fraction of emphysema. The slopes of emphysema fraction versus blob size were 0.013, 0.009, and 0.005 for subjects with both no emphysema and no pulmonary obstruction, moderate emphysema and pulmonary obstruction, and severe emphysema and severe pulmonary obstruction, respectively. The slopes of emphysema fraction versus blob size were 0.008 and 0.006 for low-dose and conventional CT examinations, respectively. The small blobs of pixels removed are most likely CT image artifacts and do not represent actual emphysema. The magnitude of the blob correction was appropriately associated with COPD severity. The blob correction appears to be applicable to QCT analysis in low-dose and conventional CT exams.

Robust QCT/FEA Models of Proximal Femur Stiffness and Fracture Load During a Sideways Fall on the Hip

PubMed Central

Dragomir-Daescu, Dan; Buijs, Jorn Op Den; McEligot, Sean; Dai, Yifei; Entwistle, Rachel C.; Salas, Christina; Melton, L. Joseph; Bennet, Kevin E.; Khosla, Sundeep; Amin, Shreyasee

2013-01-01

Clinical implementation of quantitative computed tomography-based finite element analysis (QCT/FEA) of proximal femur stiffness and strength to assess the likelihood of proximal femur (hip) fractures requires a unified modeling procedure, consistency in predicting bone mechanical properties, and validation with realistic test data that represent typical hip fractures, specifically, a sideways fall on the hip. We, therefore, used two sets (n = 9, each) of cadaveric femora with bone densities varying from normal to osteoporotic to build, refine, and validate a new class of QCT/FEA models for hip fracture under loading conditions that simulate a sideways fall on the hip. Convergence requirements of finite element models of the first set of femora led to the creation of a new meshing strategy and a robust process to model proximal femur geometry and material properties from QCT images. We used a second set of femora to cross-validate the model parameters derived from the first set. Refined models were validated experimentally by fracturing femora using specially designed fixtures, load cells, and high speed video capture. CT image reconstructions of fractured femora were created to classify the fractures. The predicted stiffness (cross-validation R2 = 0.87), fracture load (cross-validation R2 = 0.85), and fracture patterns (83% agreement) correlated well with experimental data. PMID:21052839

Tibial Geometry in Individuals with Neurofibromatosis Type 1 without Anterolateral Bowing of the Lower Leg Using Peripheral Quantitative Computed Tomography

PubMed Central

Stevenson, David A.; Viskochil, David H.; Carey, John C.; Slater, Hillarie; Murray, Mary; Sheng, Xiaoming; D’Astous, Jacques; Hanson, Heather; Schorry, Elizabeth; Moyer-Mileur, Laurie J.

2008-01-01

Introduction Lower leg bowing with tibial pseudarthrosis is associated with neurofibromatosis type 1 (NF1). The objective of the study is to determine if the geometry of the lower limb in individuals with neurofibromatosis type 1 (NF1) differs from controls, and to characterize the osseous components of the tibia in NF1. Methods Peripheral quantitative computed tomography (pQCT) of the lower limb was performed (90 individuals with NF1 without tibial and/or fibular dysplasia: 474 healthy individuals without NF1). Subjects were 4–18 years of age. Individuals with NF1 were compared to controls using an analysis-of-covariance with a fixed set of covariates (age, weight, height, Tanner stage, and gender). Results Using pQCT, NF1 individuals without bowing of the lower leg have smaller periosteal circumferences (p<0.0001), smaller cortical area (p<0.0001), and decreased tibial cortical and trabecular bone mineral content (BMC) (p<0.0001) compared to controls. Discussion Individuals with NF1 have a different geometry of the lower leg compared to healthy controls suggesting that NF1 haploinsufficiency impacts bone homeostasis although not resulting in overt anterolateral bowing of the lower leg. PMID:19118659

A novel registration-based methodology for prediction of trabecular bone fabric from clinical QCT: A comprehensive analysis

PubMed Central

Reyes, Mauricio; Zysset, Philippe

2017-01-01

Osteoporosis leads to hip fractures in aging populations and is diagnosed by modern medical imaging techniques such as quantitative computed tomography (QCT). Hip fracture sites involve trabecular bone, whose strength is determined by volume fraction and orientation, known as fabric. However, bone fabric cannot be reliably assessed in clinical QCT images of proximal femur. Accordingly, we propose a novel registration-based estimation of bone fabric designed to preserve tensor properties of bone fabric and to map bone fabric by a global and local decomposition of the gradient of a non-rigid image registration transformation. Furthermore, no comprehensive analysis on the critical components of this methodology has been previously conducted. Hence, the aim of this work was to identify the best registration-based strategy to assign bone fabric to the QCT image of a patient’s proximal femur. The normalized correlation coefficient and curvature-based regularization were used for image-based registration and the Frobenius norm of the stretch tensor of the local gradient was selected to quantify the distance among the proximal femora in the population. Based on this distance, closest, farthest and mean femora with a distinction of sex were chosen as alternative atlases to evaluate their influence on bone fabric prediction. Second, we analyzed different tensor mapping schemes for bone fabric prediction: identity, rotation-only, rotation and stretch tensor. Third, we investigated the use of a population average fabric atlas. A leave one out (LOO) evaluation study was performed with a dual QCT and HR-pQCT database of 36 pairs of human femora. The quality of the fabric prediction was assessed with three metrics, the tensor norm (TN) error, the degree of anisotropy (DA) error and the angular deviation of the principal tensor direction (PTD). The closest femur atlas (CTP) with a full rotation (CR) for fabric mapping delivered the best results with a TN error of 7.3 ± 0.9%, a DA error of 6.6 ± 1.3% and a PTD error of 25 ± 2°. The closest to the population mean femur atlas (MTP) using the same mapping scheme yielded only slightly higher errors than CTP for substantially less computing efforts. The population average fabric atlas yielded substantially higher errors than the MTP with the CR mapping scheme. Accounting for sex did not bring any significant improvements. The identified fabric mapping methodology will be exploited in patient-specific QCT-based finite element analysis of the proximal femur to improve the prediction of hip fracture risk. PMID:29176881

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

NASA Technical Reports Server (NTRS)

Chang, Katarina L.; Pennline, James A.

2013-01-01

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.

Trabecular Bone Score (TBS)—A Novel Method to Evaluate Bone Microarchitectural Texture in Patients With Primary Hyperparathyroidism

PubMed Central

Boutroy, Stephanie; Zhang, Chiyuan; McMahon, Donald Jay; Zhou, Bin; Wang, Ji; Udesky, Julia; Cremers, Serge; Sarquis, Marta; Guo, Xiang-Dong Edward; Hans, Didier

2013-01-01

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. Objective: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. Design and Setting: This was a cross-sectional study conducted in a referral center. Patients: Participants were 22 postmenopausal women with PHPT. Main Outcome Measures: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. Results: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. Conclusion: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT. PMID:23526463

Determining Metacarpophalangeal Flexion Angle Tolerance for Reliable Volumetric Joint Space Measurements by High-resolution Peripheral Quantitative Computed Tomography.

PubMed

Tom, Stephanie; Frayne, Mark; Manske, Sarah L; Burghardt, Andrew J; Stok, Kathryn S; Boyd, Steven K; Barnabe, Cheryl

2016-10-01

The position-dependence of a method to measure the joint space of metacarpophalangeal (MCP) joints using high-resolution peripheral quantitative computed tomography (HR-pQCT) was studied. Cadaveric MCP were imaged at 7 flexion angles between 0 and 30 degrees. The variability in reproducibility for mean, minimum, and maximum joint space widths and volume measurements was calculated for increasing degrees of flexion. Root mean square coefficient of variance values were < 5% under 20 degrees of flexion for mean, maximum, and volumetric joint spaces. Values for minimum joint space width were optimized under 10 degrees of flexion. MCP joint space measurements should be acquired at < 10 degrees of flexion in longitudinal studies.

The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood

NASA Technical Reports Server (NTRS)

Les, C. M.; Whalen, R. T.; Beaupre, G. S.; Yan, C. H.; Cleek, T. M.; Wills, J. S.

2002-01-01

Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

Quantitative computed tomography of the lungs and airways in healthy nonsmoking adults.

PubMed

Zach, Jordan Alexander; Newell, John D; Schroeder, Joyce; Murphy, James R; Curran-Everett, Douglas; Hoffman, Eric A; Westgate, Philip M; Han, MeiLan K; Silverman, Edwin K; Crapo, James D; Lynch, David A

2012-10-01

The purposes of this study were to evaluate the reference range of quantitative computed tomography (QCT) measures of lung attenuation and airway parameter measurements in healthy nonsmoking adults and to identify sources of variation in those measures and possible means to adjust for them. Within the COPDGene study, 92 healthy non-Hispanic white nonsmokers (29 men, 63 women; mean [SD] age, 62.7 [9.0] years; mean [SD] body mass index [BMI], 28.1 [5.1] kg/m(2)) underwent volumetric computed tomography (CT) at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low-attenuation areas were defined as lung tissue with attenuation values -950 Hounsfield units or less on inspiratory CT (LAA(I-950)). Expiratory low-attenuation areas were defined as lung tissue -856 Hounsfield units or less on expiratory CT (LAA(E-856)). We used simple linear regression to determine the impact of age and sex on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLC(CT) and FRC(CT)), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness, inner luminal area, wall area percentage (WA%), and standardized thickness of an airway with inner perimeter of 10 mm (Pi10). Mean (SD) %LAA(I-950) was 2.0% (2.7%), and mean (SD) %LAA(E-856) was 9.2% (6.8%). Mean (SD) %LAA(I-950) was 3.6% (3.2%) in men, compared with 1.3% (2.0%) in women (P < 0.001). The %LAA(I-950) did not change significantly with age (P = 0.08) or BMI (P = 0.52). %LAA(E-856) did not show any independent relationship with age (P = 0.33), sex (P = 0.70), or BMI (P = 0.32). On multivariate analysis, %LAA(I-950) showed a direct relationship to TLC(CT) (P = 0.002) and an inverse relationship to mean tracheal air attenuation (P = 0.003), and %LAA(E-856) was related to age (P = 0.001), FRC(CT) (P = 0.007), and scanner type (P < 0.001). Multivariate analysis of segmental airways showed that inner luminal area and WA% were significantly related to TLC(CT) (P < 0.001) and age (0.006). Moreover, WA% was associated with sex (P = 0.05), axial pixel size (P = 0.03), and slice interval (P = 0.04). Lastly, airway wall thickness was strongly influenced by axial pixel size (P < 0.001). Although the attenuation characteristics of normal lung differ by age and sex, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based QCT parameters include depth of inspiration/expiration and scanner type. Tracheal air attenuation may partially correct variation because of scanner type. Sources of variation in QCT airway measurements may include age, sex, BMI, depth of inspiration, and spatial resolution.

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal.

PubMed

Chaplais, Elodie; Greene, David; Hood, Anita; Telfer, Scott; du Toit, Verona; Singh-Grewal, Davinder; Burns, Joshua; Rome, Keith; Schiferl, Daniel J; Hendry, Gordon J

2014-07-19

Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec(-1). The reference line was positioned at the most distal portion of the 2(nd) metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2(nd) metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures.

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

PubMed Central

2014-01-01

Background Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI – mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI – mid shaft (ICC 0.99; CV% 3.2). Conclusions The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures. PMID:25037451

Relationship between lung function and quantitative computed tomographic parameters of airway remodeling, air trapping, and emphysema in patients with asthma and chronic obstructive pulmonary disease: A single-center study.

PubMed

Hartley, Ruth A; Barker, Bethan L; Newby, Chris; Pakkal, Mini; Baldi, Simonetta; Kajekar, Radhika; Kay, Richard; Laurencin, Marie; Marshall, Richard P; Sousa, Ana R; Parmar, Harsukh; Siddiqui, Salman; Gupta, Sumit; Brightling, Chris E

2016-05-01

There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation. Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization. Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001). Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001). Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, -964 [SD, 19.62] vs asthmatic patients: mean, -937 [SD, 22.7] and healthy subjects: mean, -937 [SD, 17.1], P < .001). Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping. Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors. Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air trapping. In asthmatic patients and patients with COPD, lung function impairment is strongly associated with air trapping, with a contribution from proximal airway narrowing in asthmatic patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A customized protocol to assess bone quality in the metacarpal head, metacarpal shaft and distal radius: a high resolution peripheral quantitative computed tomography precision study.

PubMed

Feehan, Lynne; Buie, Helen; Li, Linda; McKay, Heather

2013-12-24

High Resolution-Peripheral Quantitative Computed Tomography (HR-pQCT) is an emerging technology for evaluation of bone quality in Rheumatoid Arthritis (RA). However, there are limitations with standard HR-pQCT imaging protocols for examination of regions of bone commonly affected in RA. We developed a customized protocol for evaluation of volumetric bone mineral density (vBMD) and microstructure at the metacarpal head (MH), metacarpal shaft (MS) and ultra-ultra-distal (UUD) radius; three sites commonly affected in RA. The purpose was to evaluate short-term measurement precision for bone density and microstructure at these sites. 12 non-RA participants, individuals likely to have no pre-existing bone damage, consented to participate [8 females, aged 23 to 71 y [median (IQR): 44 (28) y]. The custom protocol includes more comfortable/stable positioning and adapted cortical segmentation and direct transformation analysis methods. Dominant arm MH, MS and UUD radius scans were completed on day one; repeated twice (with repositioning) three to seven days later. Short-term precision for repeated measures was explored using intraclass correlational coefficient (ICC), mean coefficient of variation (CV%), root mean square coefficient of variation (RMSCV%) and least significant change (LSC%95). Bone density and microstructure precision was excellent: ICCs varied from 0.88 (MH2 trabecular number) to .99 (MS3 polar moment of inertia); CV% varied from < 1 (MS2 vBMD) to 6 (MS3 marrow space diameter); RMSCV% varied from < 1 (MH2 full bone vBMD) to 7 (MS3 marrow space diameter); and LSC%95 varied from 2 (MS2 full bone vBMD to 21 (MS3 marrow space diameter). Cortical porosity measures were the exception; RMSCV% varying from 19 (MS3) to 42 (UUD). No scans were stopped for discomfort. 5% (5/104) were repeated due to motion during imaging. 8% (8/104) of final images had motion artifact graded > 3 on 5 point scale. In our facility, this custom protocol extends the potential for in vivo HR-pQCT imaging to assess, with high precision, regional differences in bone quality at three sites commonly affected in RA. Our methods are easy to adopt and we recommend other users of HR-pQCT consider this protocol for further evaluations of its precision and feasibility in their imaging facilities.

Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women.

PubMed

Edwards, M H; Robinson, D E; Ward, K A; Javaid, M K; Walker-Bone, K; Cooper, C; Dennison, E M

2016-07-01

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone. Copyright © 2016. Published by Elsevier Inc.

Peripheral Quantitative CT (pQCT) Using a Dedicated Extremity Cone-Beam CT Scanner

PubMed Central

Muhit, A. A.; Arora, S.; Ogawa, M.; Ding, Y.; Zbijewski, W.; Stayman, J. W.; Thawait, G.; Packard, N.; Senn, R.; Yang, D.; Yorkston, J.; Bingham, C.O.; Means, K.; Carrino, J. A.; Siewerdsen, J. H.

2014-01-01

Purpose We describe the initial assessment of the peripheral quantitative CT (pQCT) imaging capabilities of a cone-beam CT (CBCT) scanner dedicated to musculoskeletal extremity imaging. The aim is to accurately measure and quantify bone and joint morphology using information automatically acquired with each CBCT scan, thereby reducing the need for a separate pQCT exam. Methods A prototype CBCT scanner providing isotropic, sub-millimeter spatial resolution and soft-tissue contrast resolution comparable or superior to standard multi-detector CT (MDCT) has been developed for extremity imaging, including the capability for weight-bearing exams and multi-mode (radiography, fluoroscopy, and volumetric) imaging. Assessment of pQCT performance included measurement of bone mineral density (BMD), morphometric parameters of subchondral bone architecture, and joint space analysis. Measurements employed phantoms, cadavers, and patients from an ongoing pilot study imaged with the CBCT prototype (at various acquisition, calibration, and reconstruction techniques) in comparison to MDCT (using pQCT protocols for analysis of BMD) and micro-CT (for analysis of subchondral morphometry). Results The CBCT extremity scanner yielded BMD measurement within ±2–3% error in both phantom studies and cadaver extremity specimens. Subchondral bone architecture (bone volume fraction, trabecular thickness, degree of anisotropy, and structure model index) exhibited good correlation with gold standard micro-CT (error ~5%), surpassing the conventional limitations of spatial resolution in clinical MDCT scanners. Joint space analysis demonstrated the potential for sensitive 3D joint space mapping beyond that of qualitative radiographic scores in application to non-weight-bearing versus weight-bearing lower extremities and assessment of phalangeal joint space integrity in the upper extremities. Conclusion The CBCT extremity scanner demonstrated promising initial results in accurate pQCT analysis from images acquired with each CBCT scan. Future studies will include improved x-ray scatter correction and image reconstruction techniques to further improve accuracy and to correlate pQCT metrics with known pathology. PMID:25076823

A comparison of peripheral imaging technologies for bone and muscle quantification: a technical review of image acquisition

PubMed Central

Wong, A.K.O.

2016-01-01

The choice of an appropriate imaging technique to quantify bone, muscle, or muscle adiposity needs to be guided by a thorough understanding of its competitive advantages over other modalities balanced by its limitations. This review details the technical machinery and methods behind peripheral quantitative computed tomography (pQCT), high-resolution (HR)-pQCT, and magnetic resonance imaging (MRI) that drive successful depiction of bone and muscle morphometry, densitometry, and structure. It discusses a number of image acquisition settings, the challenges associated with using one versus another, and compares the risk-benefits across the different modalities. Issues related to all modalities including partial volume artifact, beam hardening, calibration, and motion assessment are also detailed. The review further provides data and images to illustrate differences between methods to better guide the reader in selecting an imaging method strategically. Overall, investigators should be cautious of the impact of imaging parameters on image signal or contrast-to-noise-ratios, and the need to report these settings in future publications. The effect of motion should be assessed on images and a decision made to exclude prior to segmentation. A more standardized approach to imaging bone and muscle on pQCT and MRI could enhance comparability across studies and could improve the quality of meta-analyses. PMID:27973379

A comparison of peripheral imaging technologies for bone and muscle quantification: a technical review of image acquisition.

PubMed

Wong, A K

2016-12-14

The choice of an appropriate imaging technique to quantify bone, muscle, or muscle adiposity needs to be guided by a thorough understanding of its competitive advantages over other modalities balanced by its limitations. This review details the technical machinery and methods behind peripheral quantitative computed tomography (pQCT), high-resolution (HR)-pQCT, and magnetic resonance imaging (MRI) that drive successful depiction of bone and muscle morphometry, densitometry, and structure. It discusses a number of image acquisition settings, the challenges associated with using one versus another, and compares the risk-benefits across the different modalities. Issues related to all modalities including partial volume artifact, beam hardening, calibration, and motion assessment are also detailed. The review further provides data and images to illustrate differences between methods to better guide the reader in selecting an imaging method strategically. Overall, investigators should be cautious of the impact of imaging parameters on image signal or contrast-to-noise-ratios, and the need to report these settings in future publications. The effect of motion should be assessed on images and a decision made to exclude prior to segmentation. A more standardized approach to imaging bone and muscle on pQCT and MRI could enhance comparability across studies and could improve the quality of meta-analyses.

Individual Trabecula Segmentation (ITS)-Based Morphological Analyses and Micro Finite Element Analysis of HR-pQCT Images Discriminate Postmenopausal Fragility Fractures Independent of DXA Measurements

PubMed Central

Liu, X. Sherry; Stein, Emily M.; Zhou, Bin; Zhang, Chiyuan A.; Nickolas, Thomas L.; Cohen, Adi; Thomas, Valerie; McMahon, Donald J.; Cosman, Felicia; Nieves, Jeri; Shane, Elizabeth; Guo, X. Edward

2011-01-01

Osteoporosis is typically diagnosed by dual energy x-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n=68) and without (n=101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabeculae segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by micro finite element analysis (μFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number and connectivity were directly associated with bone stiffness. In contrast, rod volume, number and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and μFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and μFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. PMID:22072446

Normative Standards for HRpQCT Parameters in Chinese Men and Women.

PubMed

Zhu, Tracy Y; Yip, Benjamin Hk; Hung, Vivian Wy; Choy, Carol Wy; Cheng, Ka-Lo; Kwok, Timothy Cy; Cheng, Jack Cy; Qin, Ling

2018-06-12

Assessing bone architecture using high resolution peripheral quantitative computed tomography (HRpQCT) has the potential to improve fracture risk assessment. The Normal Reference Study aimed to establish sex-specific reference centile curves for HRpQCT parameters. This was an age-stratified cross-sectional study and 1,072 ambulatory Chinese men (n = 544) and women (n = 528) aged 20-79yrs, who were free from conditions and medications that could affect bone metabolism and had no history of fragility fracture, were recruited from local communities of Hong Kong. Reference centile curves for each HRpQCT parameter were constructed using Generalized Additive Models for Location, Scale and Shape with age as the only explanatory variable. Patterns of reference centile curves reflected age-related changes of bone density, microarchitecture, and estimated bone strength. In both sexes, loss of cortical bone was only evident in mid-adulthood, particularly in women with a more rapid fashion probably concurrent with the onset of menopause. In contrast, loss of trabecular bone was subtle or gradual or occurred at an earlier age. Expected values of HRpQCT parameters for a defined sex and age, and a defined percentile or z-score were obtained from these curves. T-scores were calculated using the population with the peak values as the reference and reflected age- or menopause-related bone loss in an older individual or the room to reach the peak potential in a younger individual. These reference centile curves produced a standard describing a norm or desirable target that enables value clinical judgements. Percentiles, z-scores and T-scores would be helpful in detecting abnormalities in bone density and microarchitecture arising from various conditions and establishing entry criteria for clinical trials. They also hold the potential to refine the diagnosis of osteoporosis and assessment of fracture risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Investigating the Effects of Motion Streaks on pQCT-Derived Leg Muscle Density and Its Association With Fractures.

PubMed

Chan, Adrian C H; Adachi, Jonathan D; Papaioannou, Alexandra; Wong, Andy Kin On

Lower peripheral quantitative computed tomography (pQCT)-derived leg muscle density has been associated with fragility fractures in postmenopausal women. Limb movement during image acquisition may result in motion streaks in muscle that could dilute this relationship. This cross-sectional study examined a subset of women from the Canadian Multicentre Osteoporosis Study. pQCT leg scans were qualitatively graded (1-5) for motion severity. Muscle and motion streak were segmented using semi-automated (watershed) and fully automated (threshold-based) methods, computing area, and density. Binary logistic regression evaluated odds ratios (ORs) for fragility or all-cause fractures related to each of these measures with covariate adjustment. Among the 223 women examined (mean age: 72.7 ± 7.1 years, body mass index: 26.30 ± 4.97 kg/m 2 ), muscle density was significantly lower after removing motion (p < 0.001) for both methods. Motion streak areas segmented using the semi-automated method correlated better with visual motion grades (rho = 0.90, p < 0.01) compared to the fully automated method (rho = 0.65, p < 0.01). Although the analysis-reanalysis precision of motion streak area segmentation using the semi-automated method is above 5% error (6.44%), motion-corrected muscle density measures remained well within 2% analytical error. The effect of motion-correction on strengthening the association between muscle density and fragility fractures was significant when motion grade was ≥3 (p interaction <0.05). This observation was most dramatic for the semi-automated algorithm (OR: 1.62 [0.82,3.17] before to 2.19 [1.05,4.59] after correction). Although muscle density showed an overall association with all-cause fractures (OR: 1.49 [1.05,2.12]), the effect of motion-correction was again, most impactful within individuals with scans showing grade 3 or above motion. Correcting for motion in pQCT leg scans strengthened the relationship between muscle density and fragility fractures, particularly in scans with motion grades of 3 or above. Motion streaks are not confounders to the relationship between pQCT-derived leg muscle density and fractures, but may introduce heterogeneity in muscle density measurements, rendering associations with fractures to be weaker. Copyright © 2016. Published by Elsevier Inc.

Relationship between Quantitative CT Metrics and Health Status and Bode in COPD

PubMed Central

Martinez, Carlos H.; Chen, Ya-Hong; Westgate, Phillip M.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Make, Barry J.; Kazerooni, Ella A.; Lynch, David A.; Marchetti, Nathaniel; Washko, George R.; Martinez, Fernando J.; Han, MeiLan K.

2013-01-01

Background The value of quantitative computed tomography (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. We hypothesized that QCT-defined emphysema and airway abnormalities relate to St. George's Respiratory Questionnaire (SGRQ) and BODE. Methods 1,200 COPDGene subjects meeting GOLD criteria for COPD with QCT analysis were included. Total lung emphysema was measured using density mask technique with a -950 HU threshold. An automated program measured mean wall thickness (WT), wall area percent (WA%) and pi10 in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE. Results In separate models predicting SGRQ score, a one unit standard deviation (SD) increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a one unit SD increase in percent emphysema in these models was relatively weaker, significant only in the pi10 model (for percent emphysema, 1.45 points higher, p=0.01). In separate models predicting BODE, a one unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07 fold increase, p<0.001; for WA%, 1.20 fold increase, p<0.001; for pi10, 1.16 fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26 fold increase, p<0.001). Conclusion Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE. PMID:22514236

Quantitative in vivo assessment of bone microarchitecture in the human knee using HR-pQCT.

PubMed

Kroker, Andres; Zhu, Ying; Manske, Sarah L; Barber, Rhamona; Mohtadi, Nicholas; Boyd, Steven K

2017-04-01

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel imaging modality capable of visualizing bone microarchitecture in vivo at human peripheral sites such as the distal radius and distal tibia. This research has extended the technology to provide a non-invasive assessment of bone microarchitecture at the human knee by establishing new hardware, imaging protocols and data analysis. A custom leg holder was developed to stabilize a human knee centrally within a second generation HR-pQCT field of view. Five participants with anterior cruciate ligament reconstructions had their knee joint imaged in a continuous scan of 6cm axially. The nominal isotropic voxel size was 60.7μm. Bone mineral density and microarchitecture were assessed within the weight-bearing regions of medial and lateral compartments of the knee at three depths from the weight-bearing articular bone surface, including both the cortical and trabecular bone regions. Scan duration was approximately 18min per knee and produced 5GB of projection data and 10GB of reconstructed image data (2304×2304 image matrix, 1008 slices). Motion during the scan was minimized by the leg holder and was similar in magnitude as a scan of the distal tibia. Bone mineral density and microarchitectural parameters were assessed for 16 volumes of interest in the tibiofemoral joint. This is a new non-invasive in vivo assessment tool for bone microarchitecture in the human knee that provides an opportunity to gain insight into normal, injured and surgically reconstructed human knee bone architecture in cross-sectional or longitudinal studies. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Prediction of bone strength at the distal tibia by HR-pQCT and DXA.

PubMed

Popp, Albrecht W; Windolf, Markus; Senn, Christoph; Tami, Andrea; Richards, R Geoff; Brianza, Stefano; Schiuma, Damiano

2012-01-01

Areal bone mineral density (aBMD) at the distal tibia, measured at the epiphysis (T-EPI) and diaphysis (T-DIA), is predictive for fracture risk. Structural bone parameters evaluated at the distal tibia by high resolution peripheral quantitative computed tomography (HR-pQCT) displayed differences between healthy and fracture patients. With its simple geometry, T-DIA may allow investigating the correlation between bone structural parameter and bone strength. Anatomical tibiae were examined ex vivo by DXA (aBMD) and HR-pQCT (volumetric BMD (vBMD) and bone microstructural parameters). Cortical thickness (CTh) and polar moment of inertia (pMOI) were derived from DXA measurements. Finally, an index combining material (BMD) and mechanical property (polar moment of inertia, pMOI) was defined and analyzed for correlation with torque at failure and stiffness values obtained by biomechanical testing. Areal BMD predicted the vBMD at T-EPI and T-DIA. A high correlation was found between aBMD and microstructural parameters at T-EPIas well as between aBMD and CTh at T-DIA. Finally, at T-DIA both indexes combining BMD and pMOI were strongly and comparably correlated with torque at failure and bone stiffness. Ex vivo, at the distal tibial diaphysis, a novel index combining BMD and pMOI, which can be calculated directly from a single DXA measurement, predicted bone strength and stiffness better than either parameter alone and with an order of magnitude comparable to that of HR-pQCT. Whether this index is suitable for better prediction of fracture risk in vivo deserves further investigation. Copyright © 2011 Elsevier Inc. All rights reserved.

Distal radius geometry and skeletal strength indices after peripubertal artistic gymnastics.

PubMed

Dowthwaite, J N; Scerpella, T A

2011-01-01

Development of optimal skeletal strength should decrease adult bone fragility. Nongymnasts (NON): were compared with girls exposed to gymnastics during growth (EX/GYM: ), using peripheral quantitative computed tomography (pQCT) to evaluate postmenarcheal bone geometry, density, and strength. Pre- and perimenarcheal gymnastic loading yields advantages in indices of postmenarcheal bone geometry and skeletal strength. Two prior studies using pQCT have reported bone density and size advantages in Tanner I/II gymnasts, but none describe gymnasts' bone properties later in adolescence. The current study used pQCT to evaluate whether girls exposed to gymnastics during late childhood growth and perimenarcheal growth exhibited greater indices of distal radius geometry, density, and skeletal strength. Postmenarcheal subjects underwent 4% and 33% distal radius pQCT scans, yielding: 1) vBMD and cross-sectional areas (CSA) (total bone, compartments); 2) polar strength-strain index; 3) index of structural strength in axial compression. Output was compared for EX/GYM: vs. NON: , adjusting for gynecological age and stature (maturity and body size), reporting means, standard errors, and significance. Sixteen postmenarcheal EX/GYM: (age 16.7 years; gynecological age 3.4 years) and 13 NON: (age 16.2 years; gynecological age 3.6 years) were evaluated. At both diaphysis and metaphysis, EX/GYM: exhibited greater CSA and bone strength indices than NON; EX/GYM: exhibited 79% larger intramedullary CSA than NON: (p < 0.05). EX/GYM: had significantly higher 4% trabecular vBMD; differences were not detected for 4% total vBMD and 33% cortical vBMD. Following pre-/perimenarcheal gymnastic exposure, relative to nongymnasts, postmenarcheal EX/GYM: demonstrated greater indices of distal radius geometry and skeletal strength (metaphysis and diaphysis) with greater metaphyseal trabecular vBMD; larger intramedullary cavity size was particularly striking.

Distal radius geometry and skeletal strength indices after peripubertal artistic gymnastics

PubMed Central

Scerpella, T. A.

2011-01-01

Summary Development of optimal skeletal strength should decrease adult bone fragility. Nongymnasts (NON) were compared with girls exposed to gymnastics during growth (EX/GYM), using peripheral quantitative computed tomography (pQCT) to evaluate postmenarcheal bone geometry, density, and strength. Pre- and perimenarcheal gymnastic loading yields advantages in indices of postmenarcheal bone geometry and skeletal strength. Introduction Two prior studies using pQCT have reported bone density and size advantages in Tanner I/II gymnasts, but none describe gymnasts’ bone properties later in adolescence. The current study used pQCT to evaluate whether girls exposed to gymnastics during late childhood growth and perimenarcheal growth exhibited greater indices of distal radius geometry, density, and skeletal strength. Methods Postmenarcheal subjects underwent 4% and 33% distal radius pQCT scans, yielding: 1) vBMD and cross-sectional areas (CSA) (total bone, compartments); 2) polar strength-strain index; 3) index of structural strength in axial compression. Output was compared for EX/GYM vs. NON, adjusting for gynecological age and stature (maturity and body size), reporting means, standard errors, and significance. Results Sixteen postmenarcheal EX/GYM (age 16.7 years; gynecological age 3.4 years) and 13 NON (age 16.2 years; gynecological age 3.6 years) were evaluated. At both diaphysis and metaphysis, EX/GYM exhibited greater CSA and bone strength indices than NON; EX/GYM exhibited 79% larger intramedullary CSA than NON (p<0.05). EX/GYM had significantly higher 4% trabecular vBMD; differences were not detected for 4% total vBMD and 33% cortical vBMD. Conclusions Following pre-/perimenarcheal gymnastic exposure, relative to nongymnasts, postmenarcheal EX/GYM demonstrated greater indices of distal radius geometry and skeletal strength (metaphysis and diaphysis) with greater metaphyseal trabecular vBMD; larger intramedullary cavity size was particularly striking. PMID:20419293

Current methods and advances in bone densitometry

NASA Technical Reports Server (NTRS)

Guglielmi, G.; Gluer, C. C.; Majumdar, S.; Blunt, B. A.; Genant, H. K.

1995-01-01

Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.

PubMed

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases.

Pullout strength of monocortical and bicortical screws in metaphyseal and diaphyseal regions of the canine humerus.

PubMed

Vaughn, Denty Paul; Syrcle, Jason Alan; Ball, John E; Elder, Steven H; Gambino, Jennifer Michele; Griffin, Russell L; McLaughlin, Ronald M

2016-11-23

Monocortical screws are commonly employed in locking plate fixation, but specific recommendations for their placement are lacking and use of short monocortical screws in metaphyseal bone may be contraindicated. Objectives of this study were to evaluate axial pullout strength of two different lengths of monocortical screws placed in various regions of the canine humerus compared to bicortical screws, and to derive cortical thickness and bone density values for those regions using quantitative computed tomography analysis (QCT). The QCT analysis was performed on 36 cadaveric canine humeri for six regions of interest (ROI). A bicortical, short monocortical, or 50% transcortical 3.5 mm screw was implanted in each ROI and axial pullout testing was performed. Bicortical screws were stronger than monocortical screws in all ROI except the lateral epicondylar crest. Short monocortical metaphyseal screws were weaker than those placed in other regions. The 50% transcortical screws were stronger than the short monocortical screws in the condyle. A linear relationship between screw length and pullout strength was observed. Cortical thickness and bone density measurements were obtained from multiple regions of the canine humerus using QCT. Use of short monocortical screws may contribute to failure of locking plate fixation of humeral fractures, especially when placed in the condyle. When bicortical screw placement is not possible, maximizing monocortical screw length may optimize fixation stability for distal humeral fractures.

DXA and pQCT predict pertrochanteric and not femoral neck fracture load in a human side-impact fracture model.

PubMed

Gebauer, Matthias; Stark, Olaf; Vettorazzi, Eik; Grifka, Joachim; Püschel, Klaus; Amling, Michael; Beckmann, Johannes

2014-01-01

The validity of dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) measurements as predictors of pertrochanteric and femoral neck fracture loads was compared in an experimental simulation of a fall on the greater trochanter. 65 proximal femora were harvested from patients at autopsy. All specimens were scanned with use of DXA for areal bone mineral density and pQCT for volumetric densities at selected sites of the proximal femur. A three-point bending test simulating a side-impact was performed to determine fracture load and resulted in 16 femoral neck and 49 pertrochanteric fractures. Regression analysis revealed that DXA BMD trochanter was the best variable at predicting fracture load of pertrochanteric fractures with an adjusted R(2) of 0.824 (p < 0.0001). There was no correlation between densitometric parameters and the fracture load of femoral neck fractures. A significant correlation further was found between body weight, height, femoral head diameter, and neck length on the one side and fracture load on the other side, irrespective of the fracture type. Clinically, the DXA BMD trochanter should be favored and integrated routinely as well as biometric and geometric parameters, particularly in elderly people with known osteoporosis at risk for falls. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Modeling of molecular nitrogen collisions and dissociation processes for direct simulation Monte Carlo.

PubMed

Parsons, Neal; Levin, Deborah A; van Duin, Adri C T; Zhu, Tong

2014-12-21

The Direct Simulation Monte Carlo (DSMC) method typically used for simulating hypersonic Earth re-entry flows requires accurate total collision cross sections and reaction probabilities. However, total cross sections are often determined from extrapolations of relatively low-temperature viscosity data, so their reliability is unknown for the high temperatures observed in hypersonic flows. Existing DSMC reaction models accurately reproduce experimental equilibrium reaction rates, but the applicability of these rates to the strong thermal nonequilibrium observed in hypersonic shocks is unknown. For hypersonic flows, these modeling issues are particularly relevant for nitrogen, the dominant species of air. To rectify this deficiency, the Molecular Dynamics/Quasi-Classical Trajectories (MD/QCT) method is used to accurately compute collision and reaction cross sections for the N2(Σg+1)-N2(Σg+1) collision pair for conditions expected in hypersonic shocks using a new potential energy surface developed using a ReaxFF fit to recent advanced ab initio calculations. The MD/QCT-computed reaction probabilities were found to exhibit better physical behavior and predict less dissociation than the baseline total collision energy reaction model for strong nonequilibrium conditions expected in a shock. The MD/QCT reaction model compared well with computed equilibrium reaction rates and shock-tube data. In addition, the MD/QCT-computed total cross sections were found to agree well with established variable hard sphere total cross sections.

Volumetric bone mineral density (vBMD), bone structure, and structural geometry among rural South Indian, US Caucasian, and Afro-Caribbean older men.

PubMed

Jammy, Guru Rajesh; Boudreau, Robert M; Singh, Tushar; Sharma, Pawan Kumar; Ensrud, Kristine; Zmuda, Joseph M; Reddy, P S; Newman, Anne B; Cauley, Jane A

2018-05-22

Peripheral quantitative computed tomography (pQCT) provides biomechanical estimates of bone strength. Rural South Indian men have reduced biomechanical indices of bone strength compared to US Caucasian and Afro-Caribbean men. This suggests an underlying higher risk of osteoporotic fractures and greater future fracture burden among the rural South Indian men. Geographical and racial comparisons of bone mineral density (BMD) have largely focused on DXA measures of areal BMD. In contrast, peripheral quantitative computed tomography (pQCT) measures volumetric BMD (vBMD), bone structural geometry and provides estimates of biomechanical strength. To further understand potential geographical and racial differences in skeletal health, we compared pQCT measures among US Caucasian, Afro-Caribbean, and rural South Indian men. We studied men aged ≥ 60 years enrolled in the Mobility and Independent Living among Elders Study (MILES) in rural south India (N = 245), Osteoporotic Fractures in Men Study (MrOS) in the US (N = 1148), and the Tobago Bone Health Study (N = 828). The BMI (kg/m 2 ) of rural South Indian men (21.6) was significantly lower compared to the US Caucasians (28) and Afro-Caribbean men (26.9). Adjusting for age, height, body weight, and grip strength; rural South Indian men compared to US Caucasians had significantly lower trabecular vBMD [- 1.3 to - 1.5 standard deviation (SD)], cortical thickness [- 0.8 to - 1.2 SD]; significantly higher endosteal circumference [0.5 to 0.8 SD]; but similar cortical vBMD. Afro-Caribbean men compared to US Caucasians had similar trabecular vBMD but significantly higher cortical vBMD [0.9 to 1.2 SD], SSIp [0.2 to 1.4 SD], and tibial endosteal circumference [1 SD], CONCLUSIONS: In comparison to US Caucasians, rural South Indian men have reduced bone strength (lower trabecular vBMD) and Afro-Caribbean men have greater bone strength (higher cortical vBMD). These results suggest an underlying higher risk of osteoporotic fractures and greater future fracture burden among rural South Indian men.

Bone geometry in young male and female football players: a peripheral quantitative computed tomography (pQCT) study.

PubMed

Lozano-Berges, Gabriel; Matute-Llorente, Ángel; Gómez-Bruton, Alejandro; González-Agüero, Alex; Vicente-Rodríguez, Germán; Casajús, José A

2018-05-08

The present study shows that football practice during growth may improve bone geometry in male and female football players. However, only females had better bone strength in comparison with controls. The aim of this study was to compare bone geometry in adolescent football players and controls. A total of 107 football players (71 males/36 females; mean age 12.7 ± 0.6/12.7 ± 0.6 years) and 42 controls (20 males/22 females; mean age 13.1 ± 1.4/12.7 ± 1.3 years) participated in this study. Total and trabecular volumetric bone mineral content (Tt.BMC/Tb.BMC), cross-sectional area (Tt.Ar/Tb.Ar), and bone strength index (BSI) were measured at 4% site of the non-dominant tibia by peripheral quantitative computed tomography (pQCT). Moreover, Tt.BMC, cortical BMC (Ct.BMC), Tt.Ar, cortical Ar (Ct.Ar), cortical thickness (Ct.Th), periosteal circumference (PC), endosteal circumference (EC), fracture load in X-axis, and polar strength strain index (SSIp) were measured at 38% site of the tibia. Multivariate analyses of covariance were used to compare bone pQCT variables between football players and controls using the tibia length and maturity offset as covariates. Female football players demonstrated 13.8-16.4% higher BSI, Ct.Th, fracture load in X-axis, and SSIp than controls (p < .0036). Males showed no significant differences in bone strength when compared to controls (p > .0036). In relation to bone mineral content and area, male football players showed 8.8% higher Tt.Ar and Tb.Ar at the 4% site of the tibia when compared to controls; whereas 13.8-15.8% higher Tt.BMC, Ct.BMC, and Ct.Ar at the 38% site of the tibia were found in female football players than controls (p < .0036). In this study, female adolescent football players presented better bone geometry and strength values than controls. In contrast, only bone geometry was higher in male football players than controls.

The peripheral quantitative computed tomographic and densitometric analysis of skeletal tissue in male Wistar rats after chromium sulfate treatment.

PubMed

Bieńko, Marek; Radzki, Radosław Piotr; Wolski, Dariusz

2017-09-21

This study evaluates the effects of three different doses of chromium sulphate on bone density and the tomographic parameters of skeletal tissue of rats. The experiment was performed on 40 male Wistar rats which received, by gavage, during 90 days, a chromium sulphate in either a daily dose of 400, 600 or 800 µg/kg BW. At the end of experiment, the rats were scanned using the densitometry method (DXA) to determine the bone mineral density, bone mineral content of total skeleton and vertebral column (L2-L4) and parameters of body composition (Lean Mass and Fat Mass). The isolated femora were scanned using peripheral a quantitative computed tomography method (pQCT) for a separate analysis of the trabecular and cortical bone tissue. The ultimate strength, work to ultimate and the Young modulus of femora was also investigated by the three-point bending test. The negative impact of chromium was observed in relation to bone tissue. All doses significantly decreased total skeleton density and mineral content, and also had impact upon the isolated femora and vertebral column. Trabecular volumetric bone mineral density and trabecular bone mineral content measured by pQCT in distal femur metaphysis were significantly lower in the experimental groups than in the control. Higher doses of chromium also significantly decreased values of ultimate strength and Young modulus in the investigated femora. The results of the experiment demonstrate that chromium sulphate is dose dependent, and exerts a disadvantageous effect on the skeleton, as it decreases bone density and resistance.

Vertebral deformities and fractures are associated with MRI and pQCT measures obtained at the distal tibia and radius of postmenopausal women

PubMed Central

Rajapakse, C. S.; Phillips, E. A.; Sun, W.; Wald, M. J.; Magland, J. F.; Snyder, P. J.; Wehrli, F. W.

2016-01-01

Summary We investigated the association of postmenopausal vertebral deformities and fractures with bone parameters derived from distal extremities using MRI and pQCT. Distal extremity measures showed variable degrees of association with vertebral deformities and fractures, highlighting the systemic nature of postmenopausal bone loss. Introduction Prevalent vertebral deformities and fractures are known to predict incident further fractures. However, the association of distal extremity measures and vertebral deformities in postmenopausal women has not been fully established. Methods This study involved 98 postmenopausal women (age range 60–88 years, mean 70 years) with DXA BMD T-scores at either the hip or spine in the range of −1.5 to −3.5. Wedge, biconcavity, and crush deformities were computed on the basis of spine MRI. Vertebral fractures were assessed using Eastell's criterion. Distal tibia and radius stiffness was computed using MRI-based finite element analysis. BMD at the distal extremities were obtained using pQCT. Results Several distal extremity MRI and pQCT measures showed negative association with vertebral deformity on the basis of single parameter correlation (r up to 0.67) and two-parameter regression (r up to 0.76) models involving MRI stiffness and pQCT BMD. Subjects who had at least one prevalent vertebral fracture showed decreased MRI stiffness (up to 17.9 %) and pQCT density (up to 34.2 %) at the distal extremities compared to the non-fracture group. DXA lumbar spine BMD T-score was not associated with vertebral deformities. Conclusions The association between vertebral deformities and distal extremity measures supports the notion of postmenopausal osteoporosis as a systemic phenomenon. PMID:24221453

A Numeric Analysis of Bone Density in the Edentulous Interforaminal Region.

PubMed

Tavitian, Patrick; Ruquet, Michel; Mensé, Chloe; Nicolas, Emmanuel; Hue, Olivier

The purpose of this study was to assess the density of interforaminal bone using quantitative computed tomography (QCT) in simulated case histories to be prescribed an All-on-Five fixed implant treatment protocol. QCT scans from 30 edentulous patients (15 men and 15 women; mean age 63.33 ± 9.3 years) were analyzed using the Nobel Clinician software. Densities (in Hounsfield units [HU]) were recorded at the neck, middle part of the body, and apex of the lingual and buccal parts of proposed implant sites. The highest bone densities were measured at the neck of the implant (1,187 ± 382 HU), with lower densities at the apex (774 ± 571 HU) (P < .01). Bone densities decreased on the lingual interforaminal portion of the implant, especially on the two intermediate implants. Bone density was lower in women (917 ± 510 HU) than in men (1,095 ± 601 HU) (P < .01). The interforaminal measured bone densities are lower on the paramedian region of the symphysis and in women. However, these levels are in accordance with immediate loading with a fixed partial denture.

The effect of variable waveform low-intensity pulsed ultrasound in a fourth metacarpal osteotomy gap model in horses.

PubMed

McClure, S R; Miles, K; Vansickle, D; South, T

2010-08-01

The objective of this study was to evaluate the effects of variable waveform low-intensity ultrasound on the healing of a fracture gap of the fourth metacarpal bone in horses. A randomized, blinded, controlled trial was conducted in eight healthy adult horses. In each horse, a 1-cm osteotomy of the fourth metacarpal bone was created. One randomly selected metacarpal gap was treated daily with a 40-min session of ultrasound and the opposite gap was managed similarly with an inactive transducer. The fourth metacarpal bones were radiographed weekly. Fluorescent markers were administered at 14, 28, 56 and 70 d. At the completion of the study at day 84, the bones were harvested and evaluated with peripheral quantitative computed tomography (pQCT) and histology. There were no significant differences between treated and control bones for any of the radiographic, pQCT or histologic parameters evaluated. These findings suggested that low-intensity ultrasound did not affect bone formation in a fracture gap model in the horse. Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

NASA Technical Reports Server (NTRS)

Allen, Matthew R.; Bloomfield, Susan A.

2003-01-01

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT

PubMed Central

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Summary Introduction Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Methods Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Results Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. Discussion CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases. PMID:28740526

Correlation between degenerative spine disease and bone marrow density: a retrospective investigation.

PubMed

Grams, Astrid Ellen; Rehwald, Rafael; Bartsch, Alexander; Honold, Sarah; Freyschlag, Christian Franz; Knoflach, Michael; Gizewski, Elke Ruth; Glodny, Bernhard

2016-02-24

Spondylosis leads to an overestimation of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) but not with quantitative computed tomography (QCT). The correlation between degenerative changes of the spine and QCT-BMD was therefore investigated for the first time. One hundred thirty-four patients (66 female and 68 male) with a mean age of 49.0 ± 14.6 years (range: 19-88 years) who received a CT scan and QCT-BMD measurements of spine and hip were evaluated retrospectively. The occurrence and severity of spondylosis, osteochondrosis, and spondylarthrosis and the height of the vertebral bodies were assessed. A negative correlation was found between spinal BMD and number of spondylophytes (ρ = -0.35; p < 0.01), disc heights (r = -0.33; p < 0.01), number of discal air inclusions (ρ = -0.34; p < 0.01), the number of Schmorl nodules (ρ = -0.25; p < 0.01), the number (ρ = -0.219; p < 0.05) and the degree (ρ = -0.220; p < 0.05) of spondylarthrosis. Spinal and hip BMD correlated moderately, but the latter did not correlate with degenerative changes of the spine. In linear regression models age, osteochondrosis and spondylarthrosis were factors influencing spinal BMD. Degenerative spinal changes may be associated with reduced regional spinal mineralization. This knowledge could lead to a modification of treatment of degenerative spine disease with early treatment of osteopenia to prevent secondary fractures.

Longitudinal changes in femur bone mineral density after spinal cord injury: effects of slice placement and peel method

PubMed Central

Dudley-Javoroski, S.

2010-01-01

Summary Surveillance of femur metaphysis bone mineral density (BMD) decline after spinal cord injury (SCI) may be subject to slice placement error of 2.5%. Adaptations to anti-osteoporosis measures should exceed this potential source of error. Image analysis parameters likewise affect BMD output and should be selected strategically in longitudinal studies. Introduction Understanding the longitudinal changes in bone mineral density (BMD) after spinal cord injury (SCI) is important when assessing new interventions. We determined the longitudinal effect of SCI on BMD of the femur metaphysis. To facilitate interpretation of longitudinal outcomes, we (1) determined the BMD difference associated with erroneous peripheral quantitative computed tomography (pQCT) slice placement, and (2) determined the effect of operator-selected pQCT peel algorithms on BMD. Methods pQCT images were obtained from the femur metaphysis (12% of length from distal end) of adult subjects with and without SCI. Slice placement errors were simulated at 3 mm intervals and were processed in two ways (threshold-based vs. concentric peel). Results BMD demonstrated a rapid decline over 2 years post-injury. BMD differences attributable to operator-selected peel methods were large (17.3% for subjects with SCI). Conclusions Femur metaphysis BMD declines after SCI in a manner similar to other anatomic sites. Concentric (percentage-based) peel methods may be most appropriate when special sensitivity is required to detect BMD adaptations. Threshold-based methods may be more appropriate when asymmetric adaptations are observed. PMID:19707702

Changes in body composition in triathletes during an Ironman race.

PubMed

Mueller, Sandro Manuel; Anliker, Elmar; Knechtle, Patrizia; Knechtle, Beat; Toigo, Marco

2013-09-01

Triathletes lose body mass during an Ironman triathlon. However, the associated body composition changes remain enigmatic. Thus, the purpose of this study was to investigate Ironman-induced changes in segmental body composition, using for the first time dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Before and after an Ironman triathlon, segmental body composition and lower leg tissue mass, areas and densities were assessed using DXA and pQCT, respectively, in eight non-professional male triathletes. In addition, blood and urine samples were collected for the determination of hydration status. Body mass decreased by 1.9 ± 0.8 kg. This loss was due to 0.4 ± 0.3 and 1.4 ± 0.8 kg decrease in fat and lean mass, respectively (P < 0.01). Calf muscle density was reduced by 1.93 ± 1.04 % (P < 0.01). Hemoglobin, hematocrit, and plasma [K(+)] remained unchanged, while plasma [Na(+)] (P < 0.05), urine specific gravity and plasma and urine osmolality increased (P < 0.01). The loss in lean mass was explained by a decrease in muscle density, as an indicator of glycogen loss, and increases in several indicators for dehydration. The measurement of body composition with DXA and pQCT before and after an Ironman triathlon provided exact values for the loss in fat and lean mass. Consequently, these results yielded more detailed insights into tissue catabolism during ultra-endurance exercise.

In Vivo Precision of Digital Topological Skeletonization Based Individual Trabecula Segmentation (ITS) Analysis of Trabecular Microstructure at the Distal Radius and Tibia by HR-pQCT.

PubMed

Zhou, Bin; Zhang, Zhendong; Wang, Ji; Yu, Y Eric; Liu, Xiaowei Sherry; Nishiyama, Kyle K; Rubin, Mishaela R; Shane, Elizabeth; Bilezikian, John P; Guo, X Edward

2016-06-01

Trabecular plate and rod microstructure plays a dominant role in the apparent mechanical properties of trabecular bone. With high-resolution computed tomography (CT) images, digital topological analysis (DTA) including skeletonization and topological classification was applied to transform the trabecular three-dimensional (3D) network into surface and curve skeletons. Using the DTA-based topological analysis and a new reconstruction/recovery scheme, individual trabecula segmentation (ITS) was developed to segment individual trabecular plates and rods and quantify the trabecular plate- and rod-related morphological parameters. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging technique to visualize 3D bone microstructure. Based on HR-pQCT images, ITS was applied to various HR-pQCT datasets to examine trabecular plate- and rod-related microstructure and has demonstrated great potential in cross-sectional and longitudinal clinical applications. However, the reproducibility of ITS has not been fully determined. The aim of the current study is to quantify the precision errors of ITS plate-rod microstructural parameters. In addition, we utilized three different frequently used contour techniques to separate trabecular and cortical bone and to evaluate their effect on ITS measurements. Overall, good reproducibility was found for the standard HR-pQCT parameters with precision errors for volumetric BMD and bone size between 0.2%-2.0%, and trabecular bone microstructure between 4.9%-6.7% at the radius and tibia. High reproducibility was also achieved for ITS measurements using all three different contour techniques. For example, using automatic contour technology, low precision errors were found for plate and rod trabecular number (pTb.N, rTb.N, 0.9% and 3.6%), plate and rod trabecular thickness (pTb.Th, rTb.Th, 0.6% and 1.7%), plate trabecular surface (pTb.S, 3.4%), rod trabecular length (rTb.ℓ, 0.8%), and plate-plate junction density (P-P Junc.D, 2.3%) at the tibia. The precision errors at the radius were similar to those at the tibia. In addition, precision errors were affected by the contour technique. At the tibia, precision error by the manual contour method was significantly different from automatic and standard contour methods for pTb.N, rTb.N and rTb.Th. Precision error using the manual contour method was also significantly different from the standard contour method for rod trabecular number (rTb.N), rod trabecular thickness (rTb.Th), rod-rod and plate-rod junction densities (R-R Junc.D and P-R Junc.D) at the tibia. At the radius, the precision error was similar between the three different contour methods. Image quality was also found to significantly affect the ITS reproducibility. We concluded that ITS parameters are highly reproducible, giving assurance that future cross-sectional and longitudinal clinical HR-pQCT studies are feasible in the context of limited sample sizes.

Voxel-based modeling and quantification of the proximal femur using inter-subject registration of quantitative CT images.

PubMed

Li, Wenjun; Kezele, Irina; Collins, D Louis; Zijdenbos, Alex; Keyak, Joyce; Kornak, John; Koyama, Alain; Saeed, Isra; Leblanc, Adrian; Harris, Tamara; Lu, Ying; Lang, Thomas

2007-11-01

We have developed a general framework which employs quantitative computed tomography (QCT) imaging and inter-subject image registration to model the three-dimensional structure of the hip, with the goal of quantifying changes in the spatial distribution of bone as it is affected by aging, drug treatment or mechanical unloading. We have adapted rigid and non-rigid inter-subject registration techniques to transform groups of hip QCT scans into a common reference space and to construct composite proximal femoral models. We have applied this technique to a longitudinal study of 16 astronauts who on average, incurred high losses of hip bone density during spaceflights of 4-6 months on the International Space Station (ISS). We compared the pre-flight and post-flight composite hip models, and observed the gradients of the bone loss distribution. We performed paired t-tests, on a voxel by voxel basis, corrected for multiple comparisons using false discovery rate (FDR), and observed regions inside the proximal femur that showed the most significant bone loss. To validate our registration algorithm, we selected the 16 pre-flight scans and manually marked 4 landmarks for each scan. After registration, the average distance between the mapped landmarks and the corresponding landmarks in the target scan was 2.56 mm. The average error due to manual landmark identification was 1.70 mm.

Effect of dexamethasone on mandibular bone biomechanics in rats during the growth phase as assessed by bending test and peripheral quantitative computerized tomography.

PubMed

Bozzini, Clarisa; Champin, Graciela; Alippi, Rosa M; Bozzini, Carlos E

2015-04-01

Long-term glucocorticoid administration to growing rats induces osteopenia and alterations in the biomechanical behavior of the bone. This study was performed to estimate the effects of dexamethasone (DTX), a synthetic steroid with predominant glucocorticoid activity, on the biomechanical properties of the mandible of rats during the growth phase, as assessed by bending test and peripheral quantitative computed tomographic (pQCT) analysis. The data obtained by the two methods will provide more precise information when analyzed together than separately. Female rats aged 23 d (n=7) received 500μg.kg-1 per day of DXT for 4 weeks. At the end of the treatment period, their body weight and body length were 51.3% and 20.6% lower, respectively, than controls. Hemimandible weight and area (an index of mandibular size) were 27.3% and 9.7% lower, respectively. The right hemimandible of each animal was subjected to a mechanical 3-point bending test. Significant weakening of the bone, as shown by a correlative impairment of strength and stiffness, was observed in experimental rats. Bone density and cross-sectional area were measured by pQCT. Cross-sectional, cortical and trabecular areas were reduced by 20% to 30% in the DTX group, as were other cortical parameters, including the bone density, mineral content and cross-sectional moment of inertia. The "bone strength index" (BSI, the product of the pQCT-assessed xCSMI and vCtBMD) was 56% lower in treated rats, which compares well with the 54% and 52% reduction observed in mandibular strength and stiffness determined through the bending test. Data suggest that the corticosteroid exerts a combined, negative action on bone geometry (mass and architecture) and volumetric bone mineral density of cortical bone, which would express independent effects on both cellular (material quality) and tissue (cross-sectional design) levels of biological organization of the skeleton in the species.

Scattered image artifacts from cone beam computed tomography and its clinical potential in bone mineral density estimation.

PubMed

Ko, Hoon; Jeong, Kwanmoon; Lee, Chang-Hoon; Jun, Hong Young; Jeong, Changwon; Lee, Myeung Su; Nam, Yunyoung; Yoon, Kwon-Ha; Lee, Jinseok

2016-01-01

Image artifacts affect the quality of medical images and may obscure anatomic structure and pathology. Numerous methods for suppression and correction of scattered image artifacts have been suggested in the past three decades. In this paper, we assessed the feasibility of use of information on scattered artifacts for estimation of bone mineral density (BMD) without dual-energy X-ray absorptiometry (DXA) or quantitative computed tomographic imaging (QCT). To investigate the relationship between scattered image artifacts and BMD, we first used a forearm phantom and cone-beam computed tomography. In the phantom, we considered two regions of interest-bone-equivalent solid material containing 50 mg HA per cm(-3) and water-to represent low- and high-density trabecular bone, respectively. We compared the scattered image artifacts in the high-density material with those in the low-density material. The technique was then applied to osteoporosis patients and healthy subjects to assess its feasibility for BMD estimation. The high-density material produced a greater number of scattered image artifacts than the low-density material. Moreover, the radius and ulna of healthy subjects produced a greater number of scattered image artifacts than those from osteoporosis patients. Although other parameters, such as bone thickness and X-ray incidence, should be considered, our technique facilitated BMD estimation directly without DXA or QCT. We believe that BMD estimation based on assessment of scattered image artifacts may benefit the prevention, early treatment and management of osteoporosis.

Estimates of volumetric bone density from projectional measurements improve the discriminatory capability of dual X-ray absorptiometry

NASA Technical Reports Server (NTRS)

Jergas, M.; Breitenseher, M.; Gluer, C. C.; Yu, W.; Genant, H. K.

1995-01-01

To determine whether estimates of volumetric bone density from projectional scans of the lumbar spine have weaker associations with height and weight and stronger associations with prevalent vertebral fractures than standard projectional bone mineral density (BMD) and bone mineral content (BMC), we obtained posteroanterior (PA) dual X-ray absorptiometry (DXA), lateral supine DXA (Hologic QDR 2000), and quantitative computed tomography (QCT, GE 9800 scanner) in 260 postmenopausal women enrolled in two trials of treatment for osteoporosis. In 223 women, all vertebral levels, i.e., L2-L4 in the DXA scan and L1-L3 in the QCT scan, could be evaluated. Fifty-five women were diagnosed as having at least one mild fracture (age 67.9 +/- 6.5 years) and 168 women did not have any fractures (age 62.3 +/- 6.9 years). We derived three estimates of "volumetric bone density" from PA DXA (BMAD, BMAD*, and BMD*) and three from paired PA and lateral DXA (WA BMD, WA BMDHol, and eVBMD). While PA BMC and PA BMD were significantly correlated with height (r = 0.49 and r = 0.28) or weight (r = 0.38 and r = 0.37), QCT and the volumetric bone density estimates from paired PA and lateral scans were not (r = -0.083 to r = 0.050). BMAD, BMAD*, and BMD* correlated with weight but not height. The associations with vertebral fracture were stronger for QCT (odds ratio [QR] = 3.17; 95% confidence interval [CI] = 1.90-5.27), eVBMD (OR = 2.87; CI 1.80-4.57), WA BMDHol (OR = 2.86; CI 1.80-4.55) and WA-BMD (OR = 2.77; CI 1.75-4.39) than for BMAD*/BMD* (OR = 2.03; CI 1.32-3.12), BMAD (OR = 1.68; CI 1.14-2.48), lateral BMD (OR = 1.88; CI 1.28-2.77), standard PA BMD (OR = 1.47; CI 1.02-2.13) or PA BMC (OR = 1.22; CI 0.86-1.74). The areas under the receiver operating characteristic (ROC) curves for QCT and all estimates of volumetric BMD were significantly higher compared with standard PA BMD and PA BMC. We conclude that, like QCT, estimates of volumetric bone density from paired PA and lateral scans are unaffected by height and weight and are more strongly associated with vertebral fracture than standard PA BMD or BMC, or estimates of volumetric density that are solely based on PA DXA scans.

Primary Hyperparathyroidism is Associated with Abnormal Cortical and Trabecular Microstructure and Reduced Bone Stiffness in Postmenopausal Women

PubMed Central

Stein, Emily M; Silva, Barbara C; Boutroy, Stephanie; Zhou, Bin; Wang, Ji; Udesky, Julia; Zhang, Chiyuan; McMahon, Donald J; Romano, Megan; Dworakowski, Elzbieta; Costa, Aline G.; Cusano, Natalie; Irani, Dinaz; Cremers, Serge; Shane, Elizabeth; Guo, X Edward; Bilezikian, John P

2013-01-01

Typically, in the milder form of primary hyperparathyroidism (PHPT), seen in most countries now, bone density by DXA and detailed analyses of iliac crest bone biopsies by histomorphometry and µCT show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and non-vertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment. They may help to account for increased global fracture risk in PHPT. PMID:23225022

Mild cognitive impairment is associated with poor physical function but not bone structure or density in late adulthood: findings from the Hertfordshire cohort study.

PubMed

Patel, A; Jameson, K A; Edwards, M H; Ward, K; Gale, C R; Cooper, C; Dennison, Elaine M

2018-04-24

This study investigated the association between mild cognitive impairment (MCI) and physical function and bone health in older adults. MCI was associated with poor physical performance but not bone mineral density or bone microarchitecture. Cross-sectional study to investigate the association between mild cognitive impairment (MCI) and physical performance, and bone health, in a community-dwelling cohort of older adults. Cognitive function of 222 men and 221 women (mean age 75.5 and 75.8 years in men and women, respectively) was assessed by the Strawbridge questionnaire and Mini Mental State Exam (MMSE). Participants underwent dual-energy X-ray absorptiometry (DXA), peripheral-quantitative computed tomography (pQCT) and high-resolution peripheral-quantitative computed tomography (HR-pQCT) scans to assess their bone density, strength and microarchitecture. Their physical function was assessed and a physical performance (PP) score was recorded. In the study, 11.8% of women and 8.1% of men were cognitively impaired on the MMSE (score < 24). On the Strawbridge questionnaire, 24% of women were deemed cognitively impaired compared to 22.3% of men. Cognitive impairment on the Strawbridge questionnaire was associated with poorer physical performance score in men but not in women in the unadjusted analysis. MMSE < 24 was strongly associated with the risk of low physical performance in men (OR 12.9, 95% CI 1.67, 99.8, p = 0.01). Higher MMSE score was associated with better physical performance in both sexes. Poorer cognitive function, whether assessed by the Strawbridge questionnaire, or by MMSE score, was not associated with bone density, shape or microarchitecture, in either sex. MCI in older adults was associated with poor physical performance, but not bone density, shape or microarchitecture.

Correlates of Trabecular and Cortical Volumetric Bone Mineral Density of the Radius and Tibia in Older Men: The Osteoporotic Fractures in Men Study

PubMed Central

Barbour, Kamil E; Zmuda, Joseph M; Strotmeyer, Elsa S; Horwitz, Mara J; Boudreau, Robert; Evans, Rhobert W; Ensrud, Kristine E; Petit, Moira A; Gordon, Christopher L; Cauley, Jane A

2010-01-01

Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research. PMID:20200975

Cross-calibration of liquid and solid QCT calibration standards: corrections to the UCSF normative data

NASA Technical Reports Server (NTRS)

Faulkner, K. G.; Gluer, C. C.; Grampp, S.; Genant, H. K.

1993-01-01

Quantitative computed tomography (QCT) has been shown to be a precise and sensitive method for evaluating spinal bone mineral density (BMD) and skeletal response to aging and therapy. Precise and accurate determination of BMD using QCT requires a calibration standard to compensate for and reduce the effects of beam-hardening artifacts and scanner drift. The first standards were based on dipotassium hydrogen phosphate (K2HPO4) solutions. Recently, several manufacturers have developed stable solid calibration standards based on calcium hydroxyapatite (CHA) in water-equivalent plastic. Due to differences in attenuating properties of the liquid and solid standards, the calibrated BMD values obtained with each system do not agree. In order to compare and interpret the results obtained on both systems, cross-calibration measurements were performed in phantoms and patients using the University of California San Francisco (UCSF) liquid standard and the Image Analysis (IA) solid standard on the UCSF GE 9800 CT scanner. From the phantom measurements, a highly linear relationship was found between the liquid- and solid-calibrated BMD values. No influence on the cross-calibration due to simulated variations in body size or vertebral fat content was seen, though a significant difference in the cross-calibration was observed between scans acquired at 80 and 140 kVp. From the patient measurements, a linear relationship between the liquid (UCSF) and solid (IA) calibrated values was derived for GE 9800 CT scanners at 80 kVp (IA = [1.15 x UCSF] - 7.32).(ABSTRACT TRUNCATED AT 250 WORDS).

Phantom-less bone mineral density (BMD) measurement using dual energy computed tomography-based 3-material decomposition

NASA Astrophysics Data System (ADS)

Hofmann, Philipp; Sedlmair, Martin; Krauss, Bernhard; Wichmann, Julian L.; Bauer, Ralf W.; Flohr, Thomas G.; Mahnken, Andreas H.

2016-03-01

Osteoporosis is a degenerative bone disease usually diagnosed at the manifestation of fragility fractures, which severely endanger the health of especially the elderly. To ensure timely therapeutic countermeasures, noninvasive and widely applicable diagnostic methods are required. Currently the primary quantifiable indicator for bone stability, bone mineral density (BMD), is obtained either by DEXA (Dual-energy X-ray absorptiometry) or qCT (quantitative CT). Both have respective advantages and disadvantages, with DEXA being considered as gold standard. For timely diagnosis of osteoporosis, another CT-based method is presented. A Dual Energy CT reconstruction workflow is being developed to evaluate BMD by evaluating lumbar spine (L1-L4) DE-CT images. The workflow is ROI-based and automated for practical use. A dual energy 3-material decomposition algorithm is used to differentiate bone from soft tissue and fat attenuation. The algorithm uses material attenuation coefficients on different beam energy levels. The bone fraction of the three different tissues is used to calculate the amount of hydroxylapatite in the trabecular bone of the corpus vertebrae inside a predefined ROI. Calibrations have been performed to obtain volumetric bone mineral density (vBMD) without having to add a calibration phantom or to use special scan protocols or hardware. Accuracy and precision are dependent on image noise and comparable to qCT images. Clinical indications are in accordance with the DEXA gold standard. The decomposition-based workflow shows bone degradation effects normally not visible on standard CT images which would induce errors in normal qCT results.

The relationship between legal status, perceived pressure and motivation in treatment for drug dependence: results from a European study of Quasi-Compulsory Treatment.

PubMed

Stevens, Alex; Berto, Daniele; Frick, Ulrich; Hunt, Neil; Kerschl, Viktoria; McSweeney, Tim; Oeuvray, Kerrie; Puppo, Irene; Santa Maria, Alberto; Schaaf, Susanne; Trinkl, Barbara; Uchtenhagen, Ambros; Werdenich, Wolfgang

2006-01-01

This paper reports on intake data from Quasi-Compulsory Treatment in Europe, a study of quasi-compulsory treatment (QCT) for drug dependent offenders. It explores the link between formal legal coercion, perceived pressure to be in treatment and motivation amongst a sample of 845 people who entered treatment for drug dependence in five European countries, half of them in quasi-compulsory treatment and half 'voluntarily'. Using both quantitative and qualitative data, it suggests that those who enter treatment under QCT do perceive greater pressure to be in treatment, but that this does not necessarily lead to higher or lower motivation than 'volunteers'. Many drug-dependent offenders value QCT as an opportunity to get treatment. Motivation is mutable and can be developed or diminished by the quality of support and services offered to drug-dependent offenders.

Antimicrobial Testing Methods & Procedures: MB-31

EPA Pesticide Factsheets

Information about ATMP - SOP Quantitative Disk Carrier Test Method (QCT-2) Modified for Testing Antimicrobial Products Against Spores of Clostridium difficile (ATCC 43598) on Inanimate, Hard, Non-porous Surfaces - MB-31-Final

Effect of Low Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized Placebo Controlled Trial

PubMed Central

Leonard, Mary B.; Shults, Justine; Long, Jin; Baldassano, Robert N.; Brown, J. Keenan; Hommel, Kevin; Zemel, Babette S.; Mahboubi, Soroosh; Whitehead, Krista Howard; Herskovitz, Rita; Lee, Dale; Rausch, Joseph; Rubin, Clinton T.

2016-01-01

Pediatric Crohn's Disease (CD) is associated with low trabecular bone mineral density (BMD), cortical area, and muscle mass. Low magnitude mechanical stimulation (LMMS) may be anabolic. We conducted a 12 month randomized double-blind placebo-controlled trial of 10 minutes daily exposure to LMMS (30 Hz frequency, 0.3 g peak to peak acceleration). The primary outcomes were tibia trabecular BMD and cortical area by peripheral quantitative CT (pQCT) and vertebral trabecular BMD by QCT; additional outcomes included DXA whole body, hip and spine BMD, and leg lean mass. Results were expressed as sex-specific Z-scores relative to age. CD participants, ages 8-21 years with tibia trabecular BMD < 25th percentile for age were eligible and received daily cholecalciferol (800 IU) and calcium (1,000 mg). In total, 138 enrolled (48% male) and 121 (61 active, 60 placebo) completed the 12-month trial. Median adherence measured with an electronic monitor was 79% and did not differ between arms. By intention-to-treat analysis, LMMS had no significant effect on pQCT or DXA outcomes. The mean change in spine QCT trabecular BMD Z-score was +0.22 in the active arm and −0.02 in the placebo arm [difference in change 0.24 (95% CI 0.04, 0.44); p=0.02]. Among those with > 50% adherence, the effect was 0.38 (0.17, 0.58, p<0.0005). Within the active arm, each 10% greater adherence was associated with a 0.06 (0.01, 1.17, p=0.03) greater increase in spine QCT BMD Z-score. Treatment response did not vary according to baseline BMI Z-score, pubertal status, CD severity, or concurrent glucocorticoid or biologic medications. In all participants combined, height, pQCT trabecular BMD and cortical area and DXA outcomes improved significantly. In conclusion, LMMS was associated with increases in vertebral trabecular BMD by QCT; however, no effects were observed at DXA or pQCT sites. PMID:26821779

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

PubMed

Kawalilak, C E; Johnston, J D; Cooper, D M L; Olszynski, W P; Kontulainen, S A

2016-02-01

Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.

Quantitative imaging methods in osteoporosis.

PubMed

Oei, Ling; Koromani, Fjorda; Rivadeneira, Fernando; Zillikens, M Carola; Oei, Edwin H G

2016-12-01

Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray absorptiometry (DXA) are among the strongest known predictors of future osteoporotic fractures. Therefore, current clinical decision making relies heavily on accurate assessment of these imaging features. Further, novel quantitative techniques are being developed to appraise additional characteristics of osteoporosis including three-dimensional bone architecture with quantitative computed tomography (QCT). Dedicated high-resolution (HR) CT equipment is available to enhance image quality. At the other end of the spectrum, by utilizing post-processing techniques such as the trabecular bone score (TBS) information on three-dimensional architecture can be derived from DXA images. Further developments in magnetic resonance imaging (MRI) seem promising to not only capture bone micro-architecture but also characterize processes at the molecular level. This review provides an overview of various quantitative imaging techniques based on different radiological modalities utilized in clinical osteoporosis care and research.

Antimicrobial Testing Methods & Procedures: MB-31-03

EPA Pesticide Factsheets

Information about ATMP - SOP Quantitative Disk Carrier Test Method (QCT-2) Modified for Testing Antimicrobial Products Against Spores of Clostridium difficile (ATCC 43598) on Inanimate, Hard, Non-porous Surfaces - MB-31-03

Ab initio state-specific N2 + O dissociation and exchange modeling for molecular simulations

NASA Astrophysics Data System (ADS)

Luo, Han; Kulakhmetov, Marat; Alexeenko, Alina

2017-02-01

Quasi-classical trajectory (QCT) calculations are used in this work to calculate state-specific N2(X1Σ ) +O(3P ) →2 N(4S ) +O(3P ) dissociation and N2(X1Σ ) +O(3P ) →NO(X2Π ) +N(4S ) exchange cross sections and rates based on the 13A″ and 13A' ab initio potential energy surface by Gamallo et al. [J. Chem. Phys. 119, 2545-2556 (2003)]. The calculations consider translational energies up to 23 eV and temperatures between 1000 K and 20 000 K. Vibrational favoring is observed for dissociation reaction at the whole range of collision energies and for exchange reaction around the dissociation limit. For the same collision energy, cross sections for v = 30 are 4 to 6 times larger than those for the ground state. The exchange reaction has an effective activation energy that is dependent on the initial rovibrational level, which is different from dissociation reaction. In addition, the exchange cross sections have a maximum when the total collision energy (TCE) approaches dissociation energy. The calculations are used to generate compact QCT-derived state-specific dissociation (QCT-SSD) and QCT-derived state-specific exchange (QCT-SSE) models, which describe over 1 × 106 cross sections with about 150 model parameters. The models can be used directly within direct simulation Monte Carlo and computational fluid dynamics simulations. Rate constants predicted by the new models are compared to the experimental measurements, direct QCT calculations and predictions by other models that include: TCE model, Bose-Candler QCT-based exchange model, Macheret-Fridman dissociation model, Macheret's exchange model, and Park's two-temperature model. The new models match QCT-calculated and experimental rates within 30% under nonequilibrium conditions while other models under predict by over an order of magnitude under vibrationally-cold conditions.

Spinal Bone Texture Assessed by Trabecular Bone Score in Adolescent Girls With Anorexia Nervosa

PubMed Central

Donaldson, Abigail A.; Feldman, Henry A.; O'Donnell, Jennifer M.; Gopalakrishnan, Geetha

2015-01-01

Context: Trabecular bone score (TBS) is a bone assessment tool that offers information beyond that afforded by dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) measurements. Adolescents with anorexia nervosa (AN) are known to exhibit compromised bone density and skeletal strength. Objectives: This study aimed to determine TBS among adolescents with AN and evaluate the correlation with anthropometric, clinical and densitometric variables. Design: Areal BMD spinal measures were analyzed for TBS. Findings were compared with clinical (height, weight, body mass index [BMI], age, pubertal development, 25-hydroxyvitamin D) and self-reported data (illness duration, amenorrhea, exercise, fracture, family history of osteoporosis, and antidepressant use), and BMD measures by DXA and peripheral quantitative computed tomography (pQCT). Setting and Participants: This was an urban adolescent program consisting of 57 females with AN, age 11–18 y. Interventions: Interventions included DXA (absolute BMD and Z-score), pQCT (volumetric BMD [vBMD] and stress-strain index [SSI]), laboratory evaluation, and questionnaire administration. Main Outcome Measures: Main outcome measures included TBS, areal and vBMD, SSI, fracture history, disease duration. Results: The TBS of six participants (11%) showed degraded and 19 (33%) partially degraded microarchitecture. Spinal TBS was correlated (P < .05) with age, height, weight, BMI, pubertal stage, BMD, and body composition by DXA, and BMD and SSI by pQCT. TBS was not correlated with disease duration, fracture, vitamin D status, race, or ethnicity, and self-reported health data. Conclusions: TBS showed evidence of degraded microarchitecture in over 40% of this study sample, and strongly correlated with anthropometric data and measures of BMD and skeletal strength. TBS is a novel tool that captures another dimension of bone health in adolescents with AN. PMID:26108094

Development of three-dimensional prints of arthritic joints for supporting patients' awareness to structural damage.

PubMed

Kleyer, Arnd; Beyer, Laura; Simon, Christoph; Stemmler, Fabian; Englbrecht, Matthias; Beyer, Christian; Rech, Jürgen; Manger, Bernhard; Krönke, Gerhard; Schett, Georg; Hueber, Axel J

2017-02-10

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) result in severe joint destruction and functional disability if left untreated. We aim to develop tools that help patients with RA and PsA to understand and experience the impact of inflammatory joint disease on the integrity of their (juxta-articular) bone and increase adherence to medical treatment. In this study, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop 3D prototypes of patients' finger joints. HR-pQCT (XtremeCT, Scanco) measurements were performed in healthy individuals and patients with inflammatory joint disease, followed by a 3D print using the objet30 printer. Healthy participants (n = 10), and patients (n = 15 with RA and 15 with PsA) underwent a detailed, standardized interview with demonstration of printed joints. Utilizing HR-pQCT images of metacarpophalangeal (MCP) heads, high quality and exact 3D prints as prototypes were created. Erosions in different sizes and the trabecular network printed in detail were visualized, demonstrating structural reduction in arthritic vs. healthy bone. After demonstration of 3D prints (healthy vs. erosive joint, visual and haptic) 26/39 (66%) participants (including healthy volunteers) were deeply affected, often quoting "shock". Of the patients with RA and PsA, 13/15 (86%) and 11/15 (73%), respectively, stated that they would rethink their attitude to medication adherence. More importantly, 21/24 patients with RA or PsA (87.5%) expressed that they would have wished to see such 3D prints during their first disease-specific conversations. Using arthro-haptic 3D printed prototypes of joints may help to better understand the impact of inflammatory arthritides on bone integrity and long-term damage.

Lateral Cortical Thickening and Bone Heterogeneity of the Subtrochanteric Femur Measured With Quantitative CT as Indicators for Early Detection of Atypical Femoral Fractures in Long-Term Bisphosphonate Users.

PubMed

Lee, Seung Hyun; Lee, Young Han; Suh, Jin-Suck

2017-10-01

The objective of our study was to compare subtrochanteric femur bone mineral density (BMD) and bone quality of long-term bisphosphonate (BP) users who sustained an atypical femoral fracture (AFF) with BP users who did not sustain a femoral fracture and BP-naïve patients with no history of femoral fracture using quantitative CT (QCT). Fourteen female BP users with an AFF (mean age, 72.6 years; mean duration of BP use, 6.2 years; mean body mass index, 21.9) who had undergone QCT before fracture events were sex-, age-, BP use duration-, and body mass index-matched to 14 BP users who did not sustain a fracture and 14 BP-naïve patients. The lateral cortical thickness index (CTI) and the mean BMD (BMD mean ) and SD of the BMD (BMD SD ) within the lateral cortex and within the entire cross-sectional area of the subtrochanteric femur were measured on axial QCT. Femoral neck-shaft angles were measured on the QCT scout image. Parameters were analyzed using the Kruskal-Wallis test. Lateral CTIs were greater in the BP users with an AFF (median, 0.28) than in the BP users without a femoral fracture (median, 0.21) (p = 0.038) and the BP-naïve group (median, 0.21) (p = 0.009). The lateral cortex BMD SD was significantly higher in the BP users with an AFF (median, 59.59 mg/cm 3 ) than the BP users without a femoral fracture (median, 39.27 mg/cm 3 ; p = 0.049) and the BP-naïve group (median, 31.02 mg/cm 3 ; p = 0.037). There was no significant difference among groups in lateral cortex BMD mean , BMD mean and BMD SD of the entire cross-sectional area, and femoral neck-shaft angle. Long-term BP users with a subsequent AFF had a thicker lateral cortex and higher lateral cortex BMD SD at the subtrochanteric area before the fracture on QCT than BP users who did not sustain a femoral fracture and BP-naïve patients.

Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta.

PubMed

Kocijan, R; Muschitz, C; Haschka, J; Hans, D; Nia, A; Geroldinger, A; Ardelt, M; Wakolbinger, R; Resch, H

2015-10-01

Bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) was assessed in adult patients with mild, moderate, and severe osteogenesis imperfecta (OI). The trabecular bone score (TBS), bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and dual X-ray and laser (DXL) at the calcaneus were likewise assessed in patients with OI. Trabecular microstructure and BMD in particular were severely altered in patients with OI. OI is characterized by high fracture risk but not necessarily by low BMD. The main purpose of this study was to assess bone microarchitecture and BMD at different skeletal sites in different types of OI. HR-pQCT was performed in 30 patients with OI (mild OI-I, n = 18 (41.8 [34.7, 55.7] years) and moderate to severe OI-III-IV, n = 12 (47.6 [35.3, 58.4] years)) and 30 healthy age-matched controls. TBS, BMD by DXA at the lumbar spine and hip, as well as BMD by DXL at the calcaneus were likewise assessed in patients with OI only. At the radius, significantly lower trabecular parameters including BV/TV (p = 0.01 and p < 0.0001, respectively) and trabecular number (p < 0.0001 and p < 0.0001, respectively) as well as an increased inhomogeneity of the trabecular network (p < 0.0001 and p < 0.0001, respectively) were observed in OI-I and OI-III-IV in comparison to the control group. Similar results for trabecular parameters were found at the tibia. Microstructural parameters were worse in OI-III-IV than in OI-I. No significant differences were found in cortical thickness and cortical porosity between the three subgroups at the radius. The cortical thickness of the tibia was thinner in OI-I (p < 0.001), but not OI-III-IV, when compared to controls. Trabecular BMD and trabecular bone microstructure in particular are severely altered in patients with clinical OI-I and OI-III-IV. Low TBS and DXL and their significant associations to HR-pQCT parameters of trabecular bone support this conclusion.

Scaling Atomic Partial Charges of Carbonate Solvents for Lithium Ion Solvation and Diffusion

DOE PAGES

Chaudhari, Mangesh I.; Nair, Jijeesh R.; Pratt, Lawrence R.; ...

2016-10-21

Lithium-ion solvation and diffusion properties in ethylene carbonate (EC) and propylene carbonate (PC) were studied by molecular simulation, experiments, and electronic structure calculations. Studies carried out in water provide a reference for interpretation. Classical molecular dynamics simulation results are compared to ab initio molecular dynamics to assess nonpolarizable force field parameters for solvation structure of the carbonate solvents. Quasi-chemical theory (QCT) was adapted to take advantage of fourfold occupancy of the near-neighbor solvation structure observed in simulations and used to calculate solvation free energies. The computed free energy for transfer of Li + to PC from water, based on electronicmore » structure calculations with cluster-QCT, agrees with the experimental value. The simulation-based direct-QCT results with scaled partial charges agree with the electronic structure-based QCT values. The computed Li +/PF 6 - transference numbers of 0.35/0.65 (EC) and 0.31/0.69 (PC) agree well with NMR experimental values of 0.31/0.69 (EC) and 0.34/0.66 (PC) and similar values obtained here with impedance spectroscopy. These combined results demonstrate that solvent partial charges can be scaled in systems dominated by strong electrostatic interactions to achieve trends in ion solvation and transport properties that are comparable to ab initio and experimental results. Thus, the results support the use of scaled partial charges in simple, nonpolarizable force fields in future studies of these electrolyte solutions.« less

Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the NASA Bone Summit.

PubMed

Orwoll, Eric S; Adler, Robert A; Amin, Shreyasee; Binkley, Neil; Lewiecki, E Michael; Petak, Steven M; Shapses, Sue A; Sinaki, Mehrsheed; Watts, Nelson B; Sibonga, Jean D

2013-06-01

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions. Copyright © 2013 American Society for Bone and Mineral Research.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

PubMed

Brady, R D; Grills, B L; Romano, T; Wark, J D; O'Brien, T J; Shultz, S R; McDonald, S J

2016-12-14

Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Bone Status Among Patients With Nonsurgical Hypoparathyroidism, Autosomal Dominant Hypocalcaemia, and Pseudohypoparathyroidism: A Cohort Study.

PubMed

Underbjerg, Line; Malmstroem, Sofie; Sikjaer, Tanja; Rejnmark, Lars

2018-03-01

Nonsurgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP) are both rare diseases, characterized by hypocalcemia. In Ns-HypoPT, PTH levels are low, whereas patients with PHP often have very high levels due to receptor-insensitivity to PTH (PTH-resistance). Accordingly, we hypothesized that indices of bone turnover and bone mineralization/architecture are similar in Ns-HypoPT and PHP despite marked differences in PTH levels. We studied 62 patients with Ns-HypoPT and 31 with PHP as well as a group of age- and sex-matched healthy controls. We found a significantly higher areal BMD (aBMD) by DXA among patients with Ns-HypoPT, both compared with PHP and the background population. Compared with Ns-HypoPT, PHP patients had significantly lower total and trabecular volumetric BMD (vBMD) assessed by quantitative computed tomography (QCT) scans at the spine and hip. High-resolution peripheral quantitative computed tomography (HRpQCT) scans showed a lower trabecular area and vBMD as well as a lower trabecular number at the tibia in PHP compared to Ns-HypoPT and matched controls. In PHP, PTH levels correlated with levels of markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, P1NP), and bone resorption (CTx). In adult males, levels of bone markers were significantly higher in PHP compared with Ns-HypoPT. Levels of procalcitonin and calcitonin were significantly higher in PHP compared with Ns-HypoPT. In conclusion, indices of bone turnover, density, and microarchitecture differ between patients with Ns-HypoPT and PHP. Our data suggest that patients with PHP do not have a complete skeletal resistance to PTH and that the effects of chronically high PTH levels in PHP are mostly confined to the trabecular tissue. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

PubMed Central

2015-01-01

Background Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use. Research Design and Methods A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects. Results A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs. Conclusion The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance may indirectly suggest that patients with T2DM have deteriorated bone material compared with nondiabetic subjects, a potential cause of bone fragility in T2DM patients. PMID:26642210

Noninvasive imaging of bone microarchitecture

PubMed Central

Patsch, Janina M.; Burghardt, Andrew J.; Kazakia, Galateia; Majumdar, Sharmila

2015-01-01

The noninvasive quantification of peripheral compartment-specific bone microarchitecture is feasible with high-resolution peripheral quantitative computed tomography (HR-pQCT) and high-resolution magnetic resonance imaging (HR-MRI). In addition to classic morphometric indices, both techniques provide a suitable basis for virtual biomechanical testing using finite element (FE) analyses. Methodical limitations, morphometric parameter definition, and motion artifacts have to be considered to achieve optimal data interpretation from imaging studies. With increasing availability of in vivo high-resolution bone imaging techniques, special emphasis should be put on quality control including multicenter, cross-site validations. Importantly, conclusions from interventional studies investigating the effects of antiosteoporotic drugs on bone microarchitecture should be drawn with care, ideally involving imaging scientists, translational researchers, and clinicians. PMID:22172043

Enhancement of physico-chemical properties of the hydrophobic anticancer molecule following nanoencapsulation

NASA Astrophysics Data System (ADS)

Kumari, Anshu; Kumar, Amit; Gupta, Sharad

2018-02-01

Flavonoids are one of the important naturally available small molecules found in our daily diets. They have been considered as potential therapeutic agents for anticancer therapy. Despite their anti-cancer properties, their therapeutic application is very limited due to poor water solubility, which results in poor bioavailability to the diseased cells. Hence, to overcome this limitation of Flavonoids, Quercetin (Qct), the most extensively studied flavonoid, prompted us to encapsulate it within nanoparticles. We have successfully encapsulated Qct within cationic polymer based nanoparticles using simple two-step self-assembly fabrication method and studied its effect on absorption and emission properties of Qct. This study was aimed at Qct encapsulation and its effect on the optical properties of Qct for the diagnostic applications. Our results indicate that Qct was efficiently encapsulated within the polymeric nanoparticles. This resulted into 17 times increase in fluorescence emission of encapsulated Qct (Qct-NPs) in comparison with its aqueous suspension. Thus, Qct-NPs can be utilized as a fluorescent probe for various biomedical applications. These probes will have multiple functions integrated into a single nanostructure, enabling the Qct nanoparticles for imaging and therapy. This is the first report on the effect of nanoencapsulation on optical properties of Qct. Thus, Qct-NPs can be harnessed as an effective theranostic agent, and that will not only allow to image and but also treat the cancer in a single clinical procedure.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk

PubMed Central

Jaramillo, Joshua D.; Wilson, Carla; Stinson, Douglas J.; Lynch, David A.; Bowler, Russell P.; Lutz, Sharon; Bon, Jessica M.; Arnold, Ben; McDonald, Merry-Lynn N.; Washko, George R.; Wan, Emily S.; DeMeo, Dawn L.; Foreman, Marilyn G.; Soler, Xavier; Lindsay, Sarah E.; Lane, Nancy E.; Genant, Harry K.; Silverman, Edwin K.; Hokanson, John E.; Make, Barry J.; Crapo, James D.

2015-01-01

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. Methods: Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use. Measurements and Main Results: vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures. Conclusions: Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population. PMID:25719895

Trabecular bone microstructure is impaired in the proximal femur of human immunodeficiency virus-infected men with normal bone mineral density.

PubMed

Kazakia, Galateia J; Carballido-Gamio, Julio; Lai, Andrew; Nardo, Lorenzo; Facchetti, Luca; Pasco, Courtney; Zhang, Chiyuan A; Han, Misung; Parrott, Amanda Hutton; Tien, Phyllis; Krug, Roland

2018-02-01

There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis. Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA. Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV-infected patients and healthy controls. Our results suggest that high-resolution imaging is a powerful tool to assess trabecular bone microstructure and can be used to assess bone health in HIV-infected men who show no differences to healthy males by DXA aBMD. Advances in MRI technology have made microstructural imaging at the proximal femur possible. Further studies in larger patient cohorts are clearly warranted.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

PubMed

Jaramillo, Joshua D; Wilson, Carla; Stinson, Douglas S; Stinson, Douglas J; Lynch, David A; Bowler, Russell P; Lutz, Sharon; Bon, Jessica M; Arnold, Ben; McDonald, Merry-Lynn N; Washko, George R; Wan, Emily S; DeMeo, Dawn L; Foreman, Marilyn G; Soler, Xavier; Lindsay, Sarah E; Lane, Nancy E; Genant, Harry K; Silverman, Edwin K; Hokanson, John E; Make, Barry J; Crapo, James D; Regan, Elizabeth A

2015-05-01

Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use. vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures. Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.

Asymptomatic Kidney Stones in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

PubMed Central

Thomas, Nicole A.; Rai, Shesh N.; Cheon, Kyeongmi; McCammon, Elizabeth; Chesney, Russell; Jones, Deborah; Pui, Ching-Hon; Hudson, Melissa M.

2009-01-01

We hypothesized an association between renal calculi and bone mineral density (BMD) deficits, shown in adults, exists in survivors of childhood ALL. Thus, we analyzed associations between quantitative computed tomography (QCT)-determined renal calcifications and clinical parameters (gender, race, age at diagnosis, age at time of QCT), BMD, treatment exposures, Tanner stage. We investigated associations between stone formation and nutritional intake, serum and urinary calcium and creatinine levels, and urinary calcium/creatinine ratio. Exact Chi-square test was used to compare categorical patient characteristics and Wilcoxon-Mann-Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%) were male; 371 (87.5%) were non-black. Most (n=270; 63.7%) were ≥ 3.5 years at ALL diagnosis. Mean (SD) and median (range) BMD Z-scores of the entire cohort was -0.4 (1.2) and -0.5 (-3.9 to 5.1), respectively. Nineteen (10 males; 10 Caucasians) had kidney stones (observed prevalence of 4.5 %; 19/424) with significant negative association between stone formation and body habitus (BMI, p=0.003). Stone formation was associated with treatment protocol (p=0.009) and treatment group (0.007). Thus, kidney stones in childhood ALL survivors could herald future deterioration of renal function and development of hypertension. Long-term follow-up imaging may be warranted in these patients to monitor for progressive morbidity. PMID:18830261

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

PubMed

Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene; Mosekilde, Leif; Rejnmark, Lars

2015-09-01

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sex differences in parameters of bone strength in new recruits: beyond bone density.

PubMed

Evans, Rachel K; Negus, Charles; Antczak, Amanda J; Yanovich, Ran; Israeli, Eran; Moran, Daniel S

2008-11-01

Stress fracture (SF) injuries in new recruits have long been attributed to low bone mineral density (BMD). Low areal BMD assessed using two-dimensional dual-energy x-ray absorptiometry imaging, however, reflects structural density and is affected by smaller measures of bone geometry. Recent studies support a relationship between bone size and SF and indicate that slender bones are more susceptible to damage under identical loading conditions. Peripheral quantitative computed tomography (pQCT) is a three-dimensional imaging tool that provides measures of tissue density and geometry parameters of the tibia, a common site of SF. To evaluate sex differences in parameters of volumetric BMD (vBMD), geometry, and strength of the tibia in new recruits using a novel pQCT image analysis procedure. pQCT images were obtained from 128 healthy men and women (20 male, 108 female, aged 18-21 yr) entering a 4-month gender-integrated combat training program in the Israeli Defense Forces. Tibial scans taken at sites 4% (trabecular bone), 38%, and 66% (cortical bone) from the distal end plate were analyzed using MATLAB to assess whole-bone and regional parameters. Measures included vBMD, geometry (diameter, area, cortical thickness, and canal radius), and strength (moments of inertia and bone strength and slenderness indices). With the exception of normalized canal radius, which did not differ between sexes, all measures of bone geometry (P < 0.0001) and strength (P < 0.0001 to P = 0.07) were greater in men. Women exhibited 2.7% to 3.0% greater cortical vBMD than men, whereas trabecular vBMD was 8.4% lower in women (P < 0.001). These differences remained significant after adjusting for body size. Sex differences in bone geometry and mineralization of the tibia may contribute to a decreased ability to withstand the demands imposed by novel, repetitive exercise in untrained individuals entering recruit training.

Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD.

PubMed

Okazaki, Narihiro; Burghardt, Andrew J; Chiba, Ko; Schafer, Anne L; Majumdar, Sharmila

2016-12-01

The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD). Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA). Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia ( r  = 0.36, p  = 0.001, and r  = 0.47, p  < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone. Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.

Quantitative CT Measures of Bronchiectasis in Smokers.

PubMed

Diaz, Alejandro A; Young, Thomas P; Maselli, Diego J; Martinez, Carlos H; Gill, Ritu; Nardelli, Pietro; Wang, Wei; Kinney, Gregory L; Hokanson, John E; Washko, George R; San Jose Estepar, Raul

2017-06-01

Bronchiectasis is frequent in smokers with COPD; however, there are only limited data on objective assessments of this process. The objective was to assess bronchovascular morphology, calculate the ratio of the diameters of bronchial lumen and adjacent artery (BA ratio), and identify those measurements able to discriminate bronchiectasis. We collected quantitative CT (QCT) measures of BA ratios, peak wall attenuation, wall thickness (WT), wall area, and wall area percent (WA%) at matched fourth through sixth airway generations in 21 ever smokers with bronchiectasis (cases) and 21 never-smoking control patients (control airways). In cases, measurements were collected at both bronchiectatic and nonbronchiectatic airways. Logistic analysis and the area under receiver operating characteristic curve (AUC) were used to assess the predictive ability of QCT measurements for bronchiectasis. The whole-lung and fourth through sixth airway generation BA ratio, WT, and WA% were significantly greater in bronchiectasis cases than control patients. The AUCs for the BA ratio to predict bronchiectasis ranged from 0.90 (whole lung) to 0.79 (fourth-generation). AUCs for WT and WA% ranged from 0.72 to 0.75 and from 0.71 to 0.75. The artery diameters but not bronchial diameters were smaller in bronchiectatic than both nonbronchiectatic and control airways (P < .01 for both). Smoking-related increases in the BA ratio appear to be driven by reductions in vascular caliber. QCT measures of BA ratio, WT, and WA% may be useful to objectively identify and quantify bronchiectasis in smokers. ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Estimating apparent maximum muscle stress of trunk extensor muscles in older adults using subject-specific musculoskeletal models.

PubMed

Burkhart, Katelyn A; Bruno, Alexander G; Bouxsein, Mary L; Bean, Jonathan F; Anderson, Dennis E

2018-01-01

Maximum muscle stress (MMS) is a critical parameter in musculoskeletal modeling, defining the maximum force that a muscle of given size can produce. However, a wide range of MMS values have been reported in literature, and few studies have estimated MMS in trunk muscles. Due to widespread use of musculoskeletal models in studies of the spine and trunk, there is a need to determine reasonable magnitude and range of trunk MMS. We measured trunk extension strength in 49 participants over 65 years of age, surveyed participants about low back pain, and acquired quantitative computed tomography (QCT) scans of their lumbar spines. Trunk muscle morphology was assessed from QCT scans and used to create a subject-specific musculoskeletal model for each participant. Model-predicted extension strength was computed using a trunk muscle MMS of 100 N/cm 2 . The MMS of each subject-specific model was then adjusted until the measured strength matched the model-predicted strength (±20 N). We found that measured trunk extension strength was significantly higher in men. With the initial constant MMS value, the musculoskeletal model generally over-predicted trunk extension strength. By adjusting MMS on a subject-specific basis, we found apparent MMS values ranging from 40 to 130 N/cm 2 , with an average of 75.5 N/cm 2 for both men and women. Subjects with low back pain had lower apparent MMS than subjects with no back pain. This work incorporates a unique approach to estimate subject-specific trunk MMS values via musculoskeletal modeling and provides a useful insight into MMS variation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:498-505, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Quantitative data standardization of X-ray based densitometry methods

NASA Astrophysics Data System (ADS)

Sergunova, K. A.; Petraikin, A. V.; Petrjajkin, F. A.; Akhmad, K. S.; Semenov, D. S.; Potrakhov, N. N.

2018-02-01

In the present work is proposed the design of special liquid phantom for assessing the accuracy of quantitative densitometric data. Also are represented the dependencies between the measured bone mineral density values and the given values for different X-ray based densitometry techniques. Shown linear graphs make it possible to introduce correction factors to increase the accuracy of BMD measurement by QCT, DXA and DECT methods, and to use them for standardization and comparison of measurements.

Effect of finite element model loading condition on fracture risk assessment in men and women: the AGES-Reykjavik study.

PubMed

Keyak, J H; Sigurdsson, S; Karlsdottir, G S; Oskarsdottir, D; Sigmarsdottir, A; Kornak, J; Harris, T B; Sigurdsson, G; Jonsson, B Y; Siggeirsdottir, K; Eiriksdottir, G; Gudnason, V; Lang, T F

2013-11-01

Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4-7years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (FPL), posterior (FP) and lateral (FL) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (FStance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p≤0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between FP and fracture in women fell short of statistical significance (p=0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, FPL was 424N (11%) less in subjects with fractures than in controls (p=0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD. © 2013.

A New Material Mapping Procedure for Quantitative Computed Tomography-Based, Continuum Finite Element Analyses of the Vertebra

PubMed Central

Unnikrishnan, Ginu U.; Morgan, Elise F.

2011-01-01

Inaccuracies in the estimation of material properties and errors in the assignment of these properties into finite element models limit the reliability, accuracy, and precision of quantitative computed tomography (QCT)-based finite element analyses of the vertebra. In this work, a new mesh-independent, material mapping procedure was developed to improve the quality of predictions of vertebral mechanical behavior from QCT-based finite element models. In this procedure, an intermediate step, called the material block model, was introduced to determine the distribution of material properties based on bone mineral density, and these properties were then mapped onto the finite element mesh. A sensitivity study was first conducted on a calibration phantom to understand the influence of the size of the material blocks on the computed bone mineral density. It was observed that varying the material block size produced only marginal changes in the predictions of mineral density. Finite element (FE) analyses were then conducted on a square column-shaped region of the vertebra and also on the entire vertebra in order to study the effect of material block size on the FE-derived outcomes. The predicted values of stiffness for the column and the vertebra decreased with decreasing block size. When these results were compared to those of a mesh convergence analysis, it was found that the influence of element size on vertebral stiffness was less than that of the material block size. This mapping procedure allows the material properties in a finite element study to be determined based on the block size required for an accurate representation of the material field, while the size of the finite elements can be selected independently and based on the required numerical accuracy of the finite element solution. The mesh-independent, material mapping procedure developed in this study could be particularly helpful in improving the accuracy of finite element analyses of vertebroplasty and spine metastases, as these analyses typically require mesh refinement at the interfaces between distinct materials. Moreover, the mapping procedure is not specific to the vertebra and could thus be applied to many other anatomic sites. PMID:21823740

Reproducibility of Direct Quantitative Measures of Cortical Bone Micro-architecture of the Distal Radius and Tibia by HR-pQCT

PubMed Central

Burghardt, Andrew J.; Buie, Helen R.; Laib, Andres; Majumdar, Sharmila; Boyd, Steven K.

2010-01-01

Quantitative cortical micro-architectural endpoints are important for understanding structure-function relations in the context of fracture risk and therapeutic efficacy. This technique study details new image-processing methods to automatically segment and directly quantify cortical density, geometry, and micro-architecture from HR-pQCT images of the distal radius and tibia. An automated segmentation technique was developed to identify the periosteal and endosteal margins of the distal radius and tibia, and detect intra-cortical pore space morphologically consistent with Haversian canals. The reproducibility of direct quantitative cortical bone indices based on this method was assessed in a pooled dataset of 56 subjects with two repeat acquisitions for each site. The in vivo precision error was characterized using root mean square coefficient of variation (RMSCV%) from which, the least significant change (LSC) was calculated. Bland-Altman plots were used to characterize bias in the precision estimates. The reproducibility of cortical density and cross-sectional area measures was high (RMSCV <1% and <1.5%, respectively) with good agreement between young and elder medians. The LSC for cortical porosity (Ct.Po) was somewhat smaller in the radius (0.58%) compared with the distal tibia (0.84%) and significantly different between young and elder medians in the distal tibia (LSC: 0.75% vs. 0.92%; p<0.001). The LSC for pore diameter and distribution (Po.Dm and Po.Dm.SD) ranged between 15 and 23μm. Bland-Altman analysis revealed moderate bias for integral measures of area and volume, but not density nor microarchitecture. This study indicates HR-pQCT measures of cortical bone density and architecture can be measured in vivo with high reproducibility and limited bias across a biologically relevant range of values. The results of this study provide informative data for the design of future clinical studies of bone quality. PMID:20561906

Measurement-device-independent quantum coin tossing

NASA Astrophysics Data System (ADS)

Zhao, Liangyuan; Yin, Zhenqiang; Wang, Shuang; Chen, Wei; Chen, Hua; Guo, Guangcan; Han, Zhengfu

2015-12-01

Quantum coin tossing (QCT) is an important primitive of quantum cryptography and has received continuous interest. However, in practical QCT, Bob's detectors can be subjected to detector-side channel attacks launched by dishonest Alice, which will possibly make the protocol completely insecure. Here, we report a simple strategy of a detector-blinding attack based on a recent experiment. To remove all the detector side channels, we present a solution of measurement-device-independent QCT (MDI-QCT). This method is similar to the idea of MDI quantum key distribution (QKD). MDI-QCT is loss tolerant with single-photon sources and has the same bias as the original loss-tolerant QCT under a coherent attack. Moreover, it provides the potential advantage of doubling the secure distance for some special cases. Finally, MDI-QCT can also be modified to fit the weak coherent-state sources. Thus, based on the rapid development of practical MDI-QKD, our proposal can be implemented easily.

Rhorix: An interface between quantum chemical topology and the 3D graphics program blender

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mills, Matthew J. L.; Sale, Kenneth L.; Simmons, Blake A.

Journal of Computational Chemistry Published by Wiley Periodicals, Inc. Chemical research is assisted by the creation of visual representations that map concepts (such as atoms and bonds) to 3D objects. These concepts are rooted in chemical theory that predates routine solution of the Schrödinger equation for systems of interesting size. The method of Quantum Chemical Topology (QCT) provides an alternative, parameter-free means to understand chemical phenomena directly from quantum mechanical principles. Representation of the topological elements of QCT has lagged behind the best tools available. Here, we describe a general abstraction (and corresponding file format) that permits the definition ofmore » mappings between topological objects and their 3D representations. Possible mappings are discussed and a canonical example is suggested, which has been implemented as a Python “Add-On” named Rhorix for the state-of-the-art 3D modeling program Blender. This allows chemists to use modern drawing tools and artists to access QCT data in a familiar context. Finally, a number of examples are discussed..« less

Rhorix: An interface between quantum chemical topology and the 3D graphics program blender

PubMed Central

Sale, Kenneth L.; Simmons, Blake A.; Popelier, Paul L. A.

2017-01-01

Chemical research is assisted by the creation of visual representations that map concepts (such as atoms and bonds) to 3D objects. These concepts are rooted in chemical theory that predates routine solution of the Schrödinger equation for systems of interesting size. The method of Quantum Chemical Topology (QCT) provides an alternative, parameter‐free means to understand chemical phenomena directly from quantum mechanical principles. Representation of the topological elements of QCT has lagged behind the best tools available. Here, we describe a general abstraction (and corresponding file format) that permits the definition of mappings between topological objects and their 3D representations. Possible mappings are discussed and a canonical example is suggested, which has been implemented as a Python “Add‐On” named Rhorix for the state‐of‐the‐art 3D modeling program Blender. This allows chemists to use modern drawing tools and artists to access QCT data in a familiar context. A number of examples are discussed. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:28857244

Rhorix: An interface between quantum chemical topology and the 3D graphics program blender

DOE PAGES

Mills, Matthew J. L.; Sale, Kenneth L.; Simmons, Blake A.; ...

2017-08-31

Journal of Computational Chemistry Published by Wiley Periodicals, Inc. Chemical research is assisted by the creation of visual representations that map concepts (such as atoms and bonds) to 3D objects. These concepts are rooted in chemical theory that predates routine solution of the Schrödinger equation for systems of interesting size. The method of Quantum Chemical Topology (QCT) provides an alternative, parameter-free means to understand chemical phenomena directly from quantum mechanical principles. Representation of the topological elements of QCT has lagged behind the best tools available. Here, we describe a general abstraction (and corresponding file format) that permits the definition ofmore » mappings between topological objects and their 3D representations. Possible mappings are discussed and a canonical example is suggested, which has been implemented as a Python “Add-On” named Rhorix for the state-of-the-art 3D modeling program Blender. This allows chemists to use modern drawing tools and artists to access QCT data in a familiar context. Finally, a number of examples are discussed..« less

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.;

Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study

PubMed Central

Stathopoulos, K.D.; Zoubos, A.B.; Papaioannou, N.A.; Mastrokalos, D.; Galanos, A.; Papagelopoulos, P.J.; Skarantavos, G.

2016-01-01

Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20-79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI). Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID:27282455

Differences in Trabecular Microstructure Between Black and White Women Assessed by Individual Trabecular Segmentation Analysis of HR-pQCT Images

PubMed Central

Putman, Melissa S; Yu, Elaine W; Lin, David; Darakananda, Karin; Finkelstein, Joel S; Bouxsein, Mary L

2017-01-01

Black women have lower fracture risk compared with white women, which may be partly explained by improved volumetric bone mineral density (vBMD) and bone microarchitecture primarily within the cortical bone compartment. To determine if there are differences in trabecular microstructure, connectivity, and alignment according to race/ethnicity, we performed individual trabecular segmentation (ITS) analyses on high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia in 273 peri- and postmenopausal black (n = 100) and white (n = 173) women participating in the Study of Women’s Health Across the Nation in Boston. Unadjusted analyses showed that black women had greater trabecular plate volume fraction, plate thickness, plate number density, and plate surface area along with greater axial alignment of trabeculae, whereas white women had greater trabecular rod tissue fraction (p < 0.05 for all). Adjustment for clinical covariates augmented these race/ethnicity-related differences in plates and rods, such that white women had greater trabecular rod number density and rod-rod connectivity, whereas black women continued to have superior plate structural characteristics and axial alignment (p < 0.05 for all). These differences remained significant after adjustment for hip BMD and trabecular vBMD. In conclusion, black women had more plate-like trabecular morphology and higher axial alignment of trabeculae, whereas white women had more rod-like trabeculae. These differences may contribute to the improved bone strength and lower fracture risk observed in black women. PMID:27958659

Site-Specific Variations in Bone Mineral Density under Systemic Conditions Inducing Osteoporosis in Minipigs.

PubMed

Schulz, Matthias C; Kowald, Jan; Estenfelder, Sven; Jung, Roland; Kuhlisch, Eberhard; Eckelt, Uwe; Mai, Ronald; Hofbauer, Lorenz C; Stroszczynski, Christian; Stadlinger, Bernd

2017-01-01

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible ( p < 0.001) and the maxilla ( p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.

Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.

PubMed

Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng

2016-09-01

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiation exposure in X-ray-based imaging techniques used in osteoporosis

PubMed Central

Adams, Judith E.; Guglielmi, Giuseppe; Link, Thomas M.

2010-01-01

Recent advances in medical X-ray imaging have enabled the development of new techniques capable of assessing not only bone quantity but also structure. This article provides (a) a brief review of the current X-ray methods used for quantitative assessment of the skeleton, (b) data on the levels of radiation exposure associated with these methods and (c) information about radiation safety issues. Radiation doses associated with dual-energy X-ray absorptiometry are very low. However, as with any X-ray imaging technique, each particular examination must always be clinically justified. When an examination is justified, the emphasis must be on dose optimisation of imaging protocols. Dose optimisation is more important for paediatric examinations because children are more vulnerable to radiation than adults. Methods based on multi-detector CT (MDCT) are associated with higher radiation doses. New 3D volumetric hip and spine quantitative computed tomography (QCT) techniques and high-resolution MDCT for evaluation of bone structure deliver doses to patients from 1 to 3 mSv. Low-dose protocols are needed to reduce radiation exposure from these methods and minimise associated health risks. PMID:20559834

Segmentation of cortical bone using fast level sets

NASA Astrophysics Data System (ADS)

Chowdhury, Manish; Jörgens, Daniel; Wang, Chunliang; Smedby, Årjan; Moreno, Rodrigo

2017-02-01

Cortical bone plays a big role in the mechanical competence of bone. The analysis of cortical bone requires accurate segmentation methods. Level set methods are usually in the state-of-the-art for segmenting medical images. However, traditional implementations of this method are computationally expensive. This drawback was recently tackled through the so-called coherent propagation extension of the classical algorithm which has decreased computation times dramatically. In this study, we assess the potential of this technique for segmenting cortical bone in interactive time in 3D images acquired through High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The obtained segmentations are used to estimate cortical thickness and cortical porosity of the investigated images. Cortical thickness and Cortical porosity is computed using sphere fitting and mathematical morphological operations respectively. Qualitative comparison between the segmentations of our proposed algorithm and a previously published approach on six images volumes reveals superior smoothness properties of the level set approach. While the proposed method yields similar results to previous approaches in regions where the boundary between trabecular and cortical bone is well defined, it yields more stable segmentations in challenging regions. This results in more stable estimation of parameters of cortical bone. The proposed technique takes few seconds to compute, which makes it suitable for clinical settings.

Thermal Rate Coefficients for the Astrochemical Process C + CH+ → C2+ + H by Ring Polymer Molecular Dynamics.

PubMed

Rampino, Sergio; Suleimanov, Yury V

2016-12-22

Thermal rate coefficients for the astrochemical reaction C + CH + → C 2 + + H were computed in the temperature range 20-300 K by using novel rate theory based on ring polymer molecular dynamics (RPMD) on a recently published bond-order based potential energy surface and compared with previous Langevin capture model (LCM) and quasi-classical trajectory (QCT) calculations. Results show that there is a significant discrepancy between the RPMD rate coefficients and the previous theoretical results that can lead to overestimation of the rate coefficients for the title reaction by several orders of magnitude at very low temperatures. We argue that this can be attributed to a very challenging energy profile along the reaction coordinate for the title reaction, not taken into account in extenso by either the LCM or QCT approximation. In the absence of any rigorous quantum mechanical or experimental results, the computed RPMD rate coefficients represent state-of-the-art estimates to be included in astrochemical databases and kinetic networks.

Communication: rate coefficients from quasiclassical trajectory calculations from the reverse reaction: The Mu + H2 reaction re-visited.

PubMed

Homayoon, Zahra; Jambrina, Pablo G; Aoiz, F Javier; Bowman, Joel M

2012-07-14

In a previous paper [P. G. Jambrina et al., J. Chem. Phys. 135, 034310 (2011)] various calculations of the rate coefficient for the Mu + H(2) → MuH + H reaction were presented and compared to experiment. The widely used standard quasiclassical trajectory (QCT) method was shown to overestimate the rate coefficients by several orders of magnitude over the temperature range 200-1000 K. This was attributed to a major failure of that method to describe the correct threshold for the reaction owing to the large difference in zero-point energies (ZPE) of the reactant H(2) and product MuH (∼0.32 eV). In this Communication we show that by performing standard QCT calculations for the reverse reaction and then applying detailed balance, the resulting rate coefficient is in very good agreement with the other computational results that respect the ZPE, (as well as with the experiment) but which are more demanding computationally.

Communication: Rate coefficients from quasiclassical trajectory calculations from the reverse reaction: The Mu + H2 reaction re-visited

NASA Astrophysics Data System (ADS)

Homayoon, Zahra; Jambrina, Pablo G.; Aoiz, F. Javier; Bowman, Joel M.

2012-07-01

In a previous paper [P. G. Jambrina et al., J. Chem. Phys. 135, 034310 (2011), 10.1063/1.3611400] various calculations of the rate coefficient for the Mu + H2 → MuH + H reaction were presented and compared to experiment. The widely used standard quasiclassical trajectory (QCT) method was shown to overestimate the rate coefficients by several orders of magnitude over the temperature range 200-1000 K. This was attributed to a major failure of that method to describe the correct threshold for the reaction owing to the large difference in zero-point energies (ZPE) of the reactant H2 and product MuH (˜0.32 eV). In this Communication we show that by performing standard QCT calculations for the reverse reaction and then applying detailed balance, the resulting rate coefficient is in very good agreement with the other computational results that respect the ZPE, (as well as with the experiment) but which are more demanding computationally.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

PubMed

Chapurlat, R D; Laroche, M; Thomas, T; Rouanet, S; Delmas, P D; de Vernejoul, M-C

2013-01-01

We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

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

NASA Technical Reports Server (NTRS)

Vasadi, Lukas J.; Spector, Elizabeth R.; Smith, Scott A.; Yardley, Gregory L.; Evans, Harlan J.; Sibonga, Jean D.

2016-01-01

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.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

PubMed

Hung, V W Y; Zhu, T Y; Cheung, W-H; Fong, T-N; Yu, F W P; Hung, L-K; Leung, K-S; Cheng, J C Y; Lam, T-P; Qin, L

2015-06-01

In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Alterations of bone density, microstructure, and strength of the distal radius in male patients with rheumatoid arthritis: a case-control study with HR-pQCT.

PubMed

Zhu, Tracy Y; Griffith, James F; Qin, Ling; Hung, Vivian W; Fong, Tsz-Ning; Au, Sze-Ki; Li, Martin; Lam, Yvonne Yi-On; Wong, Chun-Kwok; Kwok, Anthony W; Leung, Ping-Chung; Li, Edmund K; Tam, Lai-Shan

2014-09-01

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation. © 2014 American Society for Bone and Mineral Research.

Mechanical torque measurement predicts load to implant cut-out: a biomechanical study investigating DHS anchorage in femoral heads.

PubMed

Suhm, Norbert; Hengg, Clemens; Schwyn, Ronald; Windolf, Markus; Quarz, Volker; Hänni, Markus

2007-08-01

Bone strength plays an important role in implant anchorage. Bone mineral density (BMD) is used as surrogate parameter to quantify bone strength and to predict implant anchorage. BMD can be measured by means of quantitative computer tomography (QCT) or dual energy X-ray absorptiometry (DXA). These noninvasive methods for BMD measurement are not available pre- or intra-operatively. Instead, the surgeon could determine bone strength by direct mechanical measurement. We have evaluated mechanical torque measurement for (A) its capability to quantify local bone strength and (B) its predictive value towards load at implant cut-out. Our experimental study was performed using sixteen paired human cadaver proximal femurs. BMD was determined for all specimens by QCT. The torque to breakaway of the cancellous bone structure (peak torque) was measured by means of a mechanical probe at the exact position of subsequent DHS placement. The fixation strength of the DHS achieved was assessed by cyclic loading in a stepwise protocol beginning with 1,500 N increasing 500 N every 5,000 cycles until 4,000 N. A highly significant correlation of peak torque with BMD (QCT) was found (r = 0.902, r (2) = 0.814, P < 0.001). Peak torque correlated highly significant with the load at implant cut-out (r = 0.795, P < 0.001). All specimens with a measured peak torque below 6.79 Nm failed at the first load level of 1,500 N. The specimens with a peak torque above 8.63 Nm survived until the last load level of 4,000 N. Mechanical peak torque measurement is able to quantify bone strength. In an experimental setup, peak torque identifies those specimens that are likely to fail at low load. In clinical routine, implant migration and cut-out depend on several parameters, which are difficult to control, such as fracture type, fracture reduction achieved, and implant position. The predictive value of peak torque towards cut-out in a clinical set-up therefore has to be carefully validated.

QCT/FEA predictions of femoral stiffness are strongly affected by boundary condition modeling

PubMed Central

Rossman, Timothy; Kushvaha, Vinod; Dragomir-Daescu, Dan

2015-01-01

Quantitative computed tomography-based finite element models of proximal femora must be validated with cadaveric experiments before using them to assess fracture risk in osteoporotic patients. During validation it is essential to carefully assess whether the boundary condition modeling matches the experimental conditions. This study evaluated proximal femur stiffness results predicted by six different boundary condition methods on a sample of 30 cadaveric femora and compared the predictions with experimental data. The average stiffness varied by 280% among the six boundary conditions. Compared with experimental data the predictions ranged from overestimating the average stiffness by 65% to underestimating it by 41%. In addition we found that the boundary condition that distributed the load to the contact surfaces similar to the expected contact mechanics predictions had the best agreement with experimental stiffness. We concluded that boundary conditions modeling introduced large variations in proximal femora stiffness predictions. PMID:25804260

A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation.

PubMed

Barr, R Graham; Berkowitz, Eugene A; Bigazzi, Francesca; Bode, Frederick; Bon, Jessica; Bowler, Russell P; Chiles, Caroline; Crapo, James D; Criner, Gerard J; Curtis, Jeffrey L; Dass, Chandra; Dirksen, Asger; Dransfield, Mark T; Edula, Goutham; Erikkson, Leif; Friedlander, Adam; Galperin-Aizenberg, Maya; Gefter, Warren B; Gierada, David S; Grenier, Philippe A; Goldin, Jonathan; Han, MeiLan K; Hanania, Nicola A; Hansel, Nadia N; Jacobson, Francine L; Kauczor, Hans-Ulrich; Kinnula, Vuokko L; Lipson, David A; Lynch, David A; MacNee, William; Make, Barry J; Mamary, A James; Mann, Howard; Marchetti, Nathaniel; Mascalchi, Mario; McLennan, Geoffrey; Murphy, James R; Naidich, David; Nath, Hrudaya; Newell, John D; Pistolesi, Massimo; Regan, Elizabeth A; Reilly, John J; Sandhaus, Robert; Schroeder, Joyce D; Sciurba, Frank; Shaker, Saher; Sharafkhaneh, Amir; Silverman, Edwin K; Steiner, Robert M; Strange, Charlton; Sverzellati, Nicola; Tashjian, Joseph H; van Beek, Edwin J R; Washington, Lacey; Washko, George R; Westney, Gloria; Wood, Susan A; Woodruff, Prescott G

2012-04-01

The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Fast estimation of Colles' fracture load of the distal section of the radius by homogenized finite element analysis based on HR-pQCT.

PubMed

Hosseini, Hadi S; Dünki, Andreas; Fabech, Jonas; Stauber, Martin; Vilayphiou, Nicolas; Pahr, Dieter; Pretterklieber, Michael; Wandel, Jasmin; Rietbergen, Bert van; Zysset, Philippe K

2017-04-01

Fractures of the distal section of the radius (Colles' fractures) occur earlier in life than other osteoporotic fractures. Therefore, they can be interpreted as a warning signal for later, more deleterious fractures of vertebral bodies or the femoral neck. In the past decade, the advent of HR-pQCT allowed a detailed architectural analysis of the distal radius and an automated but time-consuming estimation of its strength with linear micro-finite element (μFE) analysis. Recently, a second generation of HR-pQCT scanner (XtremeCT II, SCANCO Medical, Switzerland) with a resolution beyond 61 μm became available for even more refined biomechanical investigations in vivo. This raises the question how biomechanical outcome variables compare between the original (LR) and the new (HR) scanner resolution. Accordingly, the aim of this work was to validate experimentally a patient-specific homogenized finite element (hFE) analysis of the distal section of the human radius for the fast prediction of Colles' fracture load based on the last generation HR-pQCT. Fourteen pairs of fresh frozen forearms (mean age = 77.5±9) were scanned intact using the high (61 μm) and the low (82 μm) resolution protocols that correspond to the new and original HR-pQCT systems. From each forearm, the 20mm most distal section of the radius were dissected out, scanned with μCT at 16.4 μm and tested experimentally under compression up to failure for assessment of stiffness and ultimate load. Linear and nonlinear hFE models together with linear micro finite element (μFE) models were then generated based on the μCT and HR-pQCT reconstructions to predict the aforementioned mechanical properties of 24 sections. Precision errors of the short term reproducibility of the FE analyses were measured based on the repeated scans of 12 sections. The calculated failure loads correlated strongly with those measured in the experiments: accounting for donor as a random factor, the nonlinear hFE provided a marginal coefficient of determination (R m 2 ) of 0.957 for the high resolution (HR) and 0.948 for the low resolution (LR) protocols, the linear hFE with R m 2 of 0.957 for the HR and 0.947 for the LR protocols. Linear μFE predictions of the ultimate load were similar with an R m 2 of 0.950 for the HR and 0.954 for the LR protocols, respectively. Nonlinear hFE strength computation led to precision errors of 2.2 and 2.3% which were higher than the ones calculated based on the linear hFE (1.6 and 1.9%) and linear μFE (1.2 and 1.6%) for the HR and LR protocols respectively. Computation of the fracture load with nonlinear hFE demanded in average 6h of CPU time which was 3 times faster than with linear μFE, while computation with linear hFE took only a few minutes. This study delivers an extensive experimental and numerical validation for the application of an accurate and fast hFE diagnostic tool to help in identifying individuals who may be at risk of an osteoporotic wrist fracture and to follow up pharmacological and other treatments in such patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone mineral density changes of lumbar spine and femur in osteoporotic patient treated with bisphosphonates and beta-hydroxy-beta-methylbutyrate (HMB): Case report.

PubMed

Tatara, Marcin R; Krupski, Witold; Majer-Dziedzic, Barbara

2017-10-01

Currently available approaches to osteoporosis treatment include application of antiresorptive and anabolic agents influencing bone tissue metabolism. The aim of the study was to present bone mineral density (BMD) changes of lumbar spine in osteoporotic patient treated with bisphosphonates such as ibandronic acid and pamidronic acid, and beta-hydroxy-beta-methylbutyrate (HMB). BMD and volumetric BMD (vBMD) of lumbar spine were measured during the 6 year observation period with the use of dual-energy X-ray absorptiometry (DEXA) and quantitative computed tomography (QCT). The described case report of osteoporotic patient with family history of severe osteoporosis has shown site-dependent response of bone tissue to antiosteoporotic treatment with bisphosphonates. Twenty-five-month treatment with ibandronic acid improved proximal femur BMD with relatively poor effects on lumbar spine BMD. Over 15-month therapy with pamidronic acid was effective to improve lumbar spine BMD, while in the proximal femur the treatment was not effective. A total of 61-week long oral administration with calcium salt of HMB improved vBMD of lumbar spine in the trabecular and cortical bone compartments when monitored by QCT. Positive effects of nearly 2.5 year HMB treatment on BMD of lumbar spine and femur in the patient were also confirmed using DEXA method. The results obtained indicate that HMB may be applied for the effective treatment of osteoporosis in humans. Further studies on wider human population are recommended to evaluate mechanisms influencing bone tissue metabolism by HMB.

Microarchitectural Deterioration of Cortical and Trabecular Bone: Differing Effects of Denosumab and Alendronate

PubMed Central

Seeman, Ego; Delmas, Pierre D; Hanley, David A; Sellmeyer, Deborah; Cheung, Angela M; Shane, Elizabeth; Kearns, Ann; Thomas, Thierry; Boyd, Steven K; Boutroy, Stephanie; Bogado, Cesar; Majumdar, Sharmila; Fan, Michelle; Libanati, Cesar; Zanchetta, Jose

2015-01-01

The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60mg subcutaneous 6 monthly), alendronate (70mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to < .001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. PMID:20222106

Substantial vertebral body osteophytes protect against severe vertebral fractures in compression

PubMed Central

Aubin, Carl-Éric; Chaumoître, Kathia; Mac-Thiong, Jean-Marc; Ménard, Anne-Laure; Petit, Yvan; Garo, Anaïs; Arnoux, Pierre-Jean

2017-01-01

Recent findings suggest that vertebral osteophytes increase the resistance of the spine to compression. However, the role of vertebral osteophytes on the biomechanical response of the spine under fast dynamic compression, up to failure, is unclear. Seventeen human spine specimens composed of three vertebrae (from T5-T7 to T11-L1) and their surrounding soft tissues were harvested from nine cadavers, aged 77 to 92 years. Specimens were imaged using quantitative computer tomography (QCT) for medical observation, classification of the intervertebral disc degeneration (Thomson grade) and measurement of the vertebral trabecular density (VTD), height and cross-sectional area. Specimens were divided into two groups (with (n = 9) or without (n = 8) substantial vertebral body osteophytes) and compressed axially at a dynamic displacement rate of 1 m/s, up to failure. Normalized force-displacement curves, videos and QCT images allowed characterizing failure parameters (force, displacement and energy at failure) and fracture patterns. Results were analyzed using chi-squared tests for sampling distributions and linear regression for correlations between VTD and failure parameters. Specimens with substantial vertebral body osteophytes present higher stiffness (2.7 times on average) and force at failure (1.8 times on average) than other segments. The presence of osteophytes significantly influences the location, pattern and type of fracture. VTD was a good predictor of the dynamic force and energy at failure for specimens without substantial osteophytes. This study also showed that vertebral body osteophytes provide a protective mechanism to the underlying vertebra against severe compression fractures. PMID:29065144

LRP5 gene polymorphism and cortical bone.

PubMed

Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

2010-08-01

There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21-94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women.

Experimental Traumatic Brain Injury Induces Bone Loss in Rats.

PubMed

Brady, Rhys D; Shultz, Sandy R; Sun, Mujun; Romano, Tania; van der Poel, Chris; Wright, David K; Wark, John D; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

2016-12-01

Few studies have investigated the influence of traumatic brain injury (TBI) on bone homeostasis; however, pathophysiological mechanisms involved in TBI have potential to be detrimental to bone. The current study assessed the effect of experimental TBI in rats on the quantity and quality of two different weight-bearing bones, the femur and humerus. Rats were randomly assigned into either sham or lateral fluid percussion injury (FPI) groups. Open-field testing to assess locomotion was conducted at 1, 4, and 12 weeks post-injury, with the rats killed at 1 and 12 weeks post-injury. Bones were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometric analysis, and three-point bending. pQCT analysis revealed that at 1 and 12 weeks post-injury, the distal metaphyseal region of femora from FPI rats had reduced cortical content (10% decrease at 1 week, 8% decrease at 12 weeks; p < 0.01) and cortical thickness (10% decrease at 1 week, 11% decrease at 12 weeks p < 0.001). There was also a 23% reduction in trabecular bone volume ratio at 1 week post-injury and a 27% reduction at 12 weeks post-injury in FPI rats compared to sham (p < 0.001). There were no differences in bone quantity and mechanical properties of the femoral midshaft between sham and TBI animals. There were no differences in locomotor outcomes, which suggested that post-TBI changes in bone were not attributed to immobility. Taken together, these findings indicate that this rat model of TBI was detrimental to bone and suggests a link between TBI and altered bone remodeling.

Alterations of bone microstructure and strength in end-stage renal failure.

PubMed

Trombetti, A; Stoermann, C; Chevalley, T; Van Rietbergen, B; Herrmann, F R; Martin, P-Y; Rizzoli, R

2013-05-01

End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6 years) and 33 age-matched healthy controls. Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes" working group PTH level categories (r = 0.36, p < 0.04). BMI correlated positively with trabecular number (r = 0.4, p < 0.02) and negatively with trabecular spacing (r = -0.37, p < 0.03) and trabecular network heterogeneity (r = -0.4, p < 0.02). Biomechanics positively correlated with BMI and negatively with BALP. Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patients.

Capture and dissociation in the complex-forming CH + H2 → CH2 + H, CH + H2 reactions.

PubMed

González, Miguel; Saracibar, Amaia; Garcia, Ernesto

2011-02-28

The rate coefficients for the capture process CH + H(2)→ CH(3) and the reactions CH + H(2)→ CH(2) + H (abstraction), CH + H(2) (exchange) have been calculated in the 200-800 K temperature range, using the quasiclassical trajectory (QCT) method and the most recent global potential energy surface. The reactions, which are of interest in combustion and in astrochemistry, proceed via the formation of long-lived CH(3) collision complexes, and the three H atoms become equivalent. QCT rate coefficients for capture are in quite good agreement with experiments. However, an important zero point energy (ZPE) leakage problem occurs in the QCT calculations for the abstraction, exchange and inelastic exit channels. To account for this issue, a pragmatic but accurate approach has been applied, leading to a good agreement with experimental abstraction rate coefficients. Exchange rate coefficients have also been calculated using this approach. Finally, calculations employing QCT capture/phase space theory (PST) models have been carried out, leading to similar values for the abstraction rate coefficients as the QCT and previous quantum mechanical capture/PST methods. This suggests that QCT capture/PST models are a good alternative to the QCT method for this and similar systems.

Skeletal adaptations associated with pre-pubertal gymnastics participation as determined by DXA and pQCT: a systematic review and meta-analysis.

PubMed

Burt, Lauren A; Greene, David A; Ducher, Gaele; Naughton, Geraldine A

2013-05-01

Participation in gymnastics prior to puberty offers an intriguing and unique model, particularly in girls. The individuality comes from both upper and lower limbs being exposed to high mechanical loading through year long intensive training programs, initiated at a young age. Studying this unique model and the associated changes in musculoskeletal health during growth is an area of specific interest. Previous reviews on gymnastics participation and bone health have been broad; and not limited to a particular maturation period, such as pre-puberty. To determine the difference in skeletal health between pre-pubertal girls participating in gymnastics compared with non-gymnasts. Meta-analysis. Following a systematic search, 17 studies were included in this meta-analysis. All studies used dual-energy X-ray absorptiometry to assess bone mineral density and bone mineral content. In addition, two studies included peripheral quantitative computed tomography. Following the implementation of a random effects model, gymnasts were found to have greater bone properties than non-gymnasts. The largest difference in bone health between gymnasts and non-gymnasts was observed in peripheral quantitative computed tomography-derived volumetric bone mineral density at the distal radius (d=1.06). Participation in gymnastics during pre-pubertal growth was associated with skeletal health benefits, particularly to the upper body. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Quercetin, a Flavonoid Antioxidant, Ameliorated Procarbazine-Induced Oxidative Damage to Murine Tissues

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Adeyemo, Oluwatobi Adewumi; Ola, Olaniyi Solomon; Olotu, Olaoluwa Oluwaseun; Echebiri, Roseline Chinonye

2015-01-01

Procarbazine (PCZ) (indicated in Hodgkin’s disease), is an alkylating agent known to generate free radicals in vivo, while Quercetin (QCT) is a flavonoid antioxidant with proven free radical scavenging capacity. This study investigated the protective effects of QCT on PCZ-induced oxidative damage in the rat. Male Wistar rats (160–180 g) were randomized into five groups (n = 5/group): I (control), II PCZ-treated (2 mg/kg body weight (bw) for seven days); III pre-treated with QCT (20 mg/kg bw) for seven days, followed by PCZ for seven days; IV co-treated with PCZ and QCT for seven days and V administered QCT alone for seven days. PCZ caused a significant increase in plasma total bilirubin, urea, and creatinine when compared with control (P < 0.05). Similarly, plasma activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GT) were significantly increased in the PCZ-treated group relative to control. Furthermore, PCZ caused a significant decrease in the activities of hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) as well as levels of ascorbic acid (AA) and glutathione (GSH). This was followed by a significant increase in hepatic malondialdehyde (MDA) content. However, QCT pre-treatment and co-treatment ameliorated the PCZ-induced changes in plasma levels of urea, creatinine, and bilirubin as well as the activities of ALP, AST, ALT, and GGT. QCT also ameliorated hepatic AA and GSH levels and the activities of SOD, CAT, and GST. This all suggests that QCT protected against PCZ-induced oxidative damage in rats. PMID:26783707

Tyrosinase overexpression promotes ATM-dependent p53 phosphorylation by quercetin and sensitizes melanoma cells to dacarbazine.

PubMed

Thangasamy, Thilakavathy; Sittadjody, Sivanandane; Limesand, Kirsten H; Burd, Randy

2008-01-01

Dacarbazine (DTIC) has been used for the treatment of melanoma for decades. However, monotherapy with this chemotherapeutic agent results only in moderate response rates. To improve tumor response to DTIC current clinical trials in melanoma focus on combining a novel targeted agent with chemotherapy. Here, we demonstrate that tyrosinase which is commonly overexpressed in melanoma activates the bioflavonoid quercetin (Qct) and promotes an ataxia telangiectasia mutated (ATM)-dependent DNA damage response. This response sensitizes melanoma cells that overexpress tyrosinase to DTIC. In DB-1 melanoma cells that overexpress tyrosinase (Tyr(+) cells), the threshold for phosphorylation of ATM and p53 at serine 15 was observed at a low dose of Qct (25 microM) when compared to the mock transfected pcDNA3 cells, which required a higher dose (75 microM). Both pcDNA3 and Tyr(+) DB-1 cells demonstrated similar increases in phosphorylation of p53 at other serine sites, but in the Tyr(+) cells, DNApk expression was found to be reduced compared to control cells, indicating a shift towards an ATM-mediated response. The DB-1 control cells were resistant to DTIC, but were sensitized to apoptosis with high dose Qct, while Tyr(+) cells were sensitized to DTIC with low or high dose Qct. Qct also sensitized SK Mel 5 (p53 wildtype) and 28 (p53 mutant) cells to DTIC. However, when SK Mel 5 cells were transiently transfected with tyrosinase and treated with Qct plus DTIC, SK Mel 5 cells demonstrated a more than additive induction of apoptosis. Therefore, this study demonstrates that tyrosinase overexpression promotes an ATM-dependent p53 phosphorylation by Qct treatment and sensitizes melanoma cells to dacarbazine. In conclusion, these results suggest that Qct or Qct analogues may significantly improve DTIC response rates in tumors that express tyrosinase.

Tyrosinase Overexpression Promotes ATM-Dependent p53 Phosphorylation by Quercetin and Sensitizes Melanoma Cells to Dacarbazine

PubMed Central

Thangasamy, Thilakavathy; Sittadjody, Sivanandane; H. Limesand, Kirsten; Burd, Randy

2008-01-01

Dacarbazine (DTIC) has been used for the treatment of melanoma for decades. However, monotherapy with this chemotherapeutic agent results only in moderate response rates. To improve tumor response to DTIC current clinical trials in melanoma focus on combining a novel targeted agent with chemotherapy. Here, we demonstrate that tyrosinase which is commonly overexpressed in melanoma activates the bioflavonoid quercetin (Qct) and promotes an ataxia telangiectasia mutated (ATM)-dependent DNA damage response. This response sensitizes melanoma cells that overexpress tyrosinase to DTIC. In DB-1 melanoma cells that overexpress tyrosinase (Tyr cells), the threshold for phosphorylation of ATM and p53 at serine 15 was observed at a low dose of Qct (25 μM) when compared to the mock transfected pcDNA3 cells, which required a higher dose (75 μM). Both pcDNA3 and Tyr DB-1 cells demonstrated similar increases in phosphorylation of p53 at other serine sites, but in the Tyr cells, DNApk expression was found to be reduced compared to control cells, indicating a shift towards an ATM-mediated response. The DB-1 control cells were resistant to DTIC, but were sensitized to apoptosis with high dose Qct, while Tyr cells were sensitized to DTIC with low or high dose Qct. Qct also sensitized SK Mel 5 (p53 wildtype) and 28 (p53 mutant) cells to DTIC. However, when SK Mel 5 cells were transiently transfected with tyrosinase and treated with Qct plus DTIC, SK Mel 5 cells demonstrated a more than additive induction of apoptosis. Therefore, this study demonstrates that tyrosinase overexpression promotes an ATM-dependent p53 phosphorylation by Qct treatment and sensitizes melanoma cells to dacarbazine. In conclusion, these results suggest that Qct or Qct analogues may significantly improve DTIC response rates in tumors that express tyrosinase. PMID:18791269

Evaluation of AISI Type 304 stainless steel as a suitable surface material for evaluating the efficacy of peracetic acid-based disinfectants against Clostridium difficile spores.

PubMed

Black, Elaine; Owens, Krista; Staub, Richard; Li, Junzhong; Mills, Kristen; Valenstein, Justin; Hilgren, John

2017-01-01

Disinfectants play an important role in controlling microbial contamination on hard surfaces in hospitals. The effectiveness of disinfectants in real life can be predicted by laboratory tests that measure killing of microbes on carriers. The modified Quantitative Disk Carrier Test (QCT-2) is a standard laboratory method that employs American Iron and Steel Institute (AISI) Type 430 stainless steel carriers to measure hospital disinfectant efficacy against Clostridium difficile spores. The formation of a rust-colored precipitate was observed on Type 430 carriers when testing a peracetic acid (PAA)-based disinfectant with the QCT-2 method. It was hypothesized that the precipitate was indicative of corrosion of the Type 430 carrier, and that corrosion could impact efficacy results. The objective of this study was to compare the suitability of AISI Type 430 to Type 304 stainless steel carriers for evaluating PAA-based disinfectants using the QCT-2 method. Type 304 is more corrosion-resistant than Type 430, is ubiquitous in healthcare environments, and is used in other standard methods. Suitability of the carriers was evaluated by comparing their impacts on efficacy results and PAA degradation rates. In efficacy tests with 1376 ppm PAA, reductions of C. difficile spores after 5, 7 and 10 minutes on Type 430 carriers were at least about 1.5 log10 lower than reductions on Type 304 carriers. In conditions simulating a QCT-2 test, PAA concentration with Type 430 carriers was reduced by approximately 80% in 10 minutes, whereas PAA concentration in the presence of Type 304 carriers remained stable. Elemental analyses of residues on each carrier type after efficacy testing were indicative of corrosion on the Type 430 carrier. Use of Type 430 stainless steel carriers for measuring the efficacy of PAA-based disinfectants should be avoided as it can lead to an underestimation of real life sporicidal efficacy. Type 304 stainless steel carriers are recommended as a suitable alternative.

Evaluation of AISI Type 304 stainless steel as a suitable surface material for evaluating the efficacy of peracetic acid-based disinfectants against Clostridium difficile spores

PubMed Central

Owens, Krista; Staub, Richard; Li, Junzhong; Mills, Kristen; Valenstein, Justin; Hilgren, John

2017-01-01

Disinfectants play an important role in controlling microbial contamination on hard surfaces in hospitals. The effectiveness of disinfectants in real life can be predicted by laboratory tests that measure killing of microbes on carriers. The modified Quantitative Disk Carrier Test (QCT-2) is a standard laboratory method that employs American Iron and Steel Institute (AISI) Type 430 stainless steel carriers to measure hospital disinfectant efficacy against Clostridium difficile spores. The formation of a rust-colored precipitate was observed on Type 430 carriers when testing a peracetic acid (PAA)-based disinfectant with the QCT-2 method. It was hypothesized that the precipitate was indicative of corrosion of the Type 430 carrier, and that corrosion could impact efficacy results. The objective of this study was to compare the suitability of AISI Type 430 to Type 304 stainless steel carriers for evaluating PAA-based disinfectants using the QCT-2 method. Type 304 is more corrosion-resistant than Type 430, is ubiquitous in healthcare environments, and is used in other standard methods. Suitability of the carriers was evaluated by comparing their impacts on efficacy results and PAA degradation rates. In efficacy tests with 1376 ppm PAA, reductions of C. difficile spores after 5, 7 and 10 minutes on Type 430 carriers were at least about 1.5 log10 lower than reductions on Type 304 carriers. In conditions simulating a QCT-2 test, PAA concentration with Type 430 carriers was reduced by approximately 80% in 10 minutes, whereas PAA concentration in the presence of Type 304 carriers remained stable. Elemental analyses of residues on each carrier type after efficacy testing were indicative of corrosion on the Type 430 carrier. Use of Type 430 stainless steel carriers for measuring the efficacy of PAA-based disinfectants should be avoided as it can lead to an underestimation of real life sporicidal efficacy. Type 304 stainless steel carriers are recommended as a suitable alternative. PMID:29065168

Simultaneous determination of mequindox, quinocetone, and their major metabolites in chicken and pork by UPLC-MS/MS.

PubMed

Li, Yanshen; Liu, Kaili; Beier, Ross C; Cao, Xingyuan; Shen, Jianzhong; Zhang, Suxia

2014-10-01

This report presents a UPLC-MS/MS method for determination of mequindox (MEQ), quinocetone (QCT) and their 11 metabolites in chicken and pork samples. Following extraction process with acetonitrile-ethyl acetate, acidulation, and re-extraction with ethyl acetate in turn, target analytes were further purified using C18 solid phase extraction (SPE) cartridges for UPLC-MS/MS analysis. Validation was processed with mean recoveries from 69.1% to 113.3% with intra-day relative standard deviation (RSD) <14.7%, inter-day RSD <19.2%, and limit of detection between 0.05 and 1.0 μg/kg for each analytes. The verified method was successfully applied to the quantitative determination of commercial samples. This developed procedure will help to control food animal products with MEQ and QCT residues, and facilitate further pharmacokinetic and residue studies of similar quinoxaline-1,4-dioxide veterinary drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Geometry reconstruction method for patient-specific finite element models for the assessment of tibia fracture risk in osteogenesis imperfecta.

PubMed

Caouette, Christiane; Ikin, Nicole; Villemure, Isabelle; Arnoux, Pierre-Jean; Rauch, Frank; Aubin, Carl-Éric

2017-04-01

Lower limb deformation in children with osteogenesis imperfecta (OI) impairs ambulation and may lead to fracture. Corrective surgery is based on empirical assessment criteria. The objective was to develop a reconstruction method of the tibia for OI patients that could be used as input of a comprehensive finite element model to assess fracture risks. Data were obtained from three children with OI and tibia deformities. Four pQCT scans were registered to biplanar radiographs, and a template mesh was deformed to fit the bone outline. Cortical bone thickness was computed. Sensitivity of the model to missing slices of pQCT was assessed by calculating maximal von Mises stress for a vertical hopping load case. Sensitivity of the model to ±5 % of cortical thickness measurements was assessed by calculating loads at fracture. Difference between the mesh contour and bone outline on the radiographs was below 1 mm. Removal of one pQCT slice increased maximal von Mises stress by up to 10 %. Simulated ±5 % variation of cortical bone thickness leads to variations of up to 4.1 % on predicted fracture loads. Using clinically available tibia imaging from children with OI, the developed reconstruction method allowed the building of patient-specific finite element models.

Peri-implant bone density in senile osteoporosis-changes from implant placement to osseointegration.

PubMed

Beppu, Kensuke; Kido, Hirofumi; Watazu, Akira; Teraoka, Kay; Matsuura, Masaro

2013-04-01

The aim of this study was to examine healing over time after implant body placement in a senile osteoporosis model and a control group. In this study, 16-week-old male mice were used. The senile osteoporosis model consisted of senescence-accelerated prone 6 mice and the control group consisted of senescence-accelerated resistant 1 mice. Titanium-coated plastic implants were used as experimental implants whose dimensions were 3.0 mm in length, 1.1 mm in apical diameter, and 1.2 mm in coronal diameter. Bone samples were collected at 5, 7, 14, 21, and 28 days after implant placement. A micro-quantitative computed tomography (QCT) system was used to scan these samples and a phantom in order to quantitate bone mineral measurements. Bone mineral density (BMD) of each sample was measured. Each sample was also examined by light microscopy after QCT imaging. At 14 and 28 days after implant placement, the bone-implant contact (BIC) ratios were calculated from light microscopy images and were divided into cortical bone and bone marrow regions. When BMD was compared between the osteoporosis and control groups using micro-QCT, the osteoporosis group had a significantly lower BMD in the region 0-20 µm from the implant surface in the bone marrow region at 14 days onward after implant placement. Compared with the control group, the osteoporosis model also had significantly lower BMD in all regions 0-100 µm from the implant surface in the bone marrow region at 14 days after placement. However, in the cortical bone region, no statistically significant difference was observed in the regions at the bone-implant interface. Light microscopy revealed osseointegration for all implants 28 days after implant placement. The osteoporosis model tended to have lower BICs compared with that of the control group, although this did not reach statistical significance. Our results showed that osseointegration was achieved in the osteoporosis model. However, the BMD was 30-40% lower than that of the control group in the region closest to the implant surface in bone marrow region. Peri-implant BMD was lower in a relatively large area in the osteoporosis model during an important time for osseointegration. Therefore, this result suggests that osteoporosis might be considered as a risk factor in implant therapy. The osteoporosis model had a lower BMD than the control group in the region closest to the implant during an important time for osseointegration. This result suggests that senile osteoporosis might be a risk factor in implant therapy. However, the osteoporosis model and the control group had no difference in peri-implant BMD in the cortical bone region. This suggests that risk might be avoided by implant placement that effectively uses the cortical bone. © 2011 Wiley Periodicals, Inc.

Increased Airway Wall Thickness is Associated with Adverse Longitudinal First-Second Forced Expiratory Volume Trajectories of Former World Trade Center workers.

PubMed

de la Hoz, Rafael E; Liu, Xiaoyu; Doucette, John T; Reeves, Anthony P; Bienenfeld, Laura A; Wisnivesky, Juan P; Celedón, Juan C; Lynch, David A; San José Estépar, Raúl

2018-05-24

Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of a quantitative computed tomography (QCT) imaging measurement of airway wall thickness, and other risk factors for adverse progression. We examined the trajectories of expiratory air flow decline in a group of 799 former WTC workers and volunteers with QCT-measured (with two independent systems) wall area percent (WAP) and at least 3 periodic spirometries. We calculated individual regression lines for first-second forced expiratory volume (FEV 1 ), identified subjects with rapidly declining and increasing ("gainers"), and compared them to subjects with normal and "stable" FEV 1 decline. We used multivariate logistic regression to model decliner vs. stable trajectories. The mean longitudinal FEV 1 slopes for the entire study population, and its stable, decliner, and gainer subgroups were, respectively, - 35.8, - 8, - 157.6, and + 173.62 ml/year. WAP was associated with "decliner" status (OR adj 1.08, 95% CI 1.02, 1.14, per 5% increment) compared to stable. Age, weight gain, baseline FEV 1 percent predicted, bronchodilator response, and pre-WTC occupational exposures were also significantly associated with accelerated FEV 1 decline. Analyses of gainers vs. stable subgroup showed WAP as a significant predictor in unadjusted but not consistently in adjusted analyses. The apparent normal age-related rate of FEV 1 decline results from averaging widely divergent trajectories. WAP is significantly associated with accelerated air flow decline in WTC workers.

Does metaphyseal cement augmentation in fracture management influence the adjacent subchondral bone and joint cartilage?: an in vivo study in sheep stifle joints.

PubMed

Goetzen, Michael; Hofmann-Fliri, Ladina; Arens, Daniel; Zeiter, Stephan; Stadelmann, Vincent; Nehrbass, Dirk; Richards, R Geoff; Blauth, Michael

2015-01-01

Augmentation of implants with polymethylmethacrylate (PMMA) bone cement in osteoporotic fractures is a promising approach to increase implant purchase. Side effects of PMMA for the metaphyseal bone, particularly for the adjacent subchondral bone plate and joint cartilage, have not yet been studied. The following experimental study investigates whether subchondral PMMA injection compromises the homeostasis of the subchondral bone and/or the joint cartilage.Ten mature sheep were used to simulate subchondral PMMA injection. Follow-ups of 2 (4 animals) and 4 (6 animals) months were chosen to investigate possible cartilage damage and subchondral plate alterations in the knee. Evaluation was completed by means of high-resolution peripheral quantitative computed tomography (HRpQCT) imaging, histopathological osteoarthritis scoring, and determination of glycosaminoglycan content in the joint cartilage. Results were compared with the untreated contralateral knee and statistically analyzed using nonparametric tests.Evaluation of the histological osteoarthritis score revealed no obvious cartilage damage for the treated knee; median histological score after 2 months 0 (range 4), after 4 months 1 (range 5). There was no significant difference when compared with the untreated control site after 2 and 4 months (P = 0.23 and 0.76, respectively). HRpQCT imaging showed no damage to the metaphyseal trabeculae. Glycosaminoglycan measurements of the treated joint cartilage after 4 months revealed no significant difference compared with the untreated cartilage (P = 0.24).The findings of this study support initial clinical observation that PMMA implant augmentation of metaphyseal fractures appears to be a safe procedure for fixation without harming the subchondral bone plate and adjacent joint cartilage.

Lower Trabecular Volumetric BMD at Metaphyseal Regions of Weight-Bearing Bones is Associated With Prior Fracture in Young Girls

PubMed Central

Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

2011-01-01

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research. PMID:20721933

LRP5 gene polymorphism and cortical bone

PubMed Central

Lauretani, Fulvio; Cepollaro, Chiara; Bandinelli, Stefania; Cherubini, Antonio; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Corsi, Anna Maria; Ceda, Gian Paolo; Brandi, Maria Luisa; Ferrucci, Luigi

2016-01-01

Background and aims There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro-architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Val667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. Methods We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21–94 yrs). Trabecular vBMD (vBMDt, mg/cm3), cortical vBMD (vBMDc, mg/cm3), cortical bone area (CBA, mm2) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Val667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. Conclusion These findings suggest that both Ala1330Val and Val667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women. PMID:21116122

A longitudinal study of trunk muscle properties and severity of thoracic kyphosis in women and men: The Framingham Study.

PubMed

Lorbergs, Amanda L; Allaire, Brett T; Yang, Laiji; Kiel, Douglas P; Cupples, L Adrienne; Jarraya, Mohamed; Guermazi, Ali; Travison, Thomas G; Bouxsein, Mary L; Anderson, Dennis E; Samelson, Elizabeth J

2018-04-24

Cross-sectional studies suggest that trunk muscle morphology in the lumbar spine is an important determinant of kyphosis severity in older adults. The contribution of age-related changes in muscle morphology in the thoracic and lumbar spine to progression of kyphosis is not known. Our objective was to determine cross-sectional and longitudinal associations of thoracic and lumbar muscle size and density with kyphosis. Participants were 1,087 women and men (mean age 61y) of the Framingham Heart Study who underwent baseline and follow-up quantitative computed tomography (QCT) scanning 6y apart. We used QCT scans to measure trunk muscle cross-sectional area (CSA, cm2) and density (HU) at the thoracic and lumbar spine and Cobb angle (degrees) from T4 to T12. Linear regression models estimated the association between muscle morphology and kyphosis. At baseline, smaller muscle CSA and lower density of thoracic (but not lumbar) spine muscles were associated with a larger (worse) Cobb angle in women and men. For example, each standard deviation (SD) decrease in baseline thoracic paraspinal muscle CSA was associated with a larger baseline Cobb angle in women (3.7°, 95%CI:2.9, 4.5) and men (2.5°, 95%CI:1.6, 3.3). Longitudinal analyses showed that loss of muscle CSA and density at the thoracic and lumbar spine was not associated with progression of kyphosis. Our findings suggest that kyphosis severity is related to smaller and lower density trunk muscles at the thoracic spine. Future studies are needed to determine how strengthening mid-back musculature alters muscle properties and contributes to preventing kyphosis progression.

Quantifying Leisure Physical Activity and Its Relation to Bone Density and Strength

PubMed Central

SHEDD, KRISTINE M.; HANSON, KATHY B.; ALEKEL, D. LEE; SCHIFERL, DANIEL J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2010-01-01

Purpose Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Methods Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. Results UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength–strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Conclusion Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss. PMID:18046190

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PubMed Central

Gourlay, Margaret L.; Specker, Bonny L.; Li, Chenxi; Hammett-Stabler, Catherine A.; Renner, Jordan B.; Rubin, Janet E.

2011-01-01

Purpose Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. Methods We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Results: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β= −0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. Conclusions After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight. PMID:22086136

Quantifying leisure physical activity and its relation to bone density and strength.

PubMed

Shedd, Kristine M; Hanson, Kathy B; Alekel, D Lee; Schiferl, Daniel J; Hanson, Laura N; Van Loan, Marta D

2007-12-01

Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength-strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss.

Normal Bone Microstructure and Density But Worse Physical Function in Older Women Treated with Selective Serotonin Reuptake Inhibitors, a Cross-Sectional Population-Based Study.

PubMed

Larsson, Berit; Mellström, Dan; Johansson, Lisa; Nilsson, Anna G; Lorentzon, Mattias; Sundh, Daniel

2018-05-05

Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7 ± 1.5 years) were included. Validated questionnaires were used to assess information regarding medical history, medications, smoking, mental and physical health, and physical activity. Physical function was measured using clinically used tests: timed up and go, walking speed, grip strength, chair stand test, and one leg standing. Bone mineral density (BMD) was measured at the hip and spine with dual-energy X-ray absorptiometry (Hologic Discovery A). Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT). Treatment with SSRIs was associated with higher BMD at the femoral neck, total hip, and lumbar spine, whereas no associations were found for any HR-pQCT-derived measurements. The use of SSRIs was associated with lower grip strength, walking speed, and fewer chair stand rises. These associations were valid also after adjustments for known risk factors for falls. Treatment with SSRIs was, independently of covariates, associated with worse physical function without any signs of inferior bone geometry and microstructure.

Bone mineral density in anorexia nervosa: Only weight and menses recovery?

PubMed

Jáuregui-Lobera, Ignacio; Bolaños-Ríos, Patricia; Sabaté, Juan

2016-11-01

The study objectives were to analyze the presence of reduced bone mass in a sample of patients with anorexia nervosa (AN) and amenorrhea, to assess Bone Mineral Density (BMD) recovery after having a normal weight is reached and regular menses are resumed, and to predict BMD after a treatment period considering different variables (baseline BMD, baseline and final body mass index (BMI), treatment duration). 35 patients with AN (mean age 20.57±5.77) were studied at treatment start (T 0 ) and after they had recovered their normal weight and regular menses (T 1 ) in order to measure their BMD using quantitative computed tomography (QCT) of the lumbar spine (L2-L4). At T 0 , 2.86% of patients had normal BMD, while a reduced bone mass consistent with osteopenia or with osteoporosis was found in 22.86% and 74.28% of patients respectively. At T 1 , the percentages were 20%, 20%, and 60% respectively. No significant differences were seen in L2-L3 and mean BMD (L2-L4). A significant difference was however found for L4 (p<0.05). A positive relationship was seen between final body mass index (BMI) and final BMD in patients with T 0 -T 1 >11 months, but not when the time period was ≤11 months. This follow-up study of changes not only in BMD but also in BMI and recovery of menses has clinical relevance from the viewpoint of the day-by-day treatment process. Use of QCT makes the study more relevant because this is a more advanced technique that allows for differentiating trabecular and cortical bone. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Lower trabecular volumetric BMD at metaphyseal regions of weight-bearing bones is associated with prior fracture in young girls.

PubMed

Farr, Joshua N; Tomás, Rita; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

2011-02-01

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump-In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual-energy X-ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1-1.9) and 1.3 (1.0-1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. Copyright © 2011 American Society for Bone and Mineral Research.

Voxel size dependency, reproducibility and sensitivity of an in vivo bone loading estimation algorithm

PubMed Central

Christen, Patrik; Schulte, Friederike A.; Zwahlen, Alexander; van Rietbergen, Bert; Boutroy, Stephanie; Melton, L. Joseph; Amin, Shreyasee; Khosla, Sundeep; Goldhahn, Jörg; Müller, Ralph

2016-01-01

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous. PMID:26790999

Cortical Matrix Mineral Density Measured Non-invasively in Pre- and Postmenopausal Women and a Woman with Vitamin D Dependent Rickets.

PubMed

Chiang, Cherie Y; Zebaze, Roger; Wang, Xiao-Fang; Ghasem-Zadeh, Ali; Zajac, Jeffrey D; Seeman, Ego

2018-02-28

Reduced bone mineral density (BMD) may be due to reduced mineralized bone matrix volume, incomplete secondary mineralization or reduced primary mineralization. As bone biopsy is invasive, we hypothesized that non-invasive image acquisition at high resolution can accurately quantify matrix mineral density (MMD). Quantification of MMD was confined to voxels attenuation photons above 80% of that produced by fully mineralized bone matrix because attenuation at this level is due to variation in mineralization not porosity. To assess accuracy, 9 cadaveric distal radii were imaged at a voxel size of 82 microns using high resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT, Scanco Medical AG, Switzerland) and compared with VivaCT 40 (µCT) at 19 microns voxel size. Associations between MMD and porosity were studied in 94 heathy vitamin D replete pre-menopausal, 77 post-menopausal women, and in a 27 year-old woman with vitamin-D Dependent Rickets (VDDR). Microstructure and MMD were quantified using StrAx (StraxCorp, Melbourne, Australia). MMD measured by HR-pQCT and µCT correlated (R = 0.87; p <0.0001). The precision error for MMD was 2.43%. Cortical porosity and MMD were associated with age (r 2  = 0.5 and - 0.4 respectively) and correlated inversely in pre- and post-menopausal women (both r 2  = 0.9, all p < 0.001). Porosity was higher, and MMD was lower, in post- than in pre-menopausal women (porosity 40.3% ± 7.0 versus 34.7% ± 3.5 respectively, MMD 65.4% ± 1.8 versus 66.6% ± 1.4 respectively, both p < 0.001). In the woman with VDDR, MMD was 5.6 SD lower, and porosity was 5.6 SD higher, than the respective trait means in premenopausal women. BMD was reduced (Z scores femoral neck - 4.3 SD, lumbar spine - 3.8 SD). Low radiation HR-pQCT may facilitate non-invasive quantification of bone's MMD and microstructure in health, disease and during treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats.

PubMed

Svensson, J; Lall, S; Dickson, S L; Bengtsson, B A; Rømer, J; Ahnfelt-Rønne, I; Ohlsson, C; Jansson, J O

2000-06-01

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0.5 mg/kg per day; n=7), GHRP-6 (0.5 mg/kg per day; n=8), GH (3.5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

Assessment of bone quality within the tuberosities of the osteoporotic humeral head: relevance for anchor positioning in rotator cuff repair.

PubMed

Kirchhoff, Chlodwig; Braunstein, Volker; Milz, Stefan; Sprecher, Christoph M; Fischer, Florian; Tami, Andrea; Ahrens, Philipp; Imhoff, Andreas B; Hinterwimmer, Stefan

2010-03-01

Tears of the rotator cuff are highly prevalent in patients older than 60 years, thereby presenting a population also suffering from osteopenia or osteoporosis. Suture fixation in the bone depends on the holding strength of the anchoring technique, whether a bone tunnel or suture anchor is selected. Because of osteopenic or osteoporotic bone changes, suture anchors in the older patient might pull out, resulting in failure of repair. The aim of our study was to analyze the bone quality within the tuberosities of the osteoporotic humeral head using high-resolution quantitative computed tomography (HR-pQCT). Descriptive laboratory study. Thirty-six human cadaveric shoulders were analyzed using HR-pQCT. The mean bone volume to total volume (BV/TV) as well as trabecular bone mineral densities (trabBMDs) of the greater tuberosity (GT) and the lesser tuberosity (LT) were determined. Within the GT, 6 volumes of interest (VOIs) within the LT, and 2 VOIs and 1 control volume within the subchondral area beyond the articular surface were set. Comparing BV/TV of the medial and the lateral row, significantly higher values were found medially (P < .001). The highest BV/TV, 0.030% + or - 0.027%, was found in the posteromedial portion of the GT (P < .05). Regarding the analysis of the LT, no difference was found comparing the superior (BV/TV: 0.024% + or - 0.022%) and the inferior (BV/TV: 0.019% + or - 0.016%) portion. Analyzing trabBMD, equal proportions were found. An inverse correlation with a correlation coefficient of -0.68 was found regarding BV/TV of the posterior portion of the GT and age (P < .05). Significant regional differences of trabecular microarchitecture were found in our HR-pQCT study. The volume of highest bone quality resulted for the posteromedial aspect of the GT. Moreover, a significant correlation of bone quality within the GT and age was found, while the bone quality within the LT seems to be independent from it. The shape of the rotator cuff tear largely determines the bony site of tendon reattachment, although the surgeon has distinct options to modify anchor positioning. According to our results, placement of suture anchors in a medialized way at the border to the articular surface might guarantee a better structural bone stock.

The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men

PubMed Central

Thomson, Wendy; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Gielen, Evelien; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A.; Bartfai, Gyorgy; Casanueva, Felipe; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Labrie, Fernand; Lean, Michael E. J.; Pendleton, Neil; Punab, Margus; Wu, Frederick C. W.; O'Neill, Terence W.

2011-01-01

Purpose Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40–79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. PMID:21760950

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Anti-inflammatory Potential of Quercetin-3-O-β-D-("2"-galloyl)-glucopyranoside and Quercetin Isolated from Diospyros kaki calyx via Suppression of MAP Signaling Molecules in LPS-induced RAW 264.7 Macrophages.

PubMed

Cho, Yong-Hun; Kim, Na-Hyung; Khan, Imran; Yu, Jae Myo; Jung, Hyun Gug; Kim, Han Hyuk; Jang, Jae Yoon; Kim, Hyeon Jeong; Kim, Dong-In; Kwak, Jae-Hoon; Kang, Sun Chul; An, Bong Jeun

2016-10-01

Diospyros kaki (DK) contains an abundance of flavonoids and has been used in folk medicine in Korea for centuries. Here, we report for the first time the anti-inflammatory activities of Quercetin (QCT) and Quercetin 3-O-β-("2"-galloyl)-glucopyranoside (Q32G) isolated from DK. We have determine the no cytotoxicity of Q32G and QCT against RAW 264.7 cells up to concentration of 50 μM. QCT and Q32G demonstrated potent anti-inflammatory activities by reducing expression of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and mitogen-activated protein kinase (MAPKs) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Both QCT or Q32G could decrease cellular protein levels of COX-2 and iNOS as well as secreted protein levels of NO, PGE 2 , and cytokines (TNF-α, IL-1β, and IL-6) in culture medium of LPS-stimulated RAW 264.7 macrophages. Immunoblot analysis showed that QCT and Q32G suppressed LPS-induced MAP kinase pathway proteins p-p38, ERK, and JNK. This study revealed that QCT and Q32G have anti-inflammatory potential, however Q32G possess comparable activity as that of QCT and could be use as adjuvant to treat inflammatory diseases. © 2016 Institute of Food Technologists®.

Frailty syndrome and skeletal muscle: results from the Invecchiare in Chianti study.

PubMed

Cesari, Matteo; Leeuwenburgh, Christiaan; Lauretani, Fulvio; Onder, Graziano; Bandinelli, Stefania; Maraldi, Cinzia; Guralnik, Jack M; Pahor, Marco; Ferrucci, Luigi

2006-05-01

Frailty is a common condition in elders and identifies a state of vulnerability for adverse health outcomes. Our objective was to provide a biological face validity to the well-established definition of frailty proposed by Fried et al. Data are from the baseline evaluation of 923 participants aged > or =65 y enrolled in the Invecchiare in Chianti study. Frailty was defined by the presence of > or =3 of the following criteria: weight loss, exhaustion, low walking speed, low hand grip strength, and physical inactivity. Muscle density and the ratios of muscle area and fat area to total calf area were measured by using a peripheral quantitative computerized tomography (pQCT) scan. Analyses of covariance and logistic regressions were performed to evaluate the relations between frailty and pQCT measures. The mean age (+/-SD) of the study sample was 74.8 +/- 6.8 y, and 81 participants (8.8%) had > or =3 frailty criteria. Participants with no frailty criteria had significantly higher muscle density (71.1 mg/cm(3), SE = 0.2) and muscle area (71.2%, SE = 0.4) than did frail participants (69.8 mg/cm(3), SE = 0.4; and 68.7%, SE = 1.1, respectively). Fat area was significantly higher in frail participants (22.0%, SE = 0.9) than in participants with no frailty criteria (20.3%, SE = 0.4). Physical inactivity and low walking speed were the frailty criteria that showed the strongest associations with pQCT measures. Frail subjects, identified by an easy and inexpensive frailty score, have lower muscle density and muscle mass and higher fat mass than do nonfrail persons.

Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers.

PubMed

Patra, Arjun; Satpathy, Swaha; Shenoy, Anitha K; Bush, Jason A; Kazi, Mohsin; Hussain, Muhammad Delwar

2018-01-01

Quercetin (QCT), a naturally occurring flavonoid has a wide array of pharmacological properties such as anticancer, antioxidant and anti-inflammatory activities. QCT has low solubility in water and poor bioavailability, which limited its use as a therapeutic molecule. Polymeric micelles (PMs) is a novel drug delivery system having characteristics like smaller particle size, higher drug loading, sustained drug release, high stability, increased cellular uptake and improved therapeutic potential. In the present study, we have formulated and characterized mixed PMs (MPMs) containing QCT for increasing its anticancer potential. The MPMs were prepared by thin film hydration method, and their physicochemical properties were characterized. The in vitro anticancer activity of the MPMs were tested in breast (MCF-7 and MDA-MB-231, epithelial and metastatic cancer cell lines, respectively), and ovarian (SKOV-3 and NCI/ADR, epithelial and multi-drug resistant cell lines, respectively) cancer. The optimal MPM formulations were obtained from Pluronic polymers, P123 and P407 with molar ratio of 7:3 (A16); and P123, P407 and TPGS in the molar ratio of 7:2:1 (A22). The size of the particles before lyophilization (24.83±0.44 nm) and after lyophilisation (37.10±4.23 nm), drug loading (8.75±0.41%), and encapsulation efficiency (87.48±4.15%) for formulation A16 were determined. For formulation A22, the particle size before lyophilization, after lyophilization, drug loading and encapsulation efficiency were 26.37±2.19 nm, 45.88±13.80 nm, 9.01±0.11% and 90.07±1.09%, respectively. The MPMs exhibited sustained release of QCT compared to free QCT as demonstrated from in vitro release experiments. The solubility of QCT was markedly improved compared to pure QCT. The MPMs were highly stable in aqueous media as demonstrated by their low critical micelle concentration. The concentration which inhibited 50% growth (IC 50 ) values of both micellar preparations in all the cancer cell lines were significantly less compared to free QCT. Both the MPMs containing QCT could be used for effective delivery to different type of cancer and may be considered for further development.

Physiologically based pharmacokinetic model for quinocetone in pigs and extrapolation to mequindox.

PubMed

Zhu, Xudong; Huang, Lingli; Xu, Yamei; Xie, Shuyu; Pan, Yuanhu; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

2017-02-01

Physiologically based pharmacokinetic (PBPK) models are scientific methods used to predict veterinary drug residues that may occur in food-producing animals, and which have powerful extrapolation ability. Quinocetone (QCT) and mequindox (MEQ) are widely used in China for the prevention of bacterial infections and promoting animal growth, but their abuse causes a potential threat to human health. In this study, a flow-limited PBPK model was developed to simulate simultaneously residue depletion of QCT and its marker residue dideoxyquinocetone (DQCT) in pigs. The model included compartments for blood, liver, kidney, muscle and fat and an extra compartment representing the other tissues. Physiological parameters were obtained from the literature. Plasma protein binding rates, renal clearances and tissue/plasma partition coefficients were determined by in vitro and in vivo experiments. The model was calibrated and validated with several pharmacokinetic and residue-depletion datasets from the literature. Sensitivity analysis and Monte Carlo simulations were incorporated into the PBPK model to estimate individual variation of residual concentrations. The PBPK model for MEQ, the congener compound of QCT, was built through cross-compound extrapolation based on the model for QCT. The QCT model accurately predicted the concentrations of QCT and DQCT in various tissues at most time points, especially the later time points. Correlation coefficients between predicted and measured values for all tissues were greater than 0.9. Monte Carlo simulations showed excellent consistency between estimated concentration distributions and measured data points. The extrapolation model also showed good predictive power. The present models contribute to improve the residue monitoring systems of QCT and MEQ, and provide evidence of the usefulness of PBPK model extrapolation for the same kinds of compounds.

Genotoxicity of quinocetone, cyadox and olaquindox in vitro and in vivo.

PubMed

Ihsan, Awais; Wang, Xu; Zhang, Wei; Tu, Honggang; Wang, Yulian; Huang, Lingli; Iqbal, Zahid; Cheng, Guyue; Pan, Yuanhu; Liu, Zhenli; Tan, Ziqiang; Zhang, Yuanyuan; Yuan, Zonghui

2013-09-01

Quinocetone (QCT) and Cyadox (CYA) are important derivative of heterocyclic N-oxide quinoxaline (QdNO), used actively as antimicrobial feed additives in China. Here, we tested and compared the genotoxic potential of QCT and CYA with olaquindox (OLA) in Ames test, HGPRT gene mutation (HGM) test in V79 cells, unscheduled DNA synthesis (UDS) assay in human peripheral lymphocytes, chromosome aberration (CA) test, and micronucleus (MN) test in mice bone marrow. OLA was found genotoxic in all 5 assays. In Ames test, QCT produced His(+) mutants at 6.9 μg/plate in Salmonella typhimurium TA 97, at 18.2 μg/plate in TA 100, TA 1535, TA 1537, and at 50 μg/plate in TA 98. CYA produced His(+) mutants at 18.2 μg/plate in TA 97, TA 1535, and at 50 μg/plate in TA 98, TA 100 and TA 1537. QCT was found positive in HGM and UDS assay at concentrations ≥10 μg/ml while negative results were reported in CA test and MN test. Collectively, we found that OLA was more genotoxic than QCT and CYA. Genotoxicity of QCT was found at higher concentration levels in Ames test, HGM and UDS assays while CYA showed weak mutagenic potential to bacterial cells in Ames test. Copyright © 2013 Elsevier Ltd. All rights reserved.

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients

PubMed Central

Hui, Susanta K; Arentsen, Luke; Sueblinvong, Thanasak; Brown, Keenan; Bolan, Pat; Ghebre, Rahel G; Downs, Levi; Shanley, Ryan; Hansen, Karen E.; Minenko, Anne G.; Takhashi, Yutaka; Yagi, Masashi; Zhang, Yan; Geller, Melissa; Reynolds, Margaret; Lee, Chung K; Blaes, Anne H.; Allen, Sharon; Zobel, Bruno Beomonte; Le, Chap; Froelich, Jerry; Rosen, Clifford; Yee, Douglas

2014-01-01

Purpose Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. Methods We validated DECT in pre-clinical and Phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in cadaver vertebrae and compared with DECT and WF-MRI. For a Phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12 months after treatment. BMD and MF percent and distribution were quantified in lumbar vertebrae and the right femoral neck. Results Measured precision (3 mg/cm3) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r = 0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r = 0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only by 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Conclusion Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy. PMID:25536285

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

PubMed

Hui, Susanta K; Arentsen, Luke; Sueblinvong, Thanasak; Brown, Keenan; Bolan, Pat; Ghebre, Rahel G; Downs, Levi; Shanley, Ryan; Hansen, Karen E; Minenko, Anne G; Takhashi, Yutaka; Yagi, Masashi; Zhang, Yan; Geller, Melissa; Reynolds, Margaret; Lee, Chung K; Blaes, Anne H; Allen, Sharon; Zobel, Bruno Beomonte; Le, Chap; Froelich, Jerry; Rosen, Clifford; Yee, Douglas

2015-04-01

Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative Effects of Teriparatide and Risedronate in Glucocorticoid-Induced Osteoporosis in Men: 18-Month Results of the EuroGIOPs Trial

PubMed Central

Glüer, Claus-C; Marin, Fernando; Ringe, Johann D; Hawkins, Federico; Möricke, Rüdiger; Papaioannu, Nikolaos; Farahmand, Parvis; Minisola, Salvatore; Martínez, Guillermo; Nolla, Joan M; Niedhart, Christopher; Guañabens, Nuria; Nuti, Ranuccio; Martín-Mola, Emilio; Thomasius, Friederike; Kapetanos, Georgios; Peña, Jaime; Graeff, Christian; Petto, Helmut; Sanz, Beatriz; Reisinger, Andreas; Zysset, Philippe K

2013-01-01

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate. PMID:23322362

Early Changes of the Cortical Micro-Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis.

PubMed

Werner, David; Simon, David; Englbrecht, Matthias; Stemmler, Fabian; Simon, Christoph; Berlin, Andreas; Haschka, Judith; Renner, Nina; Buder, Thomas; Engelke, Klaus; Hueber, Axel J; Rech, Jürgen; Schett, Georg; Kleyer, Arnd

2017-08-01

To characterize the specific structural properties of the erosion-prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA). In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral quantitative computed tomography (HR-pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution. Investigation by HR-pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P < 0.001), with 20-49-year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion-prone radial side of the joint. CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA. © 2017, American College of Rheumatology.

A GPU-based symmetric non-rigid image registration method in human lung.

PubMed

Haghighi, Babak; D Ellingwood, Nathan; Yin, Youbing; Hoffman, Eric A; Lin, Ching-Long

2018-03-01

Quantitative computed tomography (QCT) of the lungs plays an increasing role in identifying sub-phenotypes of pathologies previously lumped into broad categories such as chronic obstructive pulmonary disease and asthma. Methods for image matching and linking multiple lung volumes have proven useful in linking structure to function and in the identification of regional longitudinal changes. Here, we seek to improve the accuracy of image matching via the use of a symmetric multi-level non-rigid registration employing an inverse consistent (IC) transformation whereby images are registered both in the forward and reverse directions. To develop the symmetric method, two similarity measures, the sum of squared intensity difference (SSD) and the sum of squared tissue volume difference (SSTVD), were used. The method is based on a novel generic mathematical framework to include forward and backward transformations, simultaneously, eliminating the need to compute the inverse transformation. Two implementations were used to assess the proposed method: a two-dimensional (2-D) implementation using synthetic examples with SSD, and a multi-core CPU and graphics processing unit (GPU) implementation with SSTVD for three-dimensional (3-D) human lung datasets (six normal adults studied at total lung capacity (TLC) and functional residual capacity (FRC)). Success was evaluated in terms of the IC transformation consistency serving to link TLC to FRC. 2-D registration on synthetic images, using both symmetric and non-symmetric SSD methods, and comparison of displacement fields showed that the symmetric method gave a symmetrical grid shape and reduced IC errors, with the mean values of IC errors decreased by 37%. Results for both symmetric and non-symmetric transformations of human datasets showed that the symmetric method gave better results for IC errors in all cases, with mean values of IC errors for the symmetric method lower than the non-symmetric methods using both SSD and SSTVD. The GPU version demonstrated an average of 43 times speedup and ~5.2 times speedup over the single-threaded and 12-threaded CPU versions, respectively. Run times with the GPU were as fast as 2 min. The symmetric method improved the inverse consistency, aiding the use of image registration in the QCT-based evaluation of the lung.

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

NASA Technical Reports Server (NTRS)

Whalen, R.

1999-01-01

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.

Epistatic Effects Contribute to Variation in BMD in Fischer 344 × Lewis F2 Rats

PubMed Central

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. Introduction The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F2 progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Materials and Methods Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an α level of 0.01. Results and Conclusions Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture. PMID:17907919

Epistatic effects contribute to variation in BMD in Fischer 344 x Lewis F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

To further delineate the factors underlying the complex genetic architecture of BMD in the rat model, a genome screen for epistatic interactions was conducted. Several significant interactions were identified, involving both previously identified and novel QTLs. The variation in several of the risk factors for osteoporotic fracture, including BMD, has been shown to be caused largely by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We have previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 595 female F(2) progeny of Fischer 344 and Lewis rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted BMD (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine a genome-wide significance threshold for the epistasis or interaction LOD score corresponding to an alpha level of 0.01. Novel loci on chromosomes 12 and 15 showed a strong epistatic effect on total BMD at the femoral midshaft by pQCT (LOD = 5.4). A previously reported QTL on chromosome 7 was found to interact with a novel locus on chromosome 20 to affect whole lumbar BMD by pQCT (LOD = 6.2). These results provide new information regarding the mode of action of previously identified rat QTLs, as well as identifying novel loci that act in combination with known QTLs or with other novel loci to contribute to the risk factors for osteoporotic fracture.

Classical Dynamics of State-Resolved Hyperthermal O(3P) + H2O(1A1) (Pre-Print)

DTIC Science & Technology

2012-10-01

lower velocities, over two orders of magnitude at 4 Distribution A: Approved for public release; distribution unlimited. 15 km s -1 , in going from...QCT EM mode energy, mentioned earlier. The present QCT ACT and QCT HA results with ZP1 and GB0 are within a factor of two or three of the...for the J=1 level, where the standard classical results overestimate the quantum cross sections by a little over a factor of two . Although they do

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

PubMed

Karasik, David; Demissie, Serkalem; Lu, Darlene; Broe, Kerry E; Boyd, Steven K; Liu, Ching-Ti; Hsu, Yi-Hsiang; Bouxsein, Mary L; Kiel, Douglas P

2017-11-01

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h 2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h 2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h 2 results, but adjustment for aBMD at the UD and FN somewhat decreased h 2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ P  = 0.826, ρ G  = 0.954, respectively), whereas environmental correlations were lower (ρ E  = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ P  = 0.577, ρ G  = 0.703, both p < 0.001; ρ E  = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Bone Density and Structure in Long-Term Survivors of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Mostoufi-Moab, Sogol; Ginsberg, Jill P.; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B.

2015-01-01

Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5–26 years, a median of 7 (range 3–16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (−1.21 ± 1.25 vs. 0.23 ± 0.92; p<0.001), vs. reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD [−1.05 (95% CI −1.33, −0.78), p<0.001], cortical Zp [−0.63 (−0.91, −0.35), p<0.001], and muscle [−1.01 (−1.30, −0.72), p<0.001] Z-scores and greater fat [0.82 (0.54,1.11), p<0.001] Z-scores, vs. reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (−1.30 ± 1.40 vs. −0.49 ± 0.88; p=0.01) and muscle (−1.34 ± 1.42 vs. −0.34 ± 0.87; p<0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (−1.64 ± 2.47 vs. −0.28 ± 1.24; p=0.05); however, muscle differences were not significant (−1.69 ± 1.84 vs. −0.78 ± 1.01; p=0.09). History of graft vs. host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture implications of these deficits, and to identify therapies to improve bone accrual following alloHSCT during childhood. PMID:22189761

Protective Effect of Quercetin on Melphalan-Induced Oxidative Stress and Impaired Renal and Hepatic Functions in Rat

PubMed Central

Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

2014-01-01

One major challenge with the use of anticancer agents is the phenomenon of drug-induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while quercetin (QCT) is an antioxidant. We investigated the protective role of quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160–170 g) were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%, and 188%, respectively (P < 0.05). Similarly, plasma ALP, ALT, AST, and γ-GT activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%, respectively, relative to control. However, pre or cotreatment with QCT ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic acid and GSH and activities of glutathione-S-transferase, SOD, and catalase decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively, followed by increase in MDA content by 46.5% relative to control. Pre- and cotreatment with QCT reestablished the hepatic antioxidant status and lipid peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic toxicity in rats. PMID:25574394

Effects of whole body vibration exercises on bone mineral density of women with postmenopausal osteoporosis without medications: novel findings and literature review

PubMed Central

Dionello, C.F.; Sá-Caputo, D.; Pereira, H.V.F.S.; Sousa-Gonçalves, C.R.; Maiworm, A.I.; Morel, D.S.; Moreira-Marconi, E.; Paineiras-Domingos, L.L.; Bemben, D.; Bernardo-Filho, M.

2016-01-01

Objectives: The aim of this study was to review the literature about the effect of whole body vibration exercise in the BMD in patients with postmenopausal osteoporosis without medications. Methods: A systematic review was performed. Results: The frequency of the mechanical vibration used in the protocols has varied from 12 to 90 Hz. The time used in the protocols varied from 2 up to 22 months. Techniques with X-rays were used in nine of the twelve publications analyzed, the Dual energy X-ray absorptiometry (DEXA) in eight studies and the High resolution peripheral quantitative computed tomography (HR-pQCT) in one publication. The concentration of some biomarkers was determined, as the sclerostin, the bone alkaline phosphatase, N-telopeptide X and 25-hydroxyvitamin D. Among the twelve articles analyzed, seven of them have shown an improvement of the BMD of some bone of postmenopausal women exposed to whole body vibration exercises not associated to medications; as well as modifications in biomarkers. PMID:27609034

Hypergravity suppresses bone resorption in ovariectomized rats

NASA Astrophysics Data System (ADS)

Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

2011-04-01

The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhao, Jing; Liu, Juan; Wei, Tuo; Ma, Xiaowei; Cheng, Qiang; Huo, Shuaidong; Zhang, Chunqiu; Zhang, Yanan; Duan, Xianglin; Liang, Xing-Jie

2016-02-01

Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration-resistant prostate cancer'' (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL-1, which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 μM) of M-QCTs was much lower than free QCT (>200 μM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment.Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to ``castration-resistant prostate cancer'' (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL-1, which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 μM) of M-QCTs was much lower than free QCT (>200 μM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment. Electronic supplementary information (ESI) available: XRD and 1H NMR analysis of quercetin-loaded DSPE-PEG2000 micelles (M-QCTs); in vitro cytotoxicity of increasing concentrations of empty micelles (EMs) against PC-3 cells; hemolysis assay of empty micelles (EMs); representative images of H&E staining of various organs from mice with PC-3 cell xenografts after treatment with QCT or M-QCTs at a quercetin-equivalent dose of 30 mg kg-1 and the serum biochemistry analyses related to liver function and renal function after QCT or M-QCT treatment in PC-3 xenograft mice. See DOI: 10.1039/c5nr08966b

Bone geometry, volumetric bone mineral density, microarchitecture and estimated bone strength in Caucasian females with systemic lupus erythematosus. A cross-sectional study using HR-pQCT.

PubMed

Hansen, Stinus; Gudex, Claire; Åhrberg, Fabian; Brixen, Kim; Voss, Anne

2014-12-01

Patients with systemic lupus erythematosus (SLE) have an increased risk of fracture. We used high resolution peripheral quantitative computed tomography (HR-pQCT) to measure bone geometry, volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture and estimated bone strength by finite element analysis (FEA) at the distal radius and tibia to assess bone characteristics beyond BMD that may contribute to the increased risk of fracture. Thirty-three Caucasian women with SLE (median age 48, range 21-64 years) and 99 controls (median age 45, range 21-64 years) were studied. Groups were comparable in radius regarding geometry and vBMD, but SLE patients had lower trabecular number (-7%, p < 0.05), higher trabecular separation (13%, p < 0.05) and lower FEA-estimated failure load compared to controls (-10%, p < 0.05). In tibia, SLE patients had lower total vBMD (-11%, p < 0.01), cortical area (-14%, p < 0.001) and cortical thickness (-16%, p < 0.001) and higher trabecular area (8%, p < 0.05). In subgroup analyses of the premenopausal participants (SLE n = 21, controls n = 63), SLE patients had significantly lower trabecular bone volume fraction [(BV/TV); -17%, p < 0.01], trabecular number (-9%, p < 0.01), trabecular thickness (-9%, p < 0.05) and higher trabecular separation (13%, p < 0.01) and trabecular network inhomogeneity (14%, p < 0.05) in radius along with lower BV/TV (-15%, p < 0.01) and higher trabecular separation (11%, p < 0.05) in tibia. FEA-estimated bone strength was lower in both radius (-11%, p < 0.01) and tibia (-10%, p < 0.05). In conclusion, Caucasian women with SLE compared to controls had fewer and more widely separated trabeculae and lower estimated bone strength in radius and lower total vBMD, cortical area and thickness in tibia.

Long bone robustness during growth: A cross-sectional pQCT examination of children and young adults aged 5-29years.

PubMed

Rantalainen, Timo; Weeks, Benjamin K; Nogueira, Rossana C; Beck, Belinda R

2016-12-01

Skeletal robustness (cross-section size relative to length) is associated with stress fractures in adults, and appears to explain the high incidence of distal radius fractures in adolescents. However, little is known about the ontogeny of long bone robustness during the first three decades of life. Therefore, we explored the ontogeny of tibial, fibular, ulnar and radial robustness in a cross-sectional sample of 5 to 29year-old volunteers of both sexes. Peripheral quantitative computed tomography (pQCT) was used to evaluate cross-sections of the leg (4%, 14%, 38% and 66%), and forearm (4%, and 66%) in N=432 individuals. Robustness was evaluated as the total bone area divided by bone length. Differences between age-groups, sexes, and age-group×sex interactions were evaluated with ANOVA with Tukey's post hocs where appropriate. Most bone sites exhibited more robust bones in men than women (P<0.001 to 0.02), and in older age-groups than younger (P<0.001). Sex×age-group interaction was observed at the 66% and 38% tibia sites with robustness increasing more with age in men than in women (P=0.006 to 0.042). Post-hoc analyses indicated no sex differences prior to 13years-of-age, and notable exceptions to increasing robustness with age at the 4% radial and 66% tibial sites, which exhibited reduced robustness in age groups close to peak height velocity. In conclusion, the present results suggest that very little sexual dimorphism in long bone robustness exists prior to puberty, and that divergence occurs primarily after cessation of longitudinal growth. A period of relative diaphyseal slenderness was identified at age-groups coinciding with the adolescent growth spurt, which may be related to the relatively high incidence of frank and stress fracture in adolescents. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone strength estimates relative to vertical ground reaction force discriminates women runners with stress fracture history.

PubMed

Popp, Kristin L; McDermott, William; Hughes, Julie M; Baxter, Stephanie A; Stovitz, Steven D; Petit, Moira A

2017-01-01

To determine differences in bone geometry, estimates of bone strength, muscle size and bone strength relative to load, in women runners with and without a history of stress fracture. We recruited 32 competitive distance runners aged 18-35, with (SFX, n=16) or without (NSFX, n=16) a history of stress fracture for this case-control study. Peripheral quantitative computed tomography (pQCT) was used to assess volumetric bone mineral density (vBMD, mg/mm 3 ), total (ToA) and cortical (CtA) bone areas (mm 2 ), and estimated compressive bone strength (bone strength index; BSI, mg/mm 4 ) at the distal tibia. ToA, CtA, cortical vBMD, and estimated strength (section modulus; Zp, mm 3 and strength strain index; SSIp, mm 3 ) were measured at six cortical sites along the tibia. Mean active peak vertical (pkZ) ground reaction forces (GRFs), assessed from a fatigue run on an instrumented treadmill, were used in conjunction with pQCT measurements to estimate bone strength relative to load (mm 2 /N∗kg -1 ) at all cortical sites. SSIp and Zp were 9-11% lower in the SFX group at mid-shaft of the tibia, while ToA and vBMD did not differ between groups at any measurement site. The SFX group had 11-17% lower bone strength relative to mean pkZ GRFs (p<0.05). These findings indicate that estimated bone strength at the mid-tibia and mean pkZ GRFs are lower in runners with a history of stress fracture. Bone strength relative to load is also lower in this same region suggesting that strength deficits in the middle 1/3 of the tibia and altered gait biomechanics may predispose an individual to stress fracture. Copyright © 2016. Published by Elsevier Inc.

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

PubMed

DeBoer, Mark D; Lee, Arthur M; Herbert, Kirabo; Long, Jin; Thayu, Meena; Griffin, Lindsay M; Baldassano, Robert N; Denson, Lee A; Zemel, Babette S; Denburg, Michelle R; Herskovitz, Rita; Leonard, Mary B

2018-03-01

Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment.

PubMed

Shi, Lijie; Sánchez-Guijo, Alberto; Hartmann, Michaela F; Schönau, Eckhard; Esche, Jonas; Wudy, Stefan A; Remer, Thomas

2015-02-01

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1. © 2014 American Society for Bone and Mineral Research.

Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women

PubMed Central

Preisser, J. S.; Hammett-Stabler, C. A.; Renner, J. B.; Rubin, J.

2011-01-01

Summary The association between follicle-stimulating hormone (FSH) and bone density was tested in 111 postmenopausal women aged 50–64 years. In the multivariable analysis, weight and race were important determinants of bone mineral density. FSH, bioavailable estradiol, and other hormonal variables did not show statistically significant associations with bone density at any site. Introduction FSH has been associated with bone density loss in animal models and longitudinal studies of women. Most of these analyses have not considered the effect of weight or race. Methods We tested the association between FSH and bone density in younger postmenopausal women, adjusting for patient-related factors. In 111 postmenopausal women aged 50–64 years, areal bone mineral density (BMD) was measured at the lumbar spine, femoral neck, total hip, and distal radius using dual-energy X-ray absorptiometry, and volumetric BMD was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Height, weight, osteoporosis risk factors, and serum hormonal factors were assessed. Results FSH inversely correlated with weight, bioavailable estradiol, areal BMD at the lumbar spine and hip, and volumetric BMD at the ultradistal radius. In the multivariable analysis, no hormonal variable showed a statistically significant association with areal BMD at any site. Weight was independently associated with BMD at all central sites (p<0.001), but not with BMD or pQCT measures at the distal radius. Race was independently associated with areal BMD at all sites (p≤0.008) and with cortical area at the 33% distal radius (p=0.004). Conclusions Correlations between FSH and bioavailable estradiol and BMD did not persist after adjustment for weight and race in younger postmenopausal women. Weight and race were more important determinants of bone density and should be included in analyses of hormonal influences on bone. PMID:21125395

In Vivo Evaluation of Bulk Metallic Glasses for Osteosynthesis Devices

PubMed Central

Imai, Kazuhiro; Hiromoto, Sachiko

2016-01-01

Bulk metallic glasses (BMGs) show higher strength and lower Young’s modulus than Ti-6Al-4V alloy and SUS 316L stainless steel. This study aimed to perform in vivo evaluations of Zr65Al7.5Ni10Cu17.5 BMGs for osteosynthesis devices. In the study for intramedullary implants, osteotomies of the femoral bones were performed in male Wistar rats and were stabilized with Zr65Al7.5Ni10Cu17.5 BMGs, Ti-6Al-4V alloy, or 316L stainless steel intramedullary nails for 12 weeks. In the study for bone surface implants, Zr65Al7.5Ni10Cu17.5 BMGs ribbons were implanted on the femur surface for 6 weeks. Local effects on the surrounding soft tissues of the implanted BMGs were assessed by histological observation. Implanted materials’ surfaces were examined using scanning electron microscopy equipped with energy dispersive X-ray spectroscopy (SEM-EDS). In the study for intramedullary implants, bone healing after osteotomy was assessed by peripheral quantitative computed tomography (QCT) and mechanical tests. Histological observation showed no findings of the biological effects. SEM-EDS showed no noticeable change on the surface of BMGs, while Ca and P deposition was seen on the Ti-6Al-4V alloy surface, and irregularities were seen on the 316L stainless steel surface. Mechanical test and peripheral QCT showed that, although there was no significant difference, bone healing of BMGs was more than that of Ti-6Al-4V alloy. The results indicated that Zr-based BMGs can lead to bone healing equal to or greater than Ti-6Al-4V alloy. Zr-based BMGs exhibited the advantage of less bone bonding and easier implant removal compared with Ti-6Al-4V alloy. In conclusion, Zr-based BMGs are promising for osteosynthesis devices that are eventually removed. PMID:28773792

Multiscale Computational Analysis of Nitrogen and Oxygen Gas-Phase Thermochemistry in Hypersonic Flows

NASA Astrophysics Data System (ADS)

Bender, Jason D.

Understanding hypersonic aerodynamics is important for the design of next-generation aerospace vehicles for space exploration, national security, and other applications. Ground-level experimental studies of hypersonic flows are difficult and expensive; thus, computational science plays a crucial role in this field. Computational fluid dynamics (CFD) simulations of extremely high-speed flows require models of chemical and thermal nonequilibrium processes, such as dissociation of diatomic molecules and vibrational energy relaxation. Current models are outdated and inadequate for advanced applications. We describe a multiscale computational study of gas-phase thermochemical processes in hypersonic flows, starting at the atomic scale and building systematically up to the continuum scale. The project was part of a larger effort centered on collaborations between aerospace scientists and computational chemists. We discuss the construction of potential energy surfaces for the N4, N2O2, and O4 systems, focusing especially on the multi-dimensional fitting problem. A new local fitting method named L-IMLS-G2 is presented and compared with a global fitting method. Then, we describe the theory of the quasiclassical trajectory (QCT) approach for modeling molecular collisions. We explain how we implemented the approach in a new parallel code for high-performance computing platforms. Results from billions of QCT simulations of high-energy N2 + N2, N2 + N, and N2 + O2 collisions are reported and analyzed. Reaction rate constants are calculated and sets of reactive trajectories are characterized at both thermal equilibrium and nonequilibrium conditions. The data shed light on fundamental mechanisms of dissociation and exchange reactions -- and their coupling to internal energy transfer processes -- in thermal environments typical of hypersonic flows. We discuss how the outcomes of this investigation and other related studies lay a rigorous foundation for new macroscopic models for hypersonic CFD. This research was supported by the Department of Energy Computational Science Graduate Fellowship and by the Air Force Office of Scientific Research Multidisciplinary University Research Initiative.

Quasi-chemical theory of F-(aq): The "no split occupancies rule" revisited

NASA Astrophysics Data System (ADS)

Chaudhari, Mangesh I.; Rempe, Susan B.; Pratt, Lawrence R.

2017-10-01

We use ab initio molecular dynamics (AIMD) calculations and quasi-chemical theory (QCT) to study the inner-shell structure of F-(aq) and to evaluate that single-ion free energy under standard conditions. Following the "no split occupancies" rule, QCT calculations yield a free energy value of -101 kcal/mol under these conditions, in encouraging agreement with tabulated values (-111 kcal/mol). The AIMD calculations served only to guide the definition of an effective inner-shell constraint. QCT naturally includes quantum mechanical effects that can be concerning in more primitive calculations, including electronic polarizability and induction, electron density transfer, electron correlation, molecular/atomic cooperative interactions generally, molecular flexibility, and zero-point motion. No direct assessment of the contribution of dispersion contributions to the internal energies has been attempted here, however. We anticipate that other aqueous halide ions might be treated successfully with QCT, provided that the structure of the underlying statistical mechanical theory is absorbed, i.e., that the "no split occupancies" rule is recognized.

Multiscale and multimodality computed tomography for cortical bone analysis

NASA Astrophysics Data System (ADS)

Ostertag, A.; Peyrin, F.; Gouttenoire, P. J.; Laredo, J. D.; DeVernejoul, M. C.; Cohen Solal, M.; Chappard, C.

2016-12-01

In clinical studies, high resolution peripheral quantitative computed tomography (HR-pQCT) is used to separately evaluate cortical bone and trabecular bone with an isotropic voxel of 82 µm3, and typical cortical parameters are cortical density (D.comp), thickness (Ct.Th), and porosity (Ct.Po). In vitro, micro-computed tomography (micro-CT) is used to explore the internal cortical bone micro-structure with isotropic voxels and high resolution synchrotron radiation (SR); micro-CT is considered the ‘gold standard’. In 16 tibias and 8 femurs, HR-pQCT measurements were compared to conventional micro-CT measurements. To test modality effects, conventional micro-CT measurements were compared to SR micro-CT measurements at 7.5 µm3 SR micro-CT measurements were also tested at different voxel sizes for the femurs, specifically, 7.5 µm3 versus 2.8 µm3. D.comp (r  =  -0.88, p  <  10-3) was the parameter best correlated with porosity (Po.V/TV). The correlation was not affected by the removal of pores under 130 µm. Ct.Th was also significantly highly correlated (r  =  -0.89 p  <  10-3), while Ct.Po was correlated with its counterpart Po.V/TV (r  =  0.74, p  <  10-3). From SR micro-CT and conventional micro-CT at 7.5 µm3 in matching areas, Po.V/TV and pore diameter were underestimated in conventional micro-CT with mean  ±  standard deviation (SD) biases of  -2.5  ±  1.9% and  -0.08  ±  0.08 mm, respectively. In contrast, pore number (Po.N) and pore separation (Po.Sp) were overestimated with mean  ±  SD biases of  +0.03  ±  0.04 mm-1 and  +0.02  ±  0.04 mm, respectively. The results from the tibia and femur were similar when the results of SR micro-CT at 7.5 µm3 and 2.8 µm3 were compared. Po.V/TV, specific surface of pores (Po.S/Po.V), and Po.N were underestimated with mean biases of  -1.7  ±  0.9%, -4.6  ±  4.4 mm-1, and  -0.26  ±  0.15 mm-1, respectively. In contrast, pore spacing was overestimated at 7.5 µm3 compared to 2.8 µm3 with mean biases of 0.05  ±  0.03 mm. Cortical bone measurements from HR-pQCT images provided consistent results compared to those obtained using conventional micro-CT at the distal tibia. D.comp was highly correlated to Po.V/TV because it considers both the micro-porosity (Haversian systems) and macro-porosity (resorption lacunae) of cortical bone. The complexity of canal organization, (including shape, connectivity, and surface) are not fully considered in conventional micro-CT in relation to beam hardening and cone beam reconstruction artifacts. With the exception of Po.V/TV measurements, morphological and topological measurements depend on the characteristics of the x-ray beam, and to a lesser extent, on image resolution.

Application of low-tube current with iterative model reconstruction on Philips Brilliance iCT Elite FHD in the accuracy of spinal QCT using a European spine phantom.

PubMed

Wu, Yan; Jiang, Yaojun; Han, Xueli; Wang, Mingyue; Gao, Jianbo

2018-02-01

To investigate the repeatability and accuracy of quantitative CT (QCT) measurement of bone mineral density (BMD) by low-mAs using iterative model reconstruction (IMR) technique based on phantom model. European spine phantom (ESP) was selected and measured on the Philips Brilliance iCT Elite FHD machine for 10 times. Data were transmitted to the QCT PRO workstation to measure BMD (mg/cm 3 ) of the ESP (L1, L2, L3). Scanning method: the voltage of X-ray tube is 120 kV, the electric current of X-ray tube output in five respective groups A-E were: 20, 30, 40, 50 and 60 mAs. Reconstruction: all data were reconstructed using filtered back projection (FBP), IR levels of hybrid iterative reconstruction (iDose 4 , levels 1, 2, 3, 4, 5, 6 were used) and IMR (levels 1, 2, 3 were used). ROIs were placed in the middle of L1, L2 and L3 spine phantom in each group. CT values, noise and contrast-to-noise ratio (CNR) were measured and calculated. One-way analysis of variance (ANOVA) was used to compare BMD values of different mAs and different IMR. Radiation dose [volume CT dose index (CTDI vol ) and dose length product (DLP)] was positively correlated with tube current. In L1 with low BMD, different mAs in FBP showed P<0.05, indicating statistically significant BMD in ESP. In other iterative algorithms, different mAs under same iterative algorithms showed P>0.05, indicating no difference in BMD. And P>0.05 was observed among BMD of spine phantom in L1, L2 and L3 under same mAs joined with varied iterative reconstruction. The BMD in L1 varied greatly during FBP reconstruction, and less variation was observed in reconstruction of IMR [1] and IMR [2]. The BMD of L2 changed more during FBP reconstruction, where less was observed in IMR [2]. The BMD of L3 varied greatly during FBP reconstruction, and was less varied in all levels of iDose 4 and reconstruction of IMR [2]. In addition, along with continuous mAs incensement, the CNRs in various algorithms continued to increase. Among them, CNR with the FBP algorithm is the lowest, and CNR of the IMR [3] algorithm is the highest. Repeated measurements of BMD with QCT in the ESP multicenter showed that BMD changes in L1-L3 are the least varied at IMR [2] algorithm. It is recommended to scan at 120 kV with 20 mAs combined with IMR [2] algorithm. In this way, the BMD of spine by QCT could be accurately measured, while radiation dosage significantly reduced and imaging quality improved at the same time.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity.

PubMed

Vilayphiou, Nicolas; Boutroy, Stephanie; Sornay-Rendu, Elisabeth; Van Rietbergen, Bert; Chapurlat, Roland

2016-02-01

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. Copyright © 2015 Elsevier Inc. All rights reserved.

Zero-point energy conservation in classical trajectory simulations: Application to H2CO

NASA Astrophysics Data System (ADS)

Lee, Kin Long Kelvin; Quinn, Mitchell S.; Kolmann, Stephen J.; Kable, Scott H.; Jordan, Meredith J. T.

2018-05-01

A new approach for preventing zero-point energy (ZPE) violation in quasi-classical trajectory (QCT) simulations is presented and applied to H2CO "roaming" reactions. Zero-point energy may be problematic in roaming reactions because they occur at or near bond dissociation thresholds and these channels may be incorrectly open or closed depending on if, or how, ZPE has been treated. Here we run QCT simulations on a "ZPE-corrected" potential energy surface defined as the sum of the molecular potential energy surface (PES) and the global harmonic ZPE surface. Five different harmonic ZPE estimates are examined with four, on average, giving values within 4 kJ/mol—chemical accuracy—for H2CO. The local harmonic ZPE, at arbitrary molecular configurations, is subsequently defined in terms of "projected" Cartesian coordinates and a global ZPE "surface" is constructed using Shepard interpolation. This, combined with a second-order modified Shepard interpolated PES, V, allows us to construct a proof-of-concept ZPE-corrected PES for H2CO, Veff, at no additional computational cost to the PES itself. Both V and Veff are used to model product state distributions from the H + HCO → H2 + CO abstraction reaction, which are shown to reproduce the literature roaming product state distributions. Our ZPE-corrected PES allows all trajectories to be analysed, whereas, in previous simulations, a significant proportion was discarded because of ZPE violation. We find ZPE has little effect on product rotational distributions, validating previous QCT simulations. Running trajectories on V, however, shifts the product kinetic energy release to higher energy than on Veff and classical simulations of kinetic energy release should therefore be viewed with caution.

Stresses and pressures at the quartz-coesite transition in shear experiments

NASA Astrophysics Data System (ADS)

Richter, B.; Stunitz, H.; Heilbronner, R.

2015-12-01

Experiments on quartz (qtz) gouge were performed in a Griggs-type deformation apparatus at displacement rates of ~1.3 x 10-5 mms-1 or ~1.3 x 10-4 mms-1, at Pc= 1.0 GPa or 1.5 GPa and T = 600°C to 800°C. The starting material is a natural hydrothermally grown single crystal that was crushed to a powder with grain size d < 100 µm. Coesite (coe) is found if the maximum principle stress (σ1) is in the coe stability field. In general Pc and the mean stress (Pm) of these samples are below the quartz-coesite phase transition (QCT). Coe is not found if σ1 is below the QCT. At T = 600 °C, σ1is always in the coe stability field. But coe is only present in the high strain experiment, indicating slow transformation kinetics. In one sample we observed that σ1crosses the QCT during the loading part and after progressive weakening crosses the QCT back into the qtz stability field. The microstructure of this sample shows the formation of coe and the reverse transformation from coe to qtz. The coe growth penetrates the sample and coe grows around and in between larger qtz clasts. At high stresses, where Pm is also above the QCT, coe often forms radiating aggregates. At lower stresses, where only σ1 lies in the stability field of coe, and at low strain the coe grains have a preferred orientation of the b-axes (sub-) parallel to σ1. With increasing strain, the rigid coe grains rotate and align with the preferred qtz fabric. For coe to be found, it is sufficient that σ1 reaches values above the transformation pressure. If σ1 drops back into the qtz stability field during an experiment, a back-reaction from coe to qtz is observed. It appears therefore that the pressure that defines the QCT is not Pc or Pm, but σ1.

Bone density and structure in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation.

PubMed

Mostoufi-Moab, Sogol; Ginsberg, Jill P; Bunin, Nancy; Zemel, Babette; Shults, Justine; Leonard, Mary B

2012-04-01

Children requiring allogeneic hematopoietic stem cell transplantation (alloHSCT) have multiple risk factors for impaired bone accrual. The impact of alloHSCT on volumetric bone mineral density (vBMD) and cortical structure has not been addressed. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained in 55 alloHSCT recipients, ages 5 to 26 years, a median of 7 (range, 3-16) years after alloHSCT. pQCT outcomes were converted to sex- and race- specific Z-scores relative to age based on reference data in >700 concurrent healthy participants. Cortical section modulus (Zp; a summary measure of cortical bone structure and strength), and muscle and fat area Z-scores were further adjusted for tibia length for age Z-scores. AlloHSCT survivors had lower height Z-scores (-1.21 ± 1.25 versus 0.23 ± 0.92; p < 0.001), versus reference participants; BMI Z-scores did not differ. AlloHSCT survivors had lower trabecular vBMD (-1.05; 95% confidence interval [CI], -1.33 to -0.78; p < 0.001), cortical Zp (-0.63; 95% CI, -0.91 to -0.35; p < 0.001), and muscle (-1.01; 95% CI, -1.30 to -0.72; p < 0.001) Z-scores and greater fat (0.82; 95% CI, 0.54-1.11; p < 0.001) Z-scores, versus reference participants. Adjustment for muscle deficits eliminated Zp deficits in alloHSCT. Total body irradiation (TBI) was associated with lower trabecular vBMD (-1.30 ± 1.40 versus -0.49 ± 0.88; p = 0.01) and muscle (-1.34 ± 1.42 versus -0.34 ± 0.87; p < 0.01) Z-scores. Growth hormone deficiency (GHD) was associated with lower Zp Z-scores (-1.64 ± 2.47 versus -0.28 ± 1.24; p = 0.05); however, muscle differences were not significant (-1.69 ± 1.84 versus -0.78 ± 1.01; p = 0.09). History of graft versus host disease was not associated with pQCT outcomes. In summary, alloHSCT was associated with significant deficits in trabecular vBMD, cortical geometry, and muscle area years after transplantation. TBI and GHD were significant risk factors for musculoskeletal deficits. Future studies are needed to determine the metabolic and fracture implications of these deficits, and to identify therapies to improve bone accrual following alloHSCT during childhood. Copyright © 2012 American Society for Bone and Mineral Research.

Overcoming the exacerbating effects of ranitidine on NSAID-induced small intestinal toxicity with quercetin: Providing a complete GI solution.

PubMed

Singh, Devendra Pratap; Borse, Swapnil P; Nivsarkar, Manish

2017-06-25

There is a need to find/discover novel leads to treat complex and/or multi-factorial-pathogenic disease(s) like Nonsteroidal anti-inflammatory drugs (NSAID)-induced gastroenteropathy or gastrointestinal (GI) toxicity as it has emerged as an important medical and socioeconomic problem. There is no approved therapeutic strategy to prevent NSAID-induced enteropathic damage and highly effective gastro-protective drugs such as ranitidine hydrochloride (RAN) exacerbate it. In this purview, the multi target drug discovery approach (MTDD), combination approach and hit to lead strategies based on the foundation of ethnopharmacology and/or reverse pharmacology holds strong potential. Hence, the primary objectives of the current study were to explore the mechanism behind the preventative/curative effects of quercetin (QCT) on RAN exacerbated diclofenac sodium (DIC)-induced enteropathic damage and to assess the effects of co-administration of QCT and RAN on DIC-induced gastropathic damage in rats. Rats were treated twice daily with QCT (35, 50 and 100 mg kg -1 PO) and/or RAN (15 mg kg -1 PO) or vehicle for a total of 10 days. In some experiments, DIC (9 mg kg -1 ) was administered orally twice daily for the final 5 days of RAN/QCT + RAN/vehicle administration. Rats in all the groups were fasted after the last dose on 9th day (free access to water). 12 h after the last dose on 10th day, rats were euthanized and their GI tracts were assessed for haemorrhagic damage, alteration in xanthine oxidase (XO) activity, lipid peroxidation, intestinal permeability and GI luminal pH alterations along with haematological and biochemical estimations. The macroscopic, haematological, biochemical and histological evidences suggested that, though, RAN prevented the DIC-induced gastric injury, it exacerbated enteropathic damage. However, QCT not only significantly attenuated the RAN-induced exacerbation of enteropathic damage caused by DIC at the doses of 50 and 100 mg kg -1 , but, this combination provided complete GI safety against the toxic effects of DIC too. The mechanisms behind the gastro-enteroprotective ability of QCT may be related to its ability to inhibit XO activity thus, preventing enhanced oxidative stress on GI tissues, prevent lipid peroxidation, IP alteration and alteration in GI luminal pH. The preventative effects of QCT on NSAID-induced gastroenteropathy were ably supported by the QCT induced prevention of GI blood loss and serum protein loss. These pharmaco-mechanistic results of QCT are aligning to combination based MTDD approach and hence we propose it as a promising lead to treat NSAID-gastroenteropahty and related complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Skeletal assessment with finite element analysis: relevance, pitfalls and interpretation.

PubMed

Campbell, Graeme Michael; Glüer, Claus-C

2017-07-01

Finite element models simulate the mechanical response of bone under load, enabling noninvasive assessment of strength. Models generated from quantitative computed tomography (QCT) incorporate the geometry and spatial distribution of bone mineral density (BMD) to simulate physiological and traumatic loads as well as orthopaedic implant behaviour. The present review discusses the current strengths and weakness of finite element models for application to skeletal biomechanics. In cadaver studies, finite element models provide better estimations of strength compared to BMD. Data from clinical studies are encouraging; however, the superiority of finite element models over BMD measures for fracture prediction has not been shown conclusively, and may be sex and site dependent. Therapeutic effects on bone strength are larger than for BMD; however, model validation has only been performed on untreated bone. High-resolution modalities and novel image processing methods may enhance the structural representation and predictive ability. Despite extensive use of finite element models to study orthopaedic implant stability, accurate simulation of the bone-implant interface and fracture progression remains a significant challenge. Skeletal finite element models provide noninvasive assessments of strength and implant stability. Improved structural representation and implant surface interaction may enable more accurate models of fragility in the future.

Bone disease in primary hyperparathyroidism

PubMed Central

Bandeira, Francisco; Cusano, Natalie E.; Silva, Barbara C.; Cassibba, Sara; Almeida, Clarissa Beatriz; Machado, Vanessa Caroline Costa; Bilezikian, John P.

2015-01-01

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT. PMID:25166047

Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis.

PubMed

Gao, Mei; Wang, Hui; Zhu, LiJuan

2016-01-01

Vulvovaginal candidiasis (VVC) is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ). Quercetin (QCT) is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm. 17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm. We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i) be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii) inhibit fungal adherence, cell surface hydrophobicity (CSH), flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii) down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv) the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ. Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm. © 2016 The Author(s) Published by S. Karger AG, Basel.

In vivo testing of a biodegradable woven fabric made of bioactive glass fibers and PLGA80--a pilot study in the rabbit.

PubMed

Alm, Jessica J; Frantzén, Janek P A; Moritz, Niko; Lankinen, Petteri; Tukiainen, Mikko; Kellomäki, Minna; Aro, Hannu T

2010-05-01

The purpose of this study was to perform an intra-animal comparison of biodegradable woven fabrics made of bioactive glass (BG) fibers and poly(L-lactide-co-glycolide) 80/20 copolymer (PLGA(80)) fibers or PLGA(80) fibers alone, in surgical stabilization of bone graft. The BG fibers (BG 1-98) were aimed to enhance bone growth at site of bone grafting, whereas the PLGA component was intended to provide structural strength and flexibility to the fabric. Bone formation was analyzed qualitatively by histology and quantitatively by peripheral quantitative computed tomography (pQCT) at 12 weeks. The surgical handling properties of the control PLGA(80) fabric were more favorable. Both fabrics were integrated with the cortical bone surfaces, but BG fibers showed almost complete resorption. There were no signs of adverse local tissue reactions. As a proof of material integration and induced new bone formation, there was a significant increase in bone volume of the operated femurs compared with the contralateral intact bone (25% with BG/PLGA(80) fabric, p < 0.001 and 28% with the control PLGA(80) fabric, p = 0.006). This study failed to demonstrate the previously seen positive effect of BG 1-98 on osteogenesis, probably due to the changed resorption properties of BG in the form of fibers. Therefore, the feasibility and safety of BG as fibers needs to be reevaluated before use in clinical applications. (c) 2010 Wiley Periodicals, Inc.

Structural analysis of cortical porosity applied to HR-pQCT data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tjong, Willy, E-mail: wwtjong@gmail.com; Nirody, Jasmine, E-mail: jnirody@berkeley.edu; Burghardt, Andrew J., E-mail: andrew.burghardt@ucsf.edu

2014-01-15

Purpose: The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualizedin vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology. Methods: Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82μm) and also using μCT at amore » voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%). Results: Correlations toμCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r{sup 2} = 0.82, p < 0.001, 82: r{sup 2} = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r{sup 2} = 0.72, p < 0.01) Data at both HR-pQCT voxel sizes were strongly predictive of the μCT values for N.Slabs (41: r{sup 2} = 0.93, p < 0.001; 82: r{sup 2} = 0.84, p < 0.001), N.Tubes (41: r{sup 2} = 0.94, p < 0.001; 82: r{sup 2} = 0.84, p < 0.001), and N.Junctions (41: r{sup 2} = 0.93, p < 0.001; 82: r{sup 2} = 0.78, p < 0.001), though proportional bias was evident in these correlations. Weak correlations were seen for iSlab.Vol/iTube.Vol at both voxel sizes (41: r{sup 2} = 0.52, p < 0.01; 82: r{sup 2} = 0.39, p < 0.05). Slab.Vol was significantly correlated to μCT data at 41 μm (r{sup 2} = 0.60, p < 0.01) but not at 82 μm, while Tube.Vol was significantly correlated at both voxel sizes (41: r{sup 2} = 0.79, p < 0.001; 82: r{sup 2} = 0.68, p < 0.01). In vivo precision error for these parameters ranged from 2.31 to 9.68 RMSCV%. Conclusions: Strong correlations betweenμCT- and HR-pQCT-derived measurements were found, particularly in HR-pQCT images obtained at 41 μm. These data are in agreement with our previous study investigating the effect of voxel size on standard HR-pQCT metrics of trabecular and cortical microstructure, and extend our previous findings to include topological descriptors of the cortical pore network.« less

In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy.

PubMed

Golomb, Meredith R; McDonald, Brenna C; Warden, Stuart J; Yonkman, Janell; Saykin, Andrew J; Shirley, Bridget; Huber, Meghan; Rabin, Bryan; Abdelbaky, Moustafa; Nwosu, Michelle E; Barkat-Masih, Monica; Burdea, Grigore C

2010-01-01

Golomb MR, McDonald BC, Warden SJ, Yonkman J, Saykin AJ, Shirley B, Huber M, Rabin B, AbdelBaky M, Nwosu ME, Barkat-Masih M, Burdea GC. In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy. To investigate whether in-home remotely monitored virtual reality videogame-based telerehabilitation in adolescents with hemiplegic cerebral palsy can improve hand function and forearm bone health, and demonstrate alterations in motor circuitry activation. A 3-month proof-of-concept pilot study. Virtual reality videogame-based rehabilitation systems were installed in the homes of 3 participants and networked via secure Internet connections to the collaborating engineering school and children's hospital. Adolescents (N=3) with severe hemiplegic cerebral palsy. Participants were asked to exercise the plegic hand 30 minutes a day, 5 days a week using a sensor glove fitted to the plegic hand and attached to a remotely monitored videogame console installed in their home. Games were custom developed, focused on finger movement, and included a screen avatar of the hand. Standardized occupational therapy assessments, remote assessment of finger range of motion (ROM) based on sensor glove readings, assessment of plegic forearm bone health with dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), and functional magnetic resonance imaging (fMRI) of hand grip task. All 3 adolescents showed improved function of the plegic hand on occupational therapy testing, including increased ability to lift objects, and improved finger ROM based on remote measurements. The 2 adolescents who were most compliant showed improvements in radial bone mineral content and area in the plegic arm. For all 3 adolescents, fMRI during grip task contrasting the plegic and nonplegic hand showed expanded spatial extent of activation at posttreatment relative to baseline in brain motor circuitry (eg, primary motor cortex and cerebellum). Use of remotely monitored virtual reality videogame telerehabilitation appears to produce improved hand function and forearm bone health (as measured by DXA and pQCT) in adolescents with chronic disability who practice regularly. Improved hand function appears to be reflected in functional brain changes. Copyright (c) 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study.

PubMed

Almirol, Ellen A; Chi, Lisa Y; Khurana, Bharti; Hurwitz, Shelley; Bluman, Eric M; Chiodo, Christopher; Matzkin, Elizabeth; Baima, Jennifer; LeBoff, Meryl S

2016-09-01

In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine the effects of TPTD treatment on stress fracture healing in premenopausal women.

Increased Cortical Porosity in Type-2 Diabetic Postmenopausal Women with Fragility Fractures

PubMed Central

Patsch, Janina M.; Burghardt, Andrew J.; Yap, Samuel P.; Baum, Thomas; Schwartz, Ann V.; Joseph, Gabby B.; Link, Thomas M.

2012-01-01

The primary goal of this study was to assess peripheral bone microarchitecture and strength in diabetic postmenopausal women with fragility fractures (DMFx) and to compare them with diabetic women without fracture (DM). Secondary goals were to assess differences in non-diabetic women with (Fx) and without fragility fractures (Co) and in women with (DM) and without diabetes (Co). Eighty women (mean age 61.3±5.7 yrs) were recruited into these groups (n=20 per group). Participants underwent DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density, cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro-finite element analysis (μFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p=0.009; +95.4%, p=0.020), relative porosity (+58.1%; p=0.005; +87.9%, p=0.011) and endocortical bone surface (+10.9%, p=0.031; +11.5%, 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p=0.000) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p=0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius; +36.8%, p=0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p=0.031; −6.8%, p=0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing non-diabetic Fx and Co, we only found a non-significant trend with increase in pore volume (+38.9%, p=0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. PMID:22991256

Dairy food intake, peripheral bone structure, and muscle mass in elderly ambulatory women.

PubMed

Radavelli-Bagatini, Simone; Zhu, Kun; Lewis, Joshua R; Prince, Richard L

2014-07-01

Previous studies suggest that dairy intake may be associated with reduced bone and muscle loss with aging, but there are limited data in the very old. We evaluated the association between intake of dairy foods and peripheral bone structure and muscle mass in 564 elderly women aged 80 to 92 (mean 84.7) years, who were participants of the Calcium Intake Fracture Outcome Study/CAIFOS Aged Extension Study (CAIFOS/CARES) cohort and attended the 10-year follow-up. Assessments included dairy consumption (milk, yogurt, and cheese) by a validated food frequency questionnaire, 15% tibia bone mass, area and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), and appendicular bone and skeletal muscle mass by dual-energy X-ray absorptiometry (DXA). Women were categorized according to tertiles of dairy intake: first tertile (≤ 1.5 servings/d), second tertile (1.5 to 2.2 servings/d) and third tertile (≥ 2.2 servings/d). Controlling for confounding factors, pQCT assessment at the 15% tibia showed that compared with those in the first tertile of dairy intake, women in the third tertile had 5.7% greater total bone mass (p = 0.005), principally because of an increase in cortical and subcortical bone mass (5.9%, p = 0.050), resulting in a 6.2% increase in total vBMD (p = 0.013). Trabecular but not cortical and subcortical vBMD was also higher (7.8%, p = 0.044). DXA assessment showed that women in the third tertile of dairy intake had greater appendicular bone mass (7.1%, p = 0.007) and skeletal muscle mass (3.3%, p = 0.014) compared with tertile 1. The associations with bone measures were dependent on dairy protein and calcium intakes, whereas the association with appendicular muscle mass was not totally dependent on dairy protein intake. Our results suggest a positive association of dairy intake with appendicular bone mineralization and muscle mass in elderly women. Because many fractures in this age group are of the appendicular skeleton often associated with falls, dairy intake may be a modifiable lifestyle factor contributing to healthy aging. © 2014 American Society for Bone and Mineral Research.

Duck gait: Relationship to hip angle, bone ash, bone density, and morphology.

PubMed

Robison, Cara I; Rice, Meredith; Makagon, Maja M; Karcher, Darrin M

2015-05-01

The rapid growth meat birds, including ducks, undergo requires skeletal integrity; however, fast growth may not be conducive to adequate bone structure. A relationship likely exists between skeletal changes and duck mobility. Reduced mobility in meat ducks may have impacts on welfare and production. This study examined the relationships among gait score, bone parameters, and hip angle. Commercial Pekin ducks, ages 14 d (n = 100), 21 d (n = 100), and 32 d (n = 100) were weighed and gait scored with a 3-point gait score system by an observer as they walked over a Tekscan gait analysis system. Gait was scored as GS0, GS1, or GS2 with a score of GS0 defined as good walking ability and a score of GS2 as poorest walking ability. Ducks were humanely euthanized, full body scanned using quantitative computed tomography (QCT), and the right femur and tibia were extracted. Leg bones were cleaned, measured, fat extracted, and ashed. QCT scans were rendered to create computerized 3D models where pelvic hip angles and bone density were measured. Statistical analysis was conducted using PROC MIXED with age and gait score in the model. Body weight increased with age, but within an age, body weight decreased as walking ability became worse (P < 0.01). As expected, linear increases in tibia and femur bone width and length were observed as the ducks aged (P < 0.01). Right and left hip angle increased with duck age (P < 0.01). Additionally, ducks with a GS2 had wider hip angles opposed to ducks with a GS0 (P < 0.01). Bone density increased linearly with both age and gait score (P < 0.05). Femur ash content was lowest in 32-day-old ducks and ducks with GS1 and GS2 (P < 0.0001). Tibia ash content increased with age, but decreased as gait score increased (P < 0.001). The observation that right hip angle changed with gait scores merits further investigation into the relationship between duck mobility and skeletal changes during growth. © 2015 Poultry Science Association Inc.

Dairy product intake and bone properties in 70-year-old men and women.

PubMed

Hallkvist, Olle M; Johansson, Jonas; Nordström, Anna; Nordström, Peter; Hult, Andreas

2018-01-29

In the present population-based study including 70-year-old men and women, total dairy product intake was associated with a weak positive association with tibia trabecular and cortical cross-sectional areas. Milk consumption has recently been suggested to increase fracture risk. Therefore, we aimed to investigate associations between dairy product consumption and peripheral bone properties. Furthermore, we explored whether consumption of milk and fermented dairy products affected bone properties differently. The Healthy Aging Initiative is a population-based, cross-sectional study investigating the health of 70-year-old men and women. Out of the 2904 individuals who met the inclusion criteria, data on self-reported daily dairy product consumption (dl/day), peripheral quantitative computed tomography (pQCT) examinations at the 4 and 66% scan sites of the tibia and radius, and dual-energy X-ray absorptiometry (DXA) scans were collected from 2040 participants. Associations between dairy product consumption and bone properties were examined using multiple linear regression models adjusted for sex, muscle area, meal size, dietary protein proportion, current smoking status, and objectively measured physical activity. Total dairy product intake was associated with larger trabecular (2.296 (95% CI, 0.552-4.039) mm 2 , per dl/day increase, p = 0.01) and cortical cross-sectional areas (CSAs) in the tibia (1.757 (95% CI, 0.683-2.830 mm 2 , p = 0.001) as measured by pQCT and higher areal bone mineral density (aBMD) of the radius (3.231 (95% CI, 0.764-5.698) mg/cm 2 , p = 0.01) as measured by DXA. No other measurement in the tibia, radius, femoral neck, or lower spine was associated significantly with dairy product intake. Bone properties did not differ according to the type of dairy product consumed. No evidence of a negative association between dairy product consumption and bone health was found. Furthermore, total dairy product consumption was associated with increased CSAs in the tibia, regardless of dairy product type. Collectively, our findings indicate the existence of a weak but significant positive association between dairy product consumption bone properties in older adults.

Accelerated bone loss in older men: Effects on bone microarchitecture and strength.

PubMed

Cauley, J A; Burghardt, A J; Harrison, S L; Cawthon, P M; Schwartz, A V; Connor, E Barrett; Ensrud, Kristine E; Langsetmo, Lisa; Majumdar, S; Orwoll, E

2018-05-11

Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high resolution peripheral quantitative computed tomography (HR-pQCT) scans (SCANCO, Inc., Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal (a) bone mineral density (BMD) change from the Year 7 to Year 14 exam in 3 categories: "accelerated" >10% loss at either the total hip or femoral neck, (N = 299, 18.4%); "expected" loss, <10%, (N = 1061, 65.2%) and "maintained" BMD, ≥0%, (N = 268, 16.5%). The ABL cutoff was a safety alert established for MrOS. We used regression models to calculate adjusted mean HR-pQCT parameters in men with ABL, expected loss or maintained BMD. Men who experienced ABL were older and had a lower body mass index and aBMD and experienced greater weight loss compared to other men. Total volumetric BMD and trabecular and cortical volumetric BMD were lower in men with ABL compared to the expected or maintained group. Men with ABL had significantly lower trabecular bone volume fraction (BV/TV), fewer trabeculae and greater trabecular separation at both the distal radius and tibia than men with expected loss or who maintained aBMD, all p trend <0.001. Men with ABL had lower cortical thickness and lower estimated bone strength but there was no difference in cortical porosity except at the tibia diaphyseal site In summary, men with ABL have lower estimated bone strength, poorer trabecular microarchitecture and thinner cortices than men without ABL but have similar cortical porosity. These impairments may lead to an increased risk of fracture. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Bone strength and muscle properties in postmenopausal women with and without a recent distal radius fracture.

PubMed

Crockett, K; Arnold, C M; Farthing, J P; Chilibeck, P D; Johnston, J D; Bath, B; Baxter-Jones, A D G; Kontulainen, S A

2015-10-01

Distal radius (wrist) fracture (DRF) in women over age 50 years is an early sign of bone fragility. Women with a recent DRF compared to women without DRF demonstrated lower bone strength, muscle density, and strength, but no difference in dual-energy x-ray absorptiometry (DXA) measures, suggesting DXA alone may not be a sufficient predictor for DRF risk. The objective of this study was to investigate differences in bone and muscle properties between women with and without a recent DRF. One hundred sixty-six postmenopausal women (50-78 years) were recruited. Participants were excluded if they had taken bone-altering medications in the past 6 months or had medical conditions that severely affected daily living or the upper extremity. Seventy-seven age-matched women with a fracture in the past 6-24 months (Fx, n = 32) and without fracture (NFx, n = 45) were measured for bone and muscle properties using the nondominant (NFx) or non-fractured limb (Fx). Peripheral quantitative computed tomography (pQCT) was used to estimate bone strength in compression (BSIc) at the distal radius and tibia, bone strength in torsion (SSIp) at the shaft sites, muscle density, and area at the forearm and lower leg. Areal bone mineral density at the ultradistal forearm, spine, and femoral neck was measured by DXA. Grip strength and the 30-s chair stand test were used as estimates of upper and lower extremity muscle strength. Limb-specific between-group differences were compared using multivariate analysis of variance (MANOVA). There was a significant group difference (p < 0.05) for the forearm and lower leg, with the Fx group demonstrating 16 and 19% lower BSIc, 3 and 6% lower muscle density, and 20 and 21% lower muscle strength at the upper and lower extremities, respectively. There were no differences between groups for DXA measures. Women with recent DRF had lower pQCT-derived estimated bone strength at the distal radius and tibia and lower muscle density and strength at both extremities.

Comparison between phenomenological and ab-initio reaction and relaxation models in DSMC

NASA Astrophysics Data System (ADS)

Sebastião, Israel B.; Kulakhmetov, Marat; Alexeenko, Alina

2016-11-01

New state-specific vibrational-translational energy exchange and dissociation models, based on ab-initio data, are implemented in direct simulation Monte Carlo (DSMC) method and compared to the established Larsen-Borgnakke (LB) and total collision energy (TCE) phenomenological models. For consistency, both the LB and TCE models are calibrated with QCT-calculated O2+O data. The model comparison test cases include 0-D thermochemical relaxation under adiabatic conditions and 1-D normal shockwave calculations. The results show that both the ME-QCT-VT and LB models can reproduce vibrational relaxation accurately but the TCE model is unable to reproduce nonequilibrium rates even when it is calibrated to accurate equilibrium rates. The new reaction model does capture QCT-calculated nonequilibrium rates. For all investigated cases, we discuss the prediction differences based on the new model features.

The QUALYOR (QUalité Osseuse LYon Orléans) study: a new cohort for non invasive evaluation of bone quality in postmenopausal osteoporosis. Rationale and study design.

PubMed

Chapurlat, Roland; Pialat, Jean-Baptiste; Merle, Blandine; Confavreux, Elisabeth; Duvert, Florence; Fontanges, Elisabeth; Khacef, Farida; Peres, Sylvie Loiseau; Schott, Anne-Marie; Lespessailles, Eric

2017-12-27

The diagnostic performance of densitometry is inadequate. New techniques of non-invasive evaluation of bone quality may improve fracture risk prediction. Testing the value of these techniques is the goal of the QUALYOR cohort. The bone mineral density (BMD) of postmenopausal women who sustain osteoporotic fracture is generally above the World Health Organization definition for osteoporosis. Therefore, new approaches to improve the detection of women at high risk for fracture are warranted. We have designed and recruited a new cohort to assess the predictive value of several techniques to assess bone quality, including high-resolution peripheral quantitative computerized tomography (HRpQCT), hip QCT, calcaneus texture analysis, and biochemical markers. We have enrolled 1575 postmenopausal women, aged at least 50, with an areal BMD femoral neck or lumbar spine T-score between - 1.0 and - 3.0. Clinical risk factors for fracture have been collected along with serum and blood samples. We describe the design of the QUALYOR study. Among these 1575 women, 80% were aged at least 60. The mean femoral neck T-score was - 1.6 and the mean lumbar spine T-score was -1.2. This cohort is currently being followed up. QUALYOR will provide important information on the relationship between bone quality variables and fracture risk in women with moderately decreased BMD.

Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in men.

PubMed

Vilayphiou, Nicolas; Boutroy, Stephanie; Szulc, Pawel; van Rietbergen, Bert; Munoz, Francoise; Delmas, Pierre D; Chapurlat, Roland

2011-05-01

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case-control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)-pQCT, and finite element (µFE) analysis was based on HR-pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from -6% to 15%. µFE-derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE-derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27-2.12] (2.21 [1.60-3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00-1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16-2.09] (2.21 [1.59-3.07]), and with PC2, with OR = 1.55 [1.17-2.06] (1.45 [1.06-1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties. Copyright © 2011 American Society for Bone and Mineral Research.

The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

NASA Technical Reports Server (NTRS)

Pennline, James; Mulugeta, Lealem

2013-01-01

Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise prescriptions on preserving bone. More specifically, the model will accept loading history due to muscle and joint force on bone and produce quantified remodeling within the bone region under influence of the applied stress. Furthermore, because they tend to respond differently, the bone remodeling model includes both trabecular bone and cortical bone.

Comparison of cross sections from the quasi-classical trajectory method and the j(z)-conserving centrifugal sudden approximation with accurate quantum results for an atom-rigid nonlinear polyatomic collision

NASA Technical Reports Server (NTRS)

Schwenke, David W.

1993-01-01

We report the results of a series of calculations of state-to-state integral cross sections for collisions between O and nonvibrating H2O in the gas phase on a model nonreactive potential energy surface. The dynamical methods used include converged quantum mechanical scattering calculations, the j(z) conserving centrifugal sudden (j(z)-CCS) approximation, and quasi-classical trajectory (QCT) calculations. We consider three total energies 0.001, 0.002, and 0.005 E(h) and the nine initial states with rotational angular momentum less than or equal to 2 (h/2 pi). The j(z)-CCS approximation gives good results, while the QCT method can be quite unreliable for transitions to specific rotational sublevels. However, the QCT cross sections summed over final sublevels and averaged over initial sublevels are in better agreement with the quantum results.

Bisphosphonate ISS Flight Experiment

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey; Shapiro, Jay; Lang, Thomas; Shackleford, Linda; Smith, Scott M.; Evans, Harlan; Spector, Elizabeth; Ploutz-Snyder, Robert;

Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects.

PubMed

Choi, Jiwoong; Hoffman, Eric A; Lin, Ching-Long; Milhem, Mohammed M; Tessier, Jean; Newell, John D

2017-01-01

Extra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells) through interactions with host cells. We explored this with serial inspiratory computed tomography (CT) and image matching to assess regional changes in lung expansion. We retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05. Lung regions of metastatic sarcoma patients (but not the normal control group) demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05). There was also evidence of increased lung "tissue" volume (non-air components) in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. "Tissue" volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions. This new quantitative CT (QCT) method for linking serial acquired inspiratory CT images may provide a diagnostic and prognostic means to objectively characterize regional responses in the lung following oncological treatment and monitoring for lung metastases.

Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study.

PubMed

Edwards, Mark H; Ward, Kate A; Ntani, Georgia; Parsons, Camille; Thompson, Jennifer; Sayer, Avan A; Dennison, Elaine M; Cooper, Cyrus

2015-12-01

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72-81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p<0.01), cortical thickness (p<0.05) and trabecular number (p<0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p<0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations. Copyright © 2015 Elsevier Inc. All rights reserved.

Gymnastics participation is associated with skeletal benefits in the distal forearm: a 6-month study using peripheral Quantitative Computed Tomography.

PubMed

Burt, L A; Ducher, G; Naughton, G A; Courteix, D; Greene, D A

2013-12-01

Musculoskeletal development of the upper limbs during exposure to weight-bearing loading is under-researched during early pubescent growth. The purpose was to assess the changes in upper body musculoskeletal strength in young girls following 6 months of non-elite gymnastics participation. Eighty-four girls, 6-12 years were divided into groups based on gymnastics participation: high-training (HGYM, 6-16 hr/wk), low-training (LGYM, 1-5 hr/wk), and non-gymnasts (NONGYM). Volumetric BMD, bone geometry, estimated bone strength and muscle size were assessed at the non-dominant forearm (4% and 66% radius and ulna) with pQCT. DXA assessed aBMD and body composition. Tests for explosive power, muscle strength, and endurance were also performed. Interaction effects were observed in all variables at the 4% radius. At the 66% ulna, HGYM and LGYM had greater bone mass, size and bone strength than NONGYM, furthermore a dose-response relationship was observed at this location. Body composition was better for HGYM than LGYM and NONGYM, however muscle function was better for HGYM and LGYM than NONGYM. The greatest changes were obtained with more than one gymnastics class per week. Separating gymnastics participation-related changes from those associated with normal growth and development remains difficult, particularly at the 4% radius.

Epistasis between QTLs for bone density variation in Copenhagen × dark agouti F2 rats

PubMed Central

Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

2010-01-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation. PMID:19153792

Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats.

PubMed

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2009-03-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.

A time course of bone response to jump exercise in C57BL/6J mice.

PubMed

Umemura, Yoshihisa; Baylink, David J; Wergedal, Jon E; Mohan, Subburaman; Srivastava, Apurva K

2002-01-01

Exercise, by way of mechanical loading, provides a physiological stimulus to which bone tissue adapts by increased bone formation. The mechanical stimulus due to physical activity depends on both the magnitude and the duration of the exercise. Earlier studies have demonstrated that jump training for 4 weeks produces a significant bone formation response in C57BL/6J mice. An early time point with significant increase in bone formation response would be helpful in: (1) designing genetic quantitative trait loci (QTL) studies to investigate genes regulating the bone adaptive response to mechanical stimulus; and (2) mechanistic studies to investigate early stimulus to bone tissue. Consequently, we investigated the bone structural response after 2, 3, and 4 weeks of exercise with a loading cycle of ten jumps a day. We used biochemical markers and peripheral quantitative computed tomography (pQCT) of excised femur to measure bone density, bone mineral content (BMC), and area. Four-week-old mice were separated into control ( n = 6) and jump groups ( n = 6), and the latter groups of mice were subjected to jump exercise of 2-week, 3-week, and 4-week duration. Data (pQCT) from a mid-diaphyseal slice were used to compare bone formation parameters between exercise and control groups, and between different time points. There was no statistically significant change in bone response after 2 weeks of jump exercise as compared with the age-matched controls. After 3 weeks of jump exercise, the periosteal circumference, which is the most efficient means of measuring adaptation to exercise, was increased by 3% ( P < 0.05), and total and cortical area were increased by 6% ( P < 0.05) and 11% ( P < 0.01), respectively. Total bone mineral density (BMD) increased by 11% ( P < 0.01). The biggest changes were observed in cortical and total BMC, with the increase in total BMC being 12% ( P < 0.01). Interestingly, the increase in BMC was observed throughout the length of the femur and was not confined to the mid-diaphysis. Consistent with earlier studies, mid-femur bone mass and area remained significantly elevated in the 4-week exercise group when compared with the control group of mice. The levels of the biochemical markers osteocalcin, skeletal alkaline phosphatase, and C-telopeptide were not significantly different between the exercise and control groups, indicating the absence of any systemic response due to the exercise. We conclude that a shorter exercise regimen, of 3 weeks, induced a bone response that was greater than or equal to that of 4 weeks of jump exercise reported earlier.

The Cl + O3 reaction: a detailed QCT simulation of molecular beam experiments.

PubMed

Menéndez, M; Castillo, J F; Martínez-Haya, B; Aoiz, F J

2015-10-14

We have studied in detail the dynamics of the Cl + O3 reaction in the 1-56 kcal mol(-1) collision energy range using quasi-classical trajectory (QCT) calculations on a recent potential energy surface (PES) [J. F. Castillo et al., Phys. Chem. Chem. Phys., 2011, 13, 8537]. The main goal of this work has been to assess the accuracy of the PES and the reliability of the QCT method by comparison with the existing crossed molecular beam results [J. Zhang and Y. T. Lee J. Phys. Chem. A, 1997, 101, 6485]. For this purpose, we have developed a methodology that allows us to determine the experimental observables in crossed molecular beam experiments (integral and differential cross sections, recoil velocity distributions, scattering angle-recoil velocity polar maps, etc.) as continuous functions of the collision energy. Using these distributions, raw experimental data in the laboratory frame (angular distributions and time-of-flight spectra) have been simulated from first principles with the sole information on the instrumental parameters and taking into account the energy spread. A general good agreement with the experimental data has been found, thereby demonstrating the adequacy of the QCT method and the quality of the PES to describe the dynamics of this reaction at the level of resolution of the existing crossed beam experiments. Some features which are apparent in the differential cross sections have also been analysed in terms of the dynamics of the reaction and its evolution with the collision energy.

Bioimpedance profiling of the limbs: Update

NASA Astrophysics Data System (ADS)

Ward, L. C.; Essex, T.; Bartlett, M.; Kilbreath, S.; Brookes, D.

2010-04-01

Bioelectrical impedance spectroscopy (BIS) is now commonly used to assess breast cancer-related lymphoedema. Typically, the ratio of impedances of the two arms, determined at zero frequency (Z0), is used as a quantitative index of the presence of excess lymph. Measurement uses skin electrodes spanning the whole limb. However, lymphoedema may be highly localised and may involve changes other than simple fluid accumulation, e.g. increased fat and fibrosis, that also give rise to changes in impedance-related parameters such as capacitance. We have previously reported (13th ICEBI, Graz, 2007) a prototype mobile electrode probe that replaces the distal sense electrode which, when moved proximally along the arm, provides an impedance profile. We report here the further development of this technology to incorporate real-time measurement of impedance integrated with a digital measuring wheel. This allows exact synchronisation of impedance with position on the arm. A commercial BIS instrument (ImpediMed SFB7) was modified to collect impedance (R and Xc) data every msec and the mean impedance computed for each 10-mm slice. The apparent resistivity values for arm tissue were used to calculate slice volumes. These computed volumes were compared to equivalent slice volumes from perometry and DXA. The system is being further validated by correlating slice impedance parameters with lean tissue volume determined by pQCT (StraTec XCT 3000), for multiple positions along the arm. Ultimately, it is hoped that such measurements will not only allow localised tissue volume measurement but will also provide information of tissue composition in conditions such as lymphoedema.

Association of QCT Bone Mineral Density and Bone Structure With Vertebral Fractures in Patients With Multiple Myeloma.

PubMed

Borggrefe, Jan; Giravent, Sarah; Thomsen, Felix; Peña, Jaime; Campbell, Graeme; Wulff, Asmus; Günther, Andreas; Heller, Martin; Glüer, Claus C

2015-07-01

Computed tomography (CT) is used for staging osteolytic lesions and detecting fractures in patients with multiple myeloma (MM). In the OsteoLysis of Metastases and Plasmacell-infiltration Computed Tomography 2 study (OLyMP-CT) study we investigated whether patients with and without vertebral fractures show differences in bone mineral density (BMD) or microstructure that could be used to identify patients at risk for fracture. We evaluated whole-body CT scans in a group of 104 MM patients without visible osteolytic lesions using an underlying lightweight calibration phantom (Image Analysis Inc., Columbia, KY, USA). QCT software (StructuralInsight) was used for the assessment of BMD and bone structure of the T11 or T12 vertebral body. Age-adjusted standardized odds ratios (sORs) per SD change were derived from logistic regression analyses, and areas under the receiver operating characteristics (ROC) curve (AUCs) analyses were calculated. Forty-six of the 104 patients had prevalent vertebral fractures (24/60 men, 22/44 women). Patients with fractures were not significantly older than patients without fractures (mean ± SD, 64 ± 9.2 versus 62 ± 12.3 years; p = 0.4). Trabecular BMD in patients with fractures versus without fractures was 169 ± 41 versus 192 ± 51 mg/cc (AUC = 0.62 ± 0.06, sOR = 1.6 [1.1 to 2.5], p = 0.02). Microstructural variables achieved optimal discriminatory power at bone thresholds of 150 mg/cc. Best fracture discrimination for single microstructural variables was observed for trabecular separation (Tb.Sp) (AUC = 0.72 ± 0.05, sOR = 2.4 (1.5 to 3.9), p < 0.0001). In multivariate models AUCs improved to 0.77 ± 0.05 for BMD and Tb.Sp, and 0.79 ± 0.05 for Tb.Sp and trabecular thickness (Tb.Th). Compared to BMD values, these improvements of AUC values were statistically significant (p < 0.0001). In MM patients, QCT-based analyses of bone structure derived from routine CT scans permit discrimination of patients with and without vertebral fractures. Rarefaction of the trabecular network due to plasma cell infiltration and osteoporosis can be measured. Deterioration of microstructural measures appear to be of value for vertebral fracture risk assessment and may indicate early stages of osteolytic processes not yet visible. © 2014 American Society for Bone and Mineral Research.

Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures.

PubMed

Patsch, Janina M; Li, Xiaojuan; Baum, Thomas; Yap, Samuel P; Karampinos, Dimitrios C; Schwartz, Ann V; Link, Thomas M

2013-08-01

The goal of this magnetic resonance (MR) imaging study was to quantify vertebral bone marrow fat content and composition in diabetic and nondiabetic postmenopausal women with fragility fractures and to compare them with nonfracture controls with and without type 2 diabetes mellitus. Sixty-nine postmenopausal women (mean age 63 ± 5 years) were recruited. Thirty-six patients (47.8%) had spinal and/or peripheral fragility fractures. Seventeen fracture patients were diabetic. Thirty-three women (52.2%) were nonfracture controls. Sixteen women were diabetic nonfracture controls. To quantify vertebral bone marrow fat content and composition, patients underwent MR spectroscopy (MRS) of the lumbar spine at 3 Tesla. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine (LS) and quantitative computed tomography (QCT) of the LS. To evaluate associations of vertebral marrow fat content and composition with spinal and/or peripheral fragility fractures and diabetes, we used linear regression models adjusted for age, race, and spine volumetric bone mineral density (vBMD) by QCT. At the LS, nondiabetic and diabetic fracture patients had lower vBMD than controls and diabetics without fractures (p = 0.018; p = 0.005). However, areal bone mineral density (aBMD) by DXA did not differ between fracture and nonfracture patients. After adjustment for age, race, and spinal vBMD, the prevalence of fragility fractures was associated with -1.7% lower unsaturation levels (confidence interval [CI] -2.8% to -0.5%, p = 0.005) and +2.9% higher saturation levels (CI 0.5% to 5.3%, p = 0.017). Diabetes was associated with -1.3% (CI -2.3% to -0.2%, p = 0.018) lower unsaturation and +3.3% (CI 1.1% to 5.4%, p = 0.004) higher saturation levels. Diabetics with fractures had the lowest marrow unsaturation and highest saturation. There were no associations of marrow fat content with diabetes or fracture. Our results suggest that altered bone marrow fat composition is linked with fragility fractures and diabetes. MRS of spinal bone marrow fat may therefore serve as a novel tool for BMD-independent fracture risk assessment. Copyright © 2013 American Society for Bone and Mineral Research.

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) research group.

PubMed

Katzman, Wendy B; Miller-Martinez, Dana; Marshall, Lynn M; Lane, Nancy E; Kado, Deborah M

2014-01-16

The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women. To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m2. Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 - 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 - 38.4). These results suggest that differences in body composition may potentially influence kyphosis.

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group

PubMed Central

2014-01-01

Background The prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women. Methods To specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m2. Results Among men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 – 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 – 38.4). Conclusions These results suggest that differences in body composition may potentially influence kyphosis. PMID:24428860

Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

PubMed

Hetherington-Rauth, Megan; Bea, Jennifer W; Blew, Robert M; Funk, Janet L; Hingle, Melanie D; Lee, Vinson R; Roe, Denise J; Wheeler, Mark D; Lohman, Timothy G; Going, Scott B

2018-05-22

With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. Lean mass was a significant positive contributor to all bone outcomes (p < 0.05) with the exception of vBMD at diaphyseal sites. Fat mass was a significant contributor to bone strength at weight bearing sites, but did not significantly contribute to bone strength at the non-weight bearing radius and was negatively associated with radius cortical content and thickness. Bone measures did not significantly differ between Hispanic and non-Hispanic girls, although there was a significant interaction between ethnicity and fat mass with total bone area at the femur (p = 0.02) and 66% tibia (p = 0.005) as well as bone strength at the femur (p = 0.03). Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic. Copyright © 2018. Published by Elsevier Inc.

Appendicular and whole body lean mass outcomes are associated with finite element analysis-derived bone strength at the distal radius and tibia in adults aged 40years and older.

PubMed

Gibbs, Jenna C; Giangregorio, Lora M; Wong, Andy K O; Josse, Robert G; Cheung, Angela M

2017-10-01

The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height 2 ), LMI (lean tissue mass/height 2 ) and FMI (fat mass/height 2 ) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m 2 , ALMI: 7.31±1.31kg/m 2 ), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R 2 =0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R 2 =0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

Adrenarche and bone modeling and remodeling at the proximal radius: weak androgens make stronger cortical bone in healthy children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela; Neu, Christina M; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2003-08-01

Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6-18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001)--reflecting, at least in part, reduction in intracortical remodeling-were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children.

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

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.; Smith, Scott A.; Hans, Didier; LeBlanc, Adrian; Spector, Elisabeth; Evans, Harlan; King, Lisa

2014-01-01

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.

New QCT analysis approach shows the importance of fall orientation on femoral neck strength.

PubMed

Carpenter, R Dana; Beaupré, Gary S; Lang, Thomas F; Orwoll, Eric S; Carter, Dennis R

2005-09-01

The influence of fall orientation on femur strength has important implications for understanding hip fracture risk. A new image analysis technique showed that the strength of the femoral neck in 37 males varied significantly along the neck axis and that bending strength varied by a factor of up to 2.8 for different loading directions. Osteoporosis is associated with decreased BMD and increased hip fracture risk, but it is unclear whether specific osteoporotic changes in the proximal femur lead to a more vulnerable overall structure. Nonhomogeneous beam theory, which is used to determine the mechanical response of composite structures to applied loads, can be used along with QCT to estimate the resistance of the femoral neck to axial forces and bending moments. The bending moment [My(theta)] sufficient to induce yielding within femoral neck sections was estimated for a range of bending orientations (theta) using in vivo QCT images of 37 male (mean age, 73 years; range, 65-87 years) femora. Volumetric BMD, axial stiffness, average moment at yield (M(y,avg)), maximum and minimum moment at yield (M(y,max) and M(y,min)), bone strength index (BSI), stress-strain index (SSI), and density-weighted moments of resistance (Rx and Ry) were also computed. Differences among the proximal, mid-, and distal neck regions were detected using ANOVA. My(theta) was found to vary by as much as a factor of 2.8 for different bending directions. Axial stiffness, M(y,avg), M(y,max), M(y,min), BSI, and Rx differed significantly between all femoral neck regions, with an overall trend of increasing axial stiffness and bending strength when moving from the proximal neck to the distal neck. Mean axial stiffness increased 62% between the proximal and distal neck, and mean M(y,avg) increased 53% between the proximal and distal neck. The results of this study show that femoral neck strength strongly depends on both fall orientation and location along the neck axis. Compressive yielding in the superior portion of the femoral neck is expected to initiate fracture in a fall to the side.

Decrease in local volumetric bone mineral density (vBMD) in osteoarthritic joints is associated with the increase in cartilage damage: a pQCT study

NASA Astrophysics Data System (ADS)

Tamaddon, Maryam; Chen, Shen Mao; Vanaclocha, Leyre; Hart, Alister; El-Husseiny, Moataz; Henckel, Johann; Liu, Chaozong

2017-11-01

Osteoarthritis (OA) is the most common type of arthritis and a major cause of disability in the adult population. It affects both cartilage and subchondral bone in the joints. There has been some progress in understanding the changes in subchondral bone with progression of osteoarthritis. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study we examined the volumetric bone mineral density (vBMD) distribution in the osteoarthritic joint tissues obtained from total hip replacement surgeries due to osteoarthritis, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in volumetric bone mineral density, which co-localises with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher volumetric bone mineral density than that of the surrounding bones. PQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

[New methods for the evaluation of bone quality. Assessment of bone structural property using imaging.

PubMed

Ito, Masako

Structural property of bone includes micro- or nano-structural property of the trabecular and cortical bone, and macroscopic geometry. Radiological technique is useful to analyze the bone structural property;multi-detector row CT(MDCT)or high-resolution peripheral QCT(HR-pQCT)is available to analyze human bone in vivo . For the analysis of hip geometry, CT-based hip structure analysis(HSA)is available as well as DXA-based HSA. These structural parameters are related to biomechanical property, and these assessment tools provide information of pathological changes or the effects of anti-osteoporotic agents on bone.

The prediction of cyclic proximal humerus fracture fixation failure by various bone density measures.

PubMed

Varga, Peter; Grünwald, Leonard; Windolf, Markus

2018-02-22

Fixation of osteoporotic proximal humerus fractures has remained challenging, but may be improved by careful pre-operative planning. The aim of this study was to investigate how well the failure of locking plate fixation of osteoporotic proximal humerus fractures can be predicted by bone density measures assessed with currently available clinical imaging (realistic case) and a higher resolution and quality modality (theoretical best-case). Various density measures were correlated to experimentally assessed number of cycles to construct failure of plated unstable low-density proximal humerus fractures (N = 18). The influence of density evaluation technique was investigated by comparing local (peri-implant) versus global evaluation regions; HR-pQCT-based versus clinical QCT-based image data; ipsilateral versus contralateral side; and bone mineral content (BMC) versus bone mineral density (BMD). All investigated density measures were significantly correlated with the experimental cycles to failure. The best performing clinically feasible parameter was the QCT-based BMC of the contralateral articular cap region, providing significantly better correlation (R 2  = 0.53) compared to a previously proposed clinical density measure (R 2  = 0.30). BMC had consistently, but not significantly stronger correlations with failure than BMD. The overall best results were obtained with the ipsilateral HR-pQCT-based local BMC (R 2  = 0.74) that may be used for implant optimization. Strong correlations were found between the corresponding density measures of the two CT image sources, as well as between the two sides. Future studies should investigate if BMC of the contralateral articular cap region could provide improved prediction of clinical fixation failure compared to previously proposed measures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Finite element analysis of a pseudoelastic compression-generating intramedullary ankle arthrodesis nail.

PubMed

Anderson, Ryan T; Pacaccio, Douglas J; Yakacki, Christopher M; Carpenter, R Dana

2016-09-01

Tibio-talo-calcaneal (TTC) arthrodesis is an end-stage treatment for patients with severe degeneration of the ankle joint. This treatment consists of using an intramedullary nail (IM) to fuse the calcaneus, talus, and tibia bones together into one construct. Poor bone quality within the joint prior to surgery is common and thus the procedure has shown complications due to non-union. However, a new FDA-approved IM nail has been released that houses a nickel titanium (NiTi) rod that uses its inherent pseudoelastic material properties to apply active compression across the fusion site. Finite element analysis was performed to model the mechanical response of the NiTi within the device. A bone model was then developed based on a quantitative computed tomography (QCT) image for anatomical geometry and bone material properties. A total bone and device system was modeled to investigate the effect of bone quality change and gather load-sharing properties during gait loading. It was found that during the highest magnitude loading of gait, the load taken by the bone was more than 50% higher than the load taken by the nail. When comparing the load distribution during gait, results from this study would suggest that the device helps to prevent stress shielding by allowing a more even distribution of load between bone and nail. In conditions where bone quality may vary patient-to-patient, the model indicates that a 10% decrease in overall bone modulus (i.e. material stiffness) due to reduced bone mineral density would result in higher stresses in the nail (3.4%) and a marginal decrease in stress for the bone (0.5%). The finite element model presented in this study can be used as a quantitative tool to further understand the stress environment of both bone and device for a TTC fusion. Furthermore, the methodology presented gives insight on how to computationally program and use the unique material properties of NiTi in an active compression state useful for bone fracture healing or fusion treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comparison of battery testing protocols: Those used by the U.S. advanced battery consortium and those used in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, David C.; Christophersen, Jon P.; Bennett, Taylor

Two testing protocols, QC/T 743 and those used by the U.S. Advanced Battery Consortium (USABC), were compared using cells based on LiFePO4/graphite chemistry. Differences in the protocols directly affected the data and the performance decline mechanisms deduced from the data. A change in capacity fade mechanism from linear-with-time to t1/2 was observed when the power density measurement was included in the QC/T 743 testing. The rate of resistance increase was linear with time using both protocols. Overall, the testing protocols produced very similar data when the testing conditions and metrics used to define performance were similar. The choice of depthmore » of discharge and pulse width had a direct effect on estimated cell life. At greater percent depth of discharge (%DOD) and pulse width, the estimated life was shorter that at lower %DOD and shorter pulse width. This indicates that cells which were at the end of life based on the USABC protocol were not at end of life based on the QC/T 743 protocol by a large margin.« less

The OH + D2 --> HOD + D angle-velocity distribution: quasi-classical trajectory calculations on the YZCL2 and WSLFH potential energy surfaces and comparison with experiments at ET = 0.28 eV.

PubMed

Sierra, José Daniel; Martínez, Rodrigo; Hernando, Jordi; González, Miguel

2009-12-28

The angle-velocity distribution (HOD) of the OH + D(2) reaction at a relative translational energy of 0.28 eV has been calculated using the quasi-classical trajectory (QCT) method on the two most recent potential energy surfaces available (YZCL2 and WSLFH PESs), widely extending a previous investigation of our group. Comparison with the high resolution experiments of Davis and co-workers (Science, 2000, 290, 958) shows that the structures (peaks) found in the relative translational energy distributions of products could not be satisfactorily reproduced in the calculations, probably due to the classical nature of the QCT method and the importance of quantum effects. The calculations, however, worked quite well for other properties. Overall, both surfaces led to similar results, although the YZCL2 surface is more accurate to describe the H(3)O PES, as derived from comparison with high level ab initio results. The differences observed in the QCT calculations were interpreted considering the somewhat larger anisotropy of the YZCL2 PES when compared with the WSLFH PES.

A Biomechanical Approach to Assessing Hip Fracture Risk

NASA Technical Reports Server (NTRS)

Ellman, Rachel

2009-01-01

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.

Maturity- and sex-related changes in tibial bone geometry, strength and bone-muscle strength indices during growth: a 20-month pQCT study.

PubMed

Macdonald, Heather M; Kontulainen, Saija A; Mackelvie-O'Brien, Kerry J; Petit, Moira A; Janssen, Patricia; Khan, Karim M; McKay, Heather A

2005-06-01

During growth, bone strength is conferred through subtle adaptations in bone mass and geometry in response to muscle forces. Few studies have examined the changes in bone geometry, strength and the bone-muscle strength relationship across maturity in boys and girls. Our aims were to describe (i) 20-month changes in bone geometry and strength at the tibial midshaft across three maturity groups of boys and girls, (ii) differences in these adaptations between sexes at the same approximate level of maturity and (iii) the bone-muscle strength relationship across maturity groups of boys and girls and between sexes. We used peripheral quantitative computed tomography (pQCT, Stratec XCT-2000) to measure change in total bone cross-sectional area (ToA, mm(2)), cortical area (CoA, mm(2)), average cortical thickness (C.Th., mm), section modulus (mm(3)) and muscle cross-sectional area (mm(2)) at the tibial midshaft (50% site) in 128 EARLY-, PERI- and POST-pubertal girls (n = 69, 11.9 +/- 0.6 years) and boys (n = 59, 12.0 +/- 0.6 years) across 20 months. We also calculated two bone-muscle strength indices (BMSI) for compression (CoA/MCSA) and bending [strength index/MCSA; where strength index = Z / (tibial length / 2)]. EARLY boys and girls had smaller ToA at baseline than same sex PERI or POST participants. There were no sex differences in ToA or CoA at baseline; however, boys increased both parameters significantly more than girls in every maturity group (8.5-11.1%, P < 0.01). These changes in bone geometry conferred greater gains in bone strength for boys compared with girls in each maturity group (13.8-15.6%, P < 0.01). Baseline BMSIs did not differ between sexes for EARLY and PERI groups, whereas BMSIs were significantly higher for POST boys compared with POST girls (P < 0.05). BMSIs decreased for EARLY and PERI girls (-7.4-(-1.1%)) whereas the ratios remained stable for EARLY and PERI boys (-0.6-2.5%). This sex difference in BMSI change was due to a relatively greater increase in CoA among EARLY and PERI boys compared with same-maturity girls. BMSIs remained stable in POST girls and decreased in POST boys due to relatively greater gains in MCSA. This study provides novel longitudinal descriptions of the maturity- and sex-specific changes in bone geometry, strength and bone-muscle strength indices.

Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

PubMed Central

Kähönen, Mika; Raitakari, Olli; Laaksonen, Marika; Sievänen, Harri; Viikari, Jorma; Lyytikäinen, Leo-Pekka; Mellström, Dan; Karlsson, Magnus; Ljunggren, Östen; Grundberg, Elin; Kemp, John P.; Sayers, Adrian; Nethander, Maria; Evans, David M.; Vandenput, Liesbeth; Tobias, Jon H.; Ohlsson, Claes

2013-01-01

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk. PMID:23437003

Type 2 Diabetes Mellitus Is Associated With Better Bone Microarchitecture But Lower Bone Material Strength and Poorer Physical Function in Elderly Women: A Population-Based Study.

PubMed

Nilsson, Anna G; Sundh, Daniel; Johansson, Lisa; Nilsson, Martin; Mellström, Dan; Rudäng, Robert; Zoulakis, Michail; Wallander, Märit; Darelid, Anna; Lorentzon, Mattias

2017-05-01

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75 to 80 years in Gothenburg, randomly invited from the population register. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n = 99) had higher aBMD compared to controls (n = 954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean ± SD: 1.5% ± 1.1% versus 2.0% ± 1.7%, p = 0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6 ± 7.6 versus 78.2 ± 7.5, p < 0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30-s chair-stand test: -7%, timed up and go: +12%, walking speed: +8%; p < 0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to nondiabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Evaluation de la qualite osseuse par les ondes guidees ultrasonores =

NASA Astrophysics Data System (ADS)

Abid, Alexandre

La caracterisation des proprietes mecaniques de l'os cortical est un domaine d'interet pour la recherche orthopedique. En effet, cette caracterisation peut apporter des informations primordiales pour determiner le risque de fracture, la presence de microfractures ou encore depister l'osteoporose. Les deux principales techniques actuelles de caracterisation de ces proprietes sont le Dual-energy X-ray Absorptiometry (DXA) et le Quantitative Computed Tomogaphy (QCT). Ces techniques ne sont pas optimales et presentent certaines limites, ainsi l'efficacite du DXA est questionnee dans le milieu orthopedique tandis que le QCT necessite des niveaux de radiations problematiques pour en faire un outil de depistage. Les ondes guidees ultrasonores sont utilisees depuis de nombreuses annees pour detecter les fissures, la geometrie et les proprietes mecaniques de cylindres, tuyaux et autres structures dans des milieux industriels. De plus, leur utilisation est plus abordable que celle du DXA et n'engendrent pas de radiation ce qui les rendent prometteuses pour detecter les proprietes mecaniques des os. Depuis moins de dix ans, de nombreux laboratoires de recherche tentent de transposer ces techniques au monde medical, en propageant les ondes guidees ultrasonores dans les os. Le travail presente ici a pour but de demontrer le potentiel des ondes guidees ultrasonores pour determiner l'evolution des proprietes mecaniques de l'os cortical. Il commence par une introduction generale sur les ondes guidees ultrasonores et une revue de la litterature des differentes techniques relatives a l'utilisation des ondes guidees ultrasonores sur les os. L'article redige lors de ma maitrise est ensuite presente. L'objectif de cet article est d'exciter et de detecter certains modes des ondes guides presentant une sensibilite a la deterioration des proprietes mecaniques de l'os cortical. Ce travail est realise en modelisant par elements finis la propagation de ces ondes dans deux modeles osseux cylindriques. Ces deux modeles sont composes d'une couche peripherique d'os cortical et remplis soit d'os trabeculaire soit de moelle osseuse. Ces deux modeles permettent d'obtenir deux geometries, chacune propice a la propagation circonferentielle ou longitudinale des ondes guidees. Les resultats, ou trois differents modes ont pu etre identifies, sont compares avec des donnees experimentales obtenues avec des fantomes osseux et theoriques. La sensibilite de chaque mode pour les differents parametres des proprietes mecaniques est alors etudiee ce qui permet de conclure sur le potentiel de chaque mode quant a la prediction de risque de fracture ou de presence de microfractures.

The Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Three year effects on pQCT bone mineral density and strength measures in postmenopausal women

PubMed Central

SHEDD-WISE, KRISTINE M.; ALEKEL, D. LEE; HOFMANN, HEIKE; HANSON, KATHY B.; SCHIFERL, DAN J.; HANSON, LAURA N.; VAN LOAN, MARTA D.

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined two soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (via peripheral quantitative computed tomography) in healthy postmenopausal women (46–63 y). We measured 3 y change in cortical (Ct) BMD, cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171) and trabecular (Tb) BMD, PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. Strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120 mg/d was protective of CtBMD. Strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80 mg/d became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3 y was modestly beneficial for midshaft femur vBMD as TLMP increased, and for midshaft femur SSI as bone turnover increased. PMID:21295742

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

PubMed Central

Gertz, ER; Silverman, NE; Wise, KS; Hanson, KB; Alekel, DL; Stewart, JW; Perry, CD; Bhupathiraju, SN; Kohut, ML; Van Loan, MD

2010-01-01

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content and density (BMC, BMD) and determined the contribution of inflammatory markers to 1-year changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss (SIRBL) project who were randomly assigned to one of three treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy x-ray absorptiometry (DXA) and the 4% distal tibia (DT) by peripheral quantitative computed tomography (pQCT). Serum inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and white blood cell count (WBC)) were measured at baseline, 6 and 12 months. Due to attrition or missing values, data analysis at 12 months includes only 235 women. Significant associations among Il-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1% to 6.1% of the variance to the observed 12 month changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss. PMID:20605499

In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

NASA Astrophysics Data System (ADS)

Ritter, Zully; Belavy, Daniel; Baumann, Wolfgang W.; Felsenberg, Dieter

2017-03-01

Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1 g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082 mm×0.082 mm×0.082 mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture).

A study of internal energy relaxation in shocks using molecular dynamics based models

NASA Astrophysics Data System (ADS)

Li, Zheng; Parsons, Neal; Levin, Deborah A.

2015-10-01

Recent potential energy surfaces (PESs) for the N2 + N and N2 + N2 systems are used in molecular dynamics (MD) to simulate rates of vibrational and rotational relaxations for conditions that occur in hypersonic flows. For both chemical systems, it is found that the rotational relaxation number increases with the translational temperature and decreases as the rotational temperature approaches the translational temperature. The vibrational relaxation number is observed to decrease with translational temperature and approaches the rotational relaxation number in the high temperature region. The rotational and vibrational relaxation numbers are generally larger in the N2 + N2 system. MD-quasi-classical trajectory (QCT) with the PESs is also used to calculate the V-T transition cross sections, the collision cross section, and the dissociation cross section for each collision pair. Direct simulation Monte Carlo (DSMC) results for hypersonic flow over a blunt body with the total collision cross section from MD/QCT simulations, Larsen-Borgnakke with new relaxation numbers, and the N2 dissociation rate from MD/QCT show a profile with a decreased translational temperature and a rotational temperature close to vibrational temperature. The results demonstrate that many of the physical models employed in DSMC should be revised as fundamental potential energy surfaces suitable for high temperature conditions become available.

Multipolar electrostatics for proteins: atom-atom electrostatic energies in crambin.

PubMed

Yuan, Yongna; Mills, Matthew J L; Popelier, Paul L A

2014-02-15

Accurate electrostatics necessitates the use of multipole moments centered on nuclei or extra point charges centered away from the nuclei. Here, we follow the former alternative and investigate the convergence behavior of atom-atom electrostatic interactions in the pilot protein crambin. Amino acids are cut out from a Protein Data Bank structure of crambin, as single amino acids, di, or tripeptides, and are then capped with a peptide bond at each side. The atoms in the amino acids are defined through Quantum Chemical Topology (QCT) as finite volume electron density fragments. Atom-atom electrostatic energies are computed by means of a multipole expansion with regular spherical harmonics, up to a total interaction rank of L = ℓA+ ℓB + 1 = 10. The minimum internuclear distance in the convergent region of all the 15 possible types of atom-atom interactions in crambin that were calculated based on single amino acids are close to the values calculated from di and tripeptides. Values obtained at B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels are only slightly larger than those calculated at HF/6-31G(d,p) level. This convergence behavior is transferable to the well-known amyloid beta polypeptide Aβ1-42. Moreover, for a selected central atom, the influence of its neighbors on its multipole moments is investigated, and how far away this influence can be ignored is also determined. Finally, the convergence behavior of AMBER becomes closer to that of QCT with increasing internuclear distance. Copyright © 2013 Wiley Periodicals, Inc.

Determinants of exercise-induced oxygen desaturation including pulmonary emphysema in COPD: Results from the ECLIPSE study.

PubMed

Andrianopoulos, Vasileios; Celli, Bartolome R; Franssen, Frits M E; Pinto-Plata, Victor M; Calverley, Peter M A; Vanfleteren, Lowie E G W; Vogiatzis, Ioannis; Vestbo, Jørgen; Agusti, Alvar; Bakke, Per S; Rennard, Stephen I; MacNee, William; Tal-Singer, Ruth; Yates, Julie C; Wouters, Emiel F M; Spruit, Martijn A

2016-10-01

Exercise-induced oxygen desaturation (EID) is related to mortality in patients with chronic obstructive pulmonary disease (COPD). We investigated: (1) the prevalence of EID; (2) the relative-weight of several physiological determinants of EID including pulmonary emphysema, and (3) the relationship of EID with certain patients' clinical characteristics. Data from 2050 COPD patients (age: 63.3 ± 7.1years; FEV 1 : 48.7 ± 15.7%pred.) were analyzed. The occurrence of EID (SpO 2 post ≤88%) at the six-minute walking test (6MWT) was investigated in association with emphysema quantified by computed-tomography (QCT), and several clinical characteristics. 435 patients (21%) exhibited EID. Subjects with EID had more QCT-emphysema, lower exercise capacity and worse health-status (BODE, ADO indexes) compared to non-EID. Determinant of EID were obesity (BMI≥30 kg/m 2 ), impaired FEV 1 (≤44%pred.), moderate or worse emphysema, and low SpO 2 at rest (≤93%). Linear regression indicated that each 1-point increase on the ADO-score independently elevates odds ratio (≤1.5fold) for EID. About one in five COPD patients in the ECLIPSE cohort present EID. Advanced emphysema is associated with EID. In addition, obesity, severe airflow limitation, and low resting oxygen saturation increase the risk for EID. Patients with EID in GOLD stage II have higher odds to have moderate or worse emphysema compared those with EID in GOLD stage III-IV. Emphysematous patients with high ADO-score should be monitored for EID. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rate coefficients of exchange reactions accounting for vibrational excitation of reagents and products

NASA Astrophysics Data System (ADS)

Kustova, E. V.; Savelev, A. S.; Kunova, O. V.

2018-05-01

Theoretical models for the vibrational state-resolved Zeldovich reaction are assessed by comparison with the results of quasi-classical trajectory (QCT) calculations. An error in the model of Aliat is corrected; the model is generalized taking into account NO vibrational states. The proposed model is fairly simple and can be easily implemented to the software for non-equilibrium flow modeling. It provides a good agreement with the QCT rate coefficients in the whole range of temperatures and reagent/product vibrational states. The developed models are tested in simulations of vibrational and chemical relaxation of air mixture behind a shock wave. The importance of accounting for excitated NO vibrational states and accurate prediction of Zeldovich reactions rates is shown.

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

PubMed

Gooi, J H; Pompolo, S; Karsdal, M A; Kulkarni, N H; Kalajzic, I; McAhren, S H M; Han, B; Onyia, J E; Ho, P W M; Gillespie, M T; Walsh, N C; Chia, L Y; Quinn, J M W; Martin, T J; Sims, N A

2010-06-01

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously unsuspected mechanism. Copyright 2010 Elsevier Inc. All rights reserved.

Rate coefficients from quantum and quasi-classical cumulative reaction probabilities for the S(1D) + H2 reaction

NASA Astrophysics Data System (ADS)

Jambrina, P. G.; Lara, Manuel; Menéndez, M.; Launay, J.-M.; Aoiz, F. J.

2012-10-01

Cumulative reaction probabilities (CRPs) at various total angular momenta have been calculated for the barrierless reaction S(1D) + H2 → SH + H at total energies up to 1.2 eV using three different theoretical approaches: time-independent quantum mechanics (QM), quasiclassical trajectories (QCT), and statistical quasiclassical trajectories (SQCT). The calculations have been carried out on the widely used potential energy surface (PES) by Ho et al. [J. Chem. Phys. 116, 4124 (2002), 10.1063/1.1431280] as well as on the recent PES developed by Song et al. [J. Phys. Chem. A 113, 9213 (2009), 10.1021/jp903790h]. The results show that the differences between these two PES are relatively minor and mostly related to the different topologies of the well. In addition, the agreement between the three theoretical methodologies is good, even for the highest total angular momenta and energies. In particular, the good accordance between the CRPs obtained with dynamical methods (QM and QCT) and the statistical model (SQCT) indicates that the reaction can be considered statistical in the whole range of energies in contrast with the findings for other prototypical barrierless reactions. In addition, total CRPs and rate coefficients in the range of 20-1000 K have been calculated using the QCT and SQCT methods and have been found somewhat smaller than the experimental total removal rates of S(1D).

Precision of pQCT-measured total, trabecular and cortical bone area, content, density and estimated bone strength in children

PubMed Central

Duff, W.R.D.; Björkman, K.M.; Kawalilak, C.E.; Kehrig, A.M.; Wiebe, S.; Kontulainen, S.

2017-01-01

Objectives: To define pQCT precision errors, least-significant-changes, and identify associated factors for bone outcomes at the radius and tibia in children. Methods: We obtained duplicate radius and tibia pQCT scans from 35 children (8-14yrs). We report root-mean-squared coefficient of variation (CV%RMS) and 95% limits-of-agreement to characterize repeatability across scan quality and least-significant-changes for bone outcomes at distal (total and trabecular area, content and density; and compressive bone strength) and shaft sites (total area and content; cortical area content, density and thickness; and torsional bone strength). We used Spearman’s rho to identify associations between CV% and time between measurements, child’s age or anthropometrics. Results: After excluding unanalyzable scans (6-10% of scans per bone site), CV%RMS ranged from 4% (total density) to 19% (trabecular content) at the distal radius, 4% (cortical content) to 8% (cortical thickness) at the radius shaft, 2% (total density) to 14% (trabecular content) at the distal tibia and from 2% (cortical content) to 6% (bone strength) at the tibia shaft. Precision errors were within 95% limits-of-agreement across scan quality. Age was associated (rho -0.4 to -0.5, p <0.05) with CV% at the tibia. Conclusion: Bone density outcomes and cortical bone properties appeared most precise (CV%RMS <5%) in children. PMID:28574412

Prevalence of vitamin D insufficiency among adolescents and its correlation with bone parameters using high-resolution peripheral quantitative computed tomography.

PubMed

Cheung, T F; Cheuk, K Y; Yu, F W P; Hung, V W Y; Ho, C S; Zhu, T Y; Ng, B K W; Lee, K M; Qin, L; Ho, S S Y; Wong, G W K; Cheng, J C Y; Lam, T P

2016-08-01

Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. Three hundred thirty-three girls and 230 boys (12-16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D < 25 nmol/L] in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels. Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.

Body Composition Remodeling and Incident Mobility Limitations in African Ancestry Men.

PubMed

Santanasto, Adam J; Miljkovic, Iva; Cvejkus, Ryan C; Gordon, Christopher L; Bunker, Clareann H; Patrick, Allen L; Wheeler, Victor W; Zmuda, Joseph M

2018-04-05

Mobility limitations are common, with higher prevalence in African Americans compared to whites, and are associated with disability, institutionalization and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African Ancestry. Seven-year changes in body composition were measured using peripheral computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African Ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. Seventy-five men (14.9%) developed incident mobility limitations over 6.2±0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations a (OR: 1.60; 95% CI: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

Sex differences and growth-related adaptations in bone microarchitecture, geometry, density and strength from childhood to early adulthood: a mixed longitudinal HR-pQCT study

PubMed Central

Gabel, Leigh; Macdonald, Heather M.; McKay, Heather A.

2016-01-01

Sex differences in bone strength and fracture risk are well-documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density and geometry that accompany gains in bone strength. Thus, our objectives are to 1) describe growth related adaptations in bone microarchitecture, geometry, density and strength at the distal tibia and radius in boys and girls; 2) compare differences in adaptations in bone microarchitecture, geometry, density and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9–20y at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity; APHV) and fit a mixed effects model to these longitudinal data. Importantly, boys demonstrated 28–63% greater estimated bone strength across 12 years of longitudinal growth. Boys demonstrated 28–80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls’ values were 2% greater than boys’. Boys demonstrated 13–48% greater cortical and total bone area across growth. Load-to-strength ratio was 26–27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to boys’ higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. PMID:27556581

The non-statistical dynamics of the 18O + 32O2 isotope exchange reaction at two energies

NASA Astrophysics Data System (ADS)

Van Wyngarden, Annalise L.; Mar, Kathleen A.; Quach, Jim; Nguyen, Anh P. Q.; Wiegel, Aaron A.; Lin, Shi-Ying; Lendvay, Gyorgy; Guo, Hua; Lin, Jim J.; Lee, Yuan T.; Boering, Kristie A.

2014-08-01

The dynamics of the 18O(3P) + 32O2 isotope exchange reaction were studied using crossed atomic and molecular beams at collision energies (Ecoll) of 5.7 and 7.3 kcal/mol, and experimental results were compared with quantum statistical (QS) and quasi-classical trajectory (QCT) calculations on the O3(X1A') potential energy surface (PES) of Babikov et al. [D. Babikov, B. K. Kendrick, R. B. Walker, R. T. Pack, P. Fleurat-Lesard, and R. Schinke, J. Chem. Phys. 118, 6298 (2003)]. In both QS and QCT calculations, agreement with experiment was markedly improved by performing calculations with the experimental distribution of collision energies instead of fixed at the average collision energy. At both collision energies, the scattering displayed a forward bias, with a smaller bias at the lower Ecoll. Comparisons with the QS calculations suggest that 34O2 is produced with a non-statistical rovibrational distribution that is hotter than predicted, and the discrepancy is larger at the lower Ecoll. If this underprediction of rovibrational excitation by the QS method is not due to PES errors and/or to non-adiabatic effects not included in the calculations, then this collision energy dependence is opposite to what might be expected based on collision complex lifetime arguments and opposite to that measured for the forward bias. While the QCT calculations captured the experimental product vibrational energy distribution better than the QS method, the QCT results underpredicted rotationally excited products, overpredicted forward-bias and predicted a trend in the strength of forward-bias with collision energy opposite to that measured, indicating that it does not completely capture the dynamic behavior measured in the experiment. Thus, these results further underscore the need for improvement in theoretical treatments of dynamics on the O3(X1A') PES and perhaps of the PES itself in order to better understand and predict non-statistical effects in this reaction and in the formation of ozone (in which the intermediate O3* complex is collisionally stabilized by a third body). The scattering data presented here at two different collision energies provide important benchmarks to guide these improvements.

Rapid 3D bioprinting from medical images: an application to bone scaffolding

NASA Astrophysics Data System (ADS)

Lee, Daniel Z.; Peng, Matthew W.; Shinde, Rohit; Khalid, Arbab; Hong, Abigail; Pennacchi, Sara; Dawit, Abel; Sipzner, Daniel; Udupa, Jayaram K.; Rajapakse, Chamith S.

2018-03-01

Bioprinting of tissue has its applications throughout medicine. Recent advances in medical imaging allows the generation of 3-dimensional models that can then be 3D printed. However, the conventional method of converting medical images to 3D printable G-Code instructions has several limitations, namely significant processing time for large, high resolution images, and the loss of microstructural surface information from surface resolution and subsequent reslicing. We have overcome these issues by creating a JAVA program that skips the intermediate triangularization and reslicing steps and directly converts binary dicom images into G-Code. In this study, we tested the two methods of G-Code generation on the application of synthetic bone graft scaffold generation. We imaged human cadaveric proximal femurs at an isotropic resolution of 0.03mm using a high resolution peripheral quantitative computed tomography (HR-pQCT) scanner. These images, of the Digital Imaging and Communications in Medicine (DICOM) format, were then processed through two methods. In each method, slices and regions of print were selected, filtered to generate a smoothed image, and thresholded. In the conventional method, these processed images are converted to the STereoLithography (STL) format and then resliced to generate G-Code. In the new, direct method, these processed images are run through our JAVA program and directly converted to G-Code. File size, processing time, and print time were measured for each. We found that this new method produced a significant reduction in G-Code file size as well as processing time (92.23% reduction). This allows for more rapid 3D printing from medical images.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

PubMed

Shedd-Wise, Kristine M; Alekel, D Lee; Hofmann, Heike; Hanson, Kathy B; Schiferl, Dan J; Hanson, Laura N; Van Loan, Marta D

2011-01-01

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Methods and procedures for: A randomized double-blind study investigating dose-dependent longitudinal effects of vitamin D supplementation on bone health.

PubMed

Burt, Lauren A; Gaudet, Sharon; Kan, Michelle; Rose, Marianne S; Billington, Emma O; Boyd, Steven K; Hanley, David A

2018-04-01

The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD) concentration for bone health is still debated and some health practitioners are recommending doses well above the Canada/USA recommended Dietary Reference Intake (DRI). We designed a three-year randomized double-blind clinical trial investigating whether there are dose-dependent effects of vitamin D supplementation above the Dietary Reference Intake (DRI) on bone health. The primary aims of this study are to assess, whether supplementation of vitamin D 3 increases 1) volumetric bone mineral density measured by high-resolution peripheral quantitative computed tomography (HR-pQCT); 2) bone strength assessed by finite element analysis, and 3) areal bone mineral density by dual X-ray absorptiometry (DXA). Secondary aims are to understand whether vitamin D 3 supplementation improves parameters of bone microarchitecture, balance, physical function and quality of life. Participants are men and women aged 55-70 years, with women at least 5-years post-menopause. The intervention is daily vitamin D 3 supplementation doses of 400, 4000 or 10,000 IU. Participants not achieving adequate dietary calcium intake are provided with calcium supplementation, up to a maximum supplemental dose of 600 mg elemental calcium per day. Results from this three-year study will provide evidence whether daily vitamin D 3 supplementation with adequate calcium intake can affect bone density, bone microarchitecture and bone strength in men and women. Furthermore, the safety of high dose daily vitamin D 3 supplementation will be explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nurmio, Mirja, E-mail: Mirja.Nurmio@utu.fi; Department of Pediatrics, University of Turku; Joki, Henna, E-mail: Henna.Joki@utu.fi

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bonemore » physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.« less

Zone-dependent changes in human vertebral trabecular bone: clinical implications.

PubMed

Thomsen, Jesper Skovhus; Ebbesen, E N; Mosekilde, Li

2002-05-01

We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates. The aim of the present study was, therefore, to investigate whether such zone-specific differences could be identified by static histomorphometric measures. The material comprised 48 individuals (24 women aged 19-97 years, and 24 men aged 23-95 years). Three of the women had a known fracture of the L-2. From each L-2, thick frontal sections of half of the vertebra were embedded undecalcified in methylmethacrylate, cut into 10-microm-thick sections, and stained with aniline blue. The sections were scanned into a computer, and classic static histomorphometry was performed on the images. The histomorphometry was performed on both the whole section and on the separate zones (central and sub-endplate zone). The results showed that trabecular bone volume, trabecular number, and connectivity density decreased significantly faster with age, whereas marrow space star volume increased significantly faster with age in the zones adjacent to the endplates than in the central zone. The other histomorphometric measures showed no zone specificity in relation to aging. However, trabecular thickness and trabecular separation were both higher at all ages in the central zone than in the sub-endplate zone, although this was significant only for trabecular separation. The described differences might have significant clinical implications concerning quantitative computed tomography (QCT) scanning, X-ray analyses, and assessment of fracture liability in the human spine, but the underlying pathogenesis is still not known. This study shows that the human vertebral body can be described as two distinct zones with very specific age-related changes in density and microstructure. This zone-specificity is important for the correct interpretation of clinical data.

Quasi-Classical Trajectory Dynamics Study of the Cl(2P) + C2H6 → HCl(v,j) + C2H5 Reaction. Comparison with Experiment.

PubMed

Espinosa-Garcia, Joaquin; Martinez-Nuñez, Emilio; Rangel, Cipriano

2018-03-15

To understand and simulate the dynamics behavior of the title reaction, QCT calculations were performed on a recently developed global analytical potential energy surface, PES-2017. These calculations combine the classical description of the dynamics with pseudoquantization in the reactants and products to perform a theoretical/experimental comparison on the same footing. Thus, in the products a series of constraints are included to analyze the HCl(v = 0,j) product, which is experimentally detected. At collision energies of 5.5 and 6.7 kcal mol -1 the largest fraction of available energy is deposited as translation, 67%, while the ethyl radical shows significant internal energy, 27%, and so it does not act as a spectator of the reaction, thus reproducing recent experimental evidence. The HCl(v=0, j) rotational distribution is cold, peaking at j = 2, only one unit hotter than experiment, which represents an error of 0.12 kcal mol -1 . At a collision energy of 5.5 kcal mol -1 product translational distribution is slightly hotter than experiment, but at 6.7 kcal mol -1 agreement with recent experiments is practically quantitative, suggesting that the first experiments should be revised. In addition, we observe that the HCl(v=0, j) scattering distribution shifts from isotropic at low values of j to backward at high values of j, which is in agreement with experimental data. Finally, no evidence was found for the "chattering" mechanism suggested to explain the low translational energy of the HCl product in the backward scattering region. In sum, agreement with experiments of a series of sensible dynamic properties permits us to be optimistic on the quality and accuracy of the theoretical tools used in the present work, QCT and PES-2017.

Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lekadir, Karim, E-mail: karim.lekadir@upf.edu; Hoogendoorn, Corné; Armitage, Paul

Purpose: This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. Methods: A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by usingmore » a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. Results: Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. Conclusions: The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth.« less

Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

PubMed

Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

2013-09-01

To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. Copyright © 2013 Elsevier B.V. All rights reserved.

Quinazoline clubbed 1,3,5-triazine derivatives as VEGFR2 kinase inhibitors: design, synthesis, docking, in vitro cytotoxicity and in ovo antiangiogenic activity.

PubMed

Pathak, Prateek; Shukla, Parjanya Kumar; Kumar, Vikas; Kumar, Ankit; Verma, Amita

2018-04-16

A series of quinazoline clubbed 1,3,5-triazine derivatives (QCT) were synthesized and evaluated for their in vitro anticancer activity against HeLa (human cervical cancer), MCF-7 (human breast cancer cell), HL-60 (human promyelocytic leukemia cell), HepG2 (human Hepatocellular carcinoma cell), and one normal cell line HFF (human foreskin fibroblasts). In vitro assay result encouraged to further move towards in ovo anticancer evaluation using chick embryo. The series of QCT derivatives showed higher anticancer and antiangiogenic activity against HeLa and MCF-7 cell lines. In the series, synthetic molecule 8d, 8l, and 8m displayed significant activity. Further, these results substantiated by docking study on VGFR2. SAR study concluded that the potency of drugs depends on the nature of aliphatic substitution and the heterocyclic ring system.

Estimation of in vivo cortical bone thickness using ultrasonic waves.

PubMed

Mano, Isao; Horii, Kaoru; Hagino, Hiroshi; Miki, Takami; Matsukawa, Mami; Otani, Takahiko

2015-07-01

To verify the measurement of cortical bone thickness at the distal radius in vivo using an ultrasonic method. The method for estimating cortical bone thickness was derived from experiments with in vitro bovine specimens. Propagation time of echo waves and propagation time of slow waves were used for the estimation. The outside diameter of cortical bone and the cortical bone thickness at the distal 5.5 % site of radius were measured with the new ultrasonic bone measurement system, and the results were compared with X-ray pQCT clinical measurements. There was a high positive correlation (r: 0.76) between the cortical bone thickness measured by the new ultrasonic system and the X-ray pQCT results. We will be able to measure not only cancellous bone density but also cortical bone thickness in vivo using ultrasonic waves (without X-ray) safely and repeatedly.

The effect of quercetin dietary supplementation on meat oxidation processes and texture of fattening lambs.

PubMed

Andrés, S; Huerga, L; Mateo, J; Tejido, M L; Bodas, R; Morán, L; Prieto, N; Rotolo, L; Giráldez, F J

2014-02-01

Thirty two lambs were fed a total mixed ration (TMR) formulated either with palm oil (CTRL; 34 g palm oil kg(-1) TMR) or whole flaxseed (+FS, 85 g flaxseed kg(-1) TMR) alone or enriched with quercetin (+QCT, 34 g palm oil plus 2 g quercetin kg(-1) TMR; +FS+QCT, 85 g flaxseed plus 2 g quercetin kg(-1) TMR). Dietary flaxseed did not affect, in a significant manner, the lipid peroxidation of meat samples. Quercetin treatment reduced oxysterol content (P<0.05) after 7 days of refrigerated storage of fresh meat, but did not affect significantly (P>0.05) the level of lipid-derived volatiles in the headspace of the light-exposed stored cooked meat. Sensory evaluation showed flaxseed as being responsible for a negative effect on meat flavour, probably associated with a modification of the fatty acid profile whereas, unexpectedly, quercetin seemed to worsen meat tenderisation. © 2013.

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2002-12-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and DXA. The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The used pQCT variables were bone mineral content (BMC), total cross-sectional area (TotA) of bone, cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index (BSIt) for the shaft, and compressional bone strength index (BSIc) for the bone end. These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater BMC (an average 19% side-to-side difference in young starters and 9% in old starters) was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites) leading to 26% and 11% side-to-side BSIt difference in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' BMC, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' BMC, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side BMC, TrD, and aBMD differences only; the young starters' BMC difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups the structural adaptation of the humeral shaft to long-term loading seemed to be achievedthrough periosteal enlargement of the bone cortex although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends also the TrD could be a modifiable factor to build a stronger bone structure. The conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, measuring two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

A STUDY ON THE HIERARCHY OF MANAGEMENT ELEMENTS

NASA Astrophysics Data System (ADS)

Suzuki, Nobuyuki; Watanabe, Tadashi

Compared to the late 20th century, the Japanese construction industry has drastically changed its business methodology, outlook and approach in response to global issues and the incredible advances in technology. Such influences, non-exhaustively include the; WTO Government procurement agreement, updating conditions of tendering and contracting, client demands for cost reduction and the rapid penetration of ICT (Information and Communication Technology) into modern society. These days, the significance of controlling Quality, Cost and Time (the so-called QCT) has been recognized as an eternal-triangle by almost all countries, Government organizations and the private sector. However, as the construction industry is exposed to , and influenced by, more and more internal and external dynamic factors, continued reliance on managing and controlling QCT elements on their own is no longer adequate in meeting the growing demands and expectations, and as such control of additional management elements is now essential to avoid problems, or minimize their potential impacts should they occur. This paper utilizes the results of a survey carried out amongst construction managers and consultants in Japan and overseas to develop a spatial network that defines the interaction of management factors as a weighted graphical model. The calculated closeness centrality index of the developed management network model is adopted to identify the initialelement hierarchy, which is then further analyzed using the minimum distance of independent relationships of management elements (Warshall-Floyd algorism methodology), to identify the optimum potential hierarchy for effective construction management. A key result of the analysis is the significance of "Human Resource" in the construction industry management element hierarchy alongside the traditional QCT elements.

Stereodynamics of the reactions: F + H2/HD/HT→FH + H/D/T

NASA Astrophysics Data System (ADS)

Chi, Xiao-Lin; Zhao, Jin-Feng; Zhang, Yong-Jia; Ma, Feng-Cai; Li, Yong-Qing

2015-05-01

Among many kinds of ways to study the properties of atom and molecule collision, the quasi-classical trajectory (QCT) method is an effective one to investigate the molecular reaction dynamics. QCT calculations have been carried out to investigate the stereodynamics of the reactions F + H2/HD/HT→FH + H/D/T, which proceed on the lowest-lying electronic states of the FH2 system based on the potential energy surface (PES) of the 12A’ FH2 ground state. Although the QCT method cannot describe all quantum effects in the process of the reaction, it has unique advantages when facing a three-atoms system or complicated polyatomic systems. Differential cross sections (DCSs) and three angle distribution functions P(θr), P(ϕr), P(θr, ϕr) on the PES at the collision of 2.74 kcal/mol have been investigated. The isotope effect becomes more obvious with the reagent molecule H2 turning into HD and HT. P(θr, ϕr), as the joint probability density function of both polar angles θr and ϕr, can reflect the properties of three-dimensional dynamic more intuitively. Project supported by the National Natural Science Foundation of China (Grant No. 11474141), the Scientific Research Foundation for the Returned Overseas Chinese Scholars (Grant No. 2014-1685), the Scientific Research Foundation for the Doctor of Liaoning University, the Special Fund Based Research New Technology of Methanol Conversion and Coal Instead of Oil, and the China Postdoctoral Science Foundation (Grant No. 2014M550158).

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

PubMed

Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

2007-05-01

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p

Effect of nickel-titanium shape memory metal alloy on bone formation.

PubMed

Kapanen, A; Ryhänen, J; Danilov, A; Tuukkanen, J

2001-09-01

The aim of this study was to determine the biocompatibility of NiTi alloy on bone formation in vivo. For this purpose we used ectopic bone formation assay which goes through all the events of bone formation and calcification. Comparisons were made between Nitinol (NiTi), stainless steel (Stst) and titanium-aluminium (6%)-vanadium (4%) alloy (Ti-6Al-4V), which were implanted for 8 weeks under the fascia of the latissimus dorsi muscle in 3-month-old rats. A light-microscopic examination showed no chronic inflammatory or other pathological findings in the induced ossicle or its capsule. New bone replaced part of the decalcified matrix with mineralized new cartilage and bone. The mineral density was measured with peripheral quantitative computed tomography (pQCT). The total bone mineral density (BMD) values were nearly equal between the control and the NiTi samples, the Stst samples and the Ti-6Al-4V samples had lower BMDs. Digital image analysis was used to measure the combined area of new fibrotic tissue and original implanted bone matrix powder around the implants. There were no significant differences between the implanted materials, although Ti-6Al-4V showed the largest matrix powder areas. The same method was used for measurements of proportional cartilage and new bone areas in the ossicles. NiTi showed the largest cartilage area (p < or = 0.05). Between implant groups the new bone area was largest in NiTi. We conclude that NiTi has good biocompatibility, as its effects on ectopic bone formation are similar to those of Stst, and that the ectopic bone formation assay developed here can be used for biocompatibility studies.

Bone microarchitecture of the tibial plateau in skeletal health and osteoporosis.

PubMed

Krause, Matthias; Hubert, Jan; Deymann, Simon; Hapfelmeier, Alexander; Wulff, Birgit; Petersik, Andreas; Püschel, Klaus; Amling, Michael; Hawellek, Thelonius; Frosch, Karl-Heinz

2018-05-07

Impaired bone structure poses a challenge for the treatment of osteoporotic tibial plateau fractures. As knowledge of region-specific structural bone alterations is a prerequisite to achieving successful long-term fixation, the aim of the current study was to characterize tibial plateau bone structure in patients with osteoporosis and the elderly. Histomorphometric parameters were assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 21 proximal tibiae from females with postmenopausal osteoporosis (mean age: 84.3 ± 4.9 years) and eight female healthy controls (45.5 ± 6.9 years). To visualize region-specific structural bony alterations with age, the bone mineral density (Hounsfield units) was additionally analyzed in 168 human proximal tibiae. Statistical analysis was based on evolutionary learning using globally optimal regression trees. Bone structure deterioration of the tibial plateau due to osteoporosis was region-specific. Compared to healthy controls (20.5 ± 4.7%) the greatest decrease in bone volume fraction was found in the medio-medial segments (9.2 ± 3.5%, p < 0.001). The lowest bone volume was found in central segments (tibial spine). Trabecular connectivity was severely reduced. Importantly, in the anterior and posterior 25% of the lateral and medial tibial plateaux, trabecular support and subchondral cortical bone thickness itself were also reduced. Thinning of subchondral cortical bone and marked bone loss in the anterior and posterior 25% of the tibial plateau should require special attention when osteoporotic patients require fracture fixation of the posterior segments. This knowledge may help to improve the long-term, fracture-specific fixation of complex tibial plateau fractures in osteoporosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

2002-01-01

The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Nakanishi, Yasutomo; Nishikawa, Satoshi; Kayasuga, Ryoji; Kawada, Naoki; Kunishige, Akiko; Hashimoto, Yasuaki; Tanaka, Makoto; Sugitani, Masafumi; Kawabata, Kazuhito

2014-08-01

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between CATSPERB, NR5A2 gene polymorphisms and Peak Bone Mineral Density in College Students in China

PubMed Central

Zhao, Yuan; Liu, Wenya; HUA, Ma; Shi, Raoni; Wang, Haitao; Yang, Wen

2014-01-01

Abstract Background Peak bone mineral density (PBMD) is influenced by both genetic and environmental factors, genes explains most of variation. As the novel candidate genes CATSPERB and NR5A2 may have been associated with spinal PBMD in adult. This study was to investigate the relationship among these two genes^ PBMD and the life style factors in young female. Methods The rs1298989 single nucleotide polymorphism (SNP) of the CATSPERB gene and the rs3762397 SNP of the NR5A2 gene were genotyped using SNaPshot® in 359 students from Xinjiang. The prospective study included 203 Han and 156 Uyghur subjects. PBMD was measured using quantitative computed tomography (QCT). Calcium, phosphate and alkaline phosphatase were measured by ELISA method. Physical activity, dietary calcium and life styles were assessed by questionnaire. Results Both SNPs showed differences in genotype and allele frequencies (P < 0.05) between the Han and Uyghur subjects. Total calcium intake, energy intake, tea and milk intake were also significantly different between two groups (P < 0.05). Multiple regression analysis showed an association between PBMD and vitamin D intake (P = 0.000), milk (P = 0.000), exercise (P = 0.029), rs1298989 (P = 0.028), energy intake (P = 0.043). Conclusion This study demonstrated the polymorphisms of the rs1298989 and rs3762397 are associated with PBMD both in Han and Uyghur subjects. PBMD, in Xinjiang, appears to be associated with several known factors that are well described in the literature. While the genotypes of rs1298989 and rs3762397 do not appear have a strong effect on the PBMD. PMID:25927035

Comparisons of bone mineral density and bone quality in adult rock climbers, resistance-trained men, and untrained men.

PubMed

Sherk, Vanessa D; Bemben, Michael G; Bemben, Debra A

2010-09-01

The nature of muscular contractions and episodes of impact loading during technical rock climbing are often varied and complex, and the resulting effects on bone health are unclear. The purpose of this study was to compare total body, lumbar spine, proximal femur, and forearm areal bone mineral density (aBMD) and tibia and forearm bone quality in male rock climbers (RC) (n = 15), resistance trained men (RT) (n = 16), and untrained male controls (CTR) (n = 16). Total body, anteroposterior (AP) lumbar spine, proximal femur, and forearm aBMD and body composition were measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, v. 10.50.086; GE Healthcare, Waukesha, Wisconsin, U.S.A.). Volumetric BMD (vBMD), bone content, bone area, and muscle cross-sectional area (MCSA) of the tibia and forearm were measured using pQCT (peripheral quantitative computed tomography; Stratec XCT 3000, Pforzheim, Germany). No significant group differences were seen in bone-free lean body mass. CTR had significantly (p < 0.05) greater body fat % than RC and RT and significantly (p < 0.05) greater fat mass than RC. Lumbar spine and femoral neck aBMD were significantly (p < 0.05) greater in RT compared to both RC and CTR. RC had significantly (p < 0.05) lower aBMD at the 33% radius site than CTR. Forearm MCSA was significantly (p < 0.05) lower in CTR than in the other groups. No significant differences were seen between groups for vBMD or bone area of the tibia and forearm. In conclusion, resistance-trained men had higher bone density at the central skeletal sites than rock climbers; however, bone quality variables of the peripheral limbs were similar in rock climber and resistance-trained groups.

Trabecular bone deficits among Vietnamese immigrants.

PubMed

Melton, L J; Marquez, M A; McCready, L K; Achenbach, S J; Riggs, B L; Amin, S; Khosla, S

2011-05-01

Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Twenty Vietnamese immigrants (age, 44-79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study.

Trabecular bone deficits among Vietnamese immigrants

PubMed Central

Marquez, M. A.; McCready, L. K.; Achenbach, S. J.; Riggs, B. L.; Amin, S.; Khosla, S.

2011-01-01

Summary Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels. Introduction The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques. Methods Twenty Vietnamese immigrants (age, 44–79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women). Results The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women. Conclusions Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study. PMID:20658128

Quantifying Bone–relevant Activity and its Relation to Bone Strength in Girls

PubMed Central

Farr, Joshua N.; Lee, Vinson R.; Blew, Robert M.; Lohman, Timothy G.; Going, Scott B.

2011-01-01

Physical activity (PA) is critical for maximizing bone development during growth. However, there is no consensus on how well existing PA measurement tools predict bone strength. PURPOSE Compare four methods of quantifying physical activity (PA) (pedometer, 3-day physical activity recall (3DPAR), bone-specific physical activity questionnaire (BPAQ), and past year physical activity questionnaire (PYPAQ)), in young girls and evaluate their ability to predict indices of bone strength. METHODS 329 girls aged 8–13 years completed a pedometer assessment, the 3DPAR, the BPAQ, and a modified PYPAQ. Peripheral quantitative computed tomography (pQCT) was used to assess bone strength index (BSI) at metaphyseal (4% distal femur and tibia) sites and strength-strain index (SSI) at diaphyseal (femur = 20%, tibia = 66%) sites of the non-dominant leg. Correlations and hierarchical multiple regression were used to assess relationships among PA measures and indices of bone strength. RESULTS After adjustment for maturity, correlations between PA measures and indices of bone strength were positive, although low (r = 0.01–0.20). Regression models that included covariates (maturity, body mass, leg length, and ethnicity) and PA variables showed that PYPAQ score was significantly (P < 0.05) associated with BSI and SSI at all sites and explained more variance in BSI and SSI than any other PA measure. Pedometer steps were significantly (P < 0.05) associated with metaphyseal femur and tibia BSI and 3DPAR score was significantly (P < 0.05) associated with metaphyseal femur BSI. BPAQ score was not significantly (P > 0.05) associated with BSI or SSI at any sites. CONCLUSION A modified PYPAQ that accounts for the duration, frequency, and load of PA predicted indices of bone strength better than other PA measures. PMID:20631644

Subclinical hypervitaminosis A in rat: measurements of bone mineral density (BMD) do not reveal adverse skeletal changes.

PubMed

Lind, P M; Johansson, S; Rönn, M; Melhus, H

2006-01-05

We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet containing 12IU Vitamin A per g pellet (control, C), or a standard diet supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12 weeks. At the end of the study, serum retinyl esters were elevated 4- and 20-fold. Although neither average food intake nor final body weights were significantly different between groups, a dose-dependent reduction in serum levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the length of the humerus was the same as in controls, but the diameter was reduced (-4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the diaphysis showed that bone mineral density (BMD) was unchanged and that periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight of the humerus was not affected, but since bone volume decreased, volumetric BMD, as measured by the bone ash method, even increased (+2.5%, p<0.05). In conclusion, interference with other fat-soluble Vitamins is a possible indirect mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since the WHO criterium for osteoporosis is based on BMD, further studies are warranted to examine whether this is also true in humans.

VITAMIN C AND ZINC INTAKES ARE RELATED TO BONE MACRO-ARCHITECTURAL STRUCTURE AND STRENGTH IN PREPUBESCENT GIRLS

PubMed Central

Laudermilk, Monica J.; Manore, Melinda M.; Thomson, Cynthia A.; Houtkooper, Linda B.; Farr, Joshua N.; Going, Scott B.

2012-01-01

Background The extent to which nutrient intake may influence bone structure and strength during maximum rates of skeletal growth remains uncertain. Objective To examine the relationship of dietary intake of micronutrients and bone macro-architectural structure in young girls. Design This cross-sectional analysis included baseline data from 363 4th and 6th grade girls enrolled in the Jump-In study. Nutrient intake was assessed using the Harvard Youth/Adolescent Food Frequency Questionnaire. Volumetric BMD (vBMD), bone geometry and strength were measured by peripheral quantitative computed tomography (pQCT). Correlations and regression modeling assessed relations between usual nutrient intake and bone parameters. Results In 4th grade girls, metaphyseal and diaphyseal area and circumferences, and diaphyseal strength were associated with vitamin C intake (r = 0.15–0.19; p<0.05). Zinc intake was correlated with diaphyseal vBMD (r = 0.15–0.16; p<0.05). Using multiple linear regression to adjust for important covariates, we observed significant independent associations for vitamin C and zinc with bone parameters. For every mg/d of vitamin C intake trabecular area increased by 11%, cortical strength improved by 14%; and periosteal and endosteal circumferences increased by 5% and 8.6%, respectively. For every mg/d of zinc intake, cortical vBMD increased by <1%. No significant associations were observed in 6th-grade girls. Conclusion Results of this study suggests that vitamin C and zinc intake are positively associated with objective measures of bone geometry, size and strength in 4th-grade girls. This indicates potential differences in micronutrient and bone associations at various age-associated stages of bone maturation perhaps indicative of competing hormonal influences. PMID:23076447

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

PubMed

Sellier, P; Ostertag, A; Collet, C; Trout, H; Champion, K; Fernandez, S; Lopes, A; Morgand, M; Clevenbergh, P; Evans, J; Souak, S; de Vernejoul, M-C; Bergmann, J-F

2016-08-01

HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients. © 2016 British HIV Association.

Better Skeletal Microstructure Confers Greater Mechanical Advantages in Chinese-American Women Versus White Women

PubMed Central

Liu, X Sherry; Walker, Marcella D; McMahon, Donald J; Udesky, Julia; Liu, George; Bilezikian, John P; Guo, X Edward

2013-01-01

Despite lower areal bone mineral density (aBMD), Chinese-American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese-American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image-analysis technique, and micro–finite-element analysis (μFEA) were applied to high-resolution peripheral quantitative computed tomography (HR-pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese-American and white women. Chinese-American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p < .001). With similar rodlike characteristics, the plate-to-rod ratio was twice as high in the Chinese-American than in white trabecular bone (p < .001). Plate-rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese-American women (p < .002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese-American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p < .001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p < .001) and 29% to 43% (distal tibia, p < .01) greater trabecular bone strength, as assessed by Young’s moduli, in the Chinese-American versus the white group. The observation that Chinese-American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD. PMID:21351150

CT reconstruction techniques for improved accuracy of lung CT airway measurement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, A.; Ranallo, F. N.; Judy, P. F.

Purpose: To determine the impact of constrained reconstruction techniques on quantitative CT (qCT) of the lung parenchyma and airways for low x-ray radiation dose. Methods: Measurement of small airways with qCT remains a challenge, especially for low x-ray dose protocols. Images of the COPDGene quality assurance phantom (CTP698, The Phantom Laboratory, Salem, NY) were obtained using a GE discovery CT750 HD scanner for helical scans at x-ray radiation dose-equivalents ranging from 1 to 4.12 mSv (12–100 mA s current–time product). Other parameters were 40 mm collimation, 0.984 pitch, 0.5 s rotation, and 0.625 mm thickness. The phantom was sandwiched betweenmore » 7.5 cm thick water attenuating phantoms for a total length of 20 cm to better simulate the scatter conditions of patient scans. Image data sets were reconstructed using STANDARD (STD), DETAIL, BONE, and EDGE algorithms for filtered back projection (FBP), 100% adaptive statistical iterative reconstruction (ASIR), and Veo reconstructions. Reduced (half) display field of view (DFOV) was used to increase sampling across airway phantom structures. Inner diameter (ID), wall area percent (WA%), and wall thickness (WT) measurements of eight airway mimicking tubes in the phantom, including a 2.5 mm ID (42.6 WA%, 0.4 mm WT), 3 mm ID (49.0 WA%, 0.6 mm WT), and 6 mm ID (49.0 WA%, 1.2 mm WT) were performed with Airway Inspector (Surgical Planning Laboratory, Brigham and Women’s Hospital, Boston, MA) using the phase congruency edge detection method. The average of individual measures at five central slices of the phantom was taken to reduce measurement error. Results: WA% measures were greatly overestimated while IDs were underestimated for the smaller airways, especially for reconstructions at full DFOV (36 cm) using the STD kernel, due to poor sampling and spatial resolution (0.7 mm pixel size). Despite low radiation dose, the ID of the 6 mm ID airway was consistently measured accurately for all methods other than STD FBP. Veo reconstructions showed slight improvement over STD FBP reconstructions (4%–9% increase in accuracy). The most improved ID and WA% measures were for the smaller airways, especially for low dose scans reconstructed at half DFOV (18 cm) with the EDGE algorithm in combination with 100% ASIR to mitigate noise. Using the BONE + ASIR at half BONE technique, measures improved by a factor of 2 over STD FBP even at a quarter of the x-ray dose. Conclusions: The flexibility of ASIR in combination with higher frequency algorithms, such as BONE, provided the greatest accuracy for conventional and low x-ray dose relative to FBP. Veo provided more modest improvement in qCT measures, likely due to its compatibility only with the smoother STD kernel.« less

Polymorphisms in Genes Involved in the NF-κB Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men

PubMed Central

Roshandel, Delnaz; Thomson, Wendy; Pye, Stephen R.; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A.; Bartfai, Gyorgy; Casanueva, Felipe F.; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E.; Pendleton, Neil; Punab, Margus; Wu, Frederick C.

2011-01-01

Introduction In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r2≥0.8) within MAP3K14 (±10 kb) were genotyped in 2359 men aged 40–79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-κB signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health. PMID:22132199

Understanding the reaction between muonium atoms and hydrogen molecules: zero point energy, tunnelling, and vibrational adiabaticity

NASA Astrophysics Data System (ADS)

Aldegunde, J.; Jambrina, P. G.; García, E.; Herrero, V. J.; Sáez-Rábanos, V.; Aoiz, F. J.

2013-11-01

The advent of very precise measurements of rate coefficients in reactions of muonium (Mu), the lightest hydrogen isotope, with H2 in its ground and first vibrational state and of kinetic isotope effects with respect to heavier isotopes has triggered a renewed interests in the field of muonic chemistry. The aim of the present article is to review the most recent results about the dynamics and mechanism of the reaction Mu+H2 to shed light on the importance of quantum effects such as tunnelling, the preservation of the zero point energy, and the vibrational adiabaticity. In addition to accurate quantum mechanical (QM) calculations, quasiclassical trajectories (QCT) have been run in order to check the reliability of this method for this isotopic variant. It has been found that the reaction with H2(v=0) is dominated by the high zero point energy (ZPE) of the products and that tunnelling is largely irrelevant. Accordingly, both QCT calculations that preserve the products' ZPE as well as those based on the Ring Polymer Molecular Dynamics methodology can reproduce the QM rate coefficients. However, when the hydrogen molecule is vibrationally excited, QCT calculations fail completely in the prediction of the huge vibrational enhancement of the reactivity. This failure is attributed to tunnelling, which plays a decisive role breaking the vibrational adiabaticity when v=1. By means of the analysis of the results, it can be concluded that the tunnelling takes place through the ν1=1 collinear barrier. Somehow, the tunnelling that is missing in the Mu+H2(v=0) reaction is found in Mu+H2(v=1).

Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning.

PubMed

Stein, Emily M; Kepley, Anna; Walker, Marcella; Nickolas, Thomas L; Nishiyama, Kyle; Zhou, Bin; Liu, X Sherry; McMahon, Donald J; Zhang, Chiyuan; Boutroy, Stephanie; Cosman, Felicia; Nieves, Jeri; Guo, X Edward; Shane, Elizabeth

2014-01-01

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity.Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius.In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls,despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Hongwei, E-mail: hwsong@wipm.ac.cn; Yang, Minghui; Lu, Yunpeng

An initial state selected time-dependent wave packet method is applied to study the dynamics of the OH + CHD{sub 3} reaction with a six-dimensional model on a newly developed full-dimensional ab initio potential energy surface (PES). This quantum dynamical (QD) study is complemented by full-dimensional quasi-classical trajectory (QCT) calculations on the same PES. The QD results indicate that both translational energy and the excitation of the CH stretching mode significantly promote the reaction while the excitation of the umbrella mode has a negligible effect on the reactivity. For this early barrier reaction, interestingly, the CH stretching mode is more effectivemore » than translational energy in promoting the reaction except at very low collision energies. These QD observations are supported by QCT results. The higher efficacy of the CH stretching model in promoting this early barrier reaction is inconsistent with the prediction of the naively extended Polanyi’s rules, but can be rationalized by the recently proposed sudden vector projection model.« less

Transient chaos - a resolution of breakdown of quantum-classical correspondence in optomechanics.

PubMed

Wang, Guanglei; Lai, Ying-Cheng; Grebogi, Celso

2016-10-17

Recently, the phenomenon of quantum-classical correspondence breakdown was uncovered in optomechanics, where in the classical regime the system exhibits chaos but in the corresponding quantum regime the motion is regular - there appears to be no signature of classical chaos whatsoever in the corresponding quantum system, generating a paradox. We find that transient chaos, besides being a physically meaningful phenomenon by itself, provides a resolution. Using the method of quantum state diffusion to simulate the system dynamics subject to continuous homodyne detection, we uncover transient chaos associated with quantum trajectories. The transient behavior is consistent with chaos in the classical limit, while the long term evolution of the quantum system is regular. Transient chaos thus serves as a bridge for the quantum-classical transition (QCT). Strikingly, as the system transitions from the quantum to the classical regime, the average chaotic transient lifetime increases dramatically (faster than the Ehrenfest time characterizing the QCT for isolated quantum systems). We develop a physical theory to explain the scaling law.

Transient chaos - a resolution of breakdown of quantum-classical correspondence in optomechanics

PubMed Central

Wang, Guanglei; Lai, Ying-Cheng; Grebogi, Celso

2016-01-01

Recently, the phenomenon of quantum-classical correspondence breakdown was uncovered in optomechanics, where in the classical regime the system exhibits chaos but in the corresponding quantum regime the motion is regular - there appears to be no signature of classical chaos whatsoever in the corresponding quantum system, generating a paradox. We find that transient chaos, besides being a physically meaningful phenomenon by itself, provides a resolution. Using the method of quantum state diffusion to simulate the system dynamics subject to continuous homodyne detection, we uncover transient chaos associated with quantum trajectories. The transient behavior is consistent with chaos in the classical limit, while the long term evolution of the quantum system is regular. Transient chaos thus serves as a bridge for the quantum-classical transition (QCT). Strikingly, as the system transitions from the quantum to the classical regime, the average chaotic transient lifetime increases dramatically (faster than the Ehrenfest time characterizing the QCT for isolated quantum systems). We develop a physical theory to explain the scaling law. PMID:27748418

Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

PubMed

Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

2015-07-01

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness-which increased trabecular network heterogeneity-and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Accurate Measurement of Bone Density with QCT

NASA Technical Reports Server (NTRS)

Cleek, Tammy M.; Beaupre, Gary S.; Matsubara, Miki; Whalen, Robert T.; Dalton, Bonnie P. (Technical Monitor)

2002-01-01

The objective of this study was to determine the accuracy of bone density measurement with a new OCT technology. A phantom was fabricated using two materials, a water-equivalent compound and hydroxyapatite (HA), combined in precise proportions (QRM GrnbH, Germany). The phantom was designed to have the approximate physical size and range in bone density as a human calcaneus, with regions of 0, 50, 100, 200, 400, and 800 mg/cc HA. The phantom was scanned at 80, 120 and 140 KVp with a GE CT/i HiSpeed Advantage scanner. A ring of highly attenuating material (polyvinyl chloride or teflon) was slipped over the phantom to alter the image by introducing non-axi-symmetric beam hardening. Images were corrected with a new OCT technology using an estimate of the effective X-ray beam spectrum to eliminate beam hardening artifacts. The algorithm computes the volume fraction of HA and water-equivalent matrix in each voxel. We found excellent agreement between expected and computed HA volume fractions. Results were insensitive to beam hardening ring material, HA concentration, and scan voltage settings. Data from all 3 voltages with a best fit linear regression are displays.

Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

PubMed

Berton, Linda; Bano, Giulia; Carraro, Sara; Veronese, Nicola; Pizzato, Simona; Bolzetta, Francesco; De Rui, Marina; Valmorbida, Elena; De Ronch, Irene; Perissinotto, Egle; Coin, Alessandra; Manzato, Enzo; Sergi, Giuseppe

2015-01-01

Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. ClinicalTrials.gov NCT02118181.

Genetic and environmental determinants of volumetric and areal BMD in multi-generational families of African ancestry: the Tobago Family Health Study.

PubMed

Wang, Xiaojing; Kammerer, Candace M; Wheeler, Victor W; Patrick, Alan L; Bunker, Clareann H; Zmuda, Joseph M

2007-04-01

BMD is higher and fracture risk is lower among individuals of African versus European descent, but little is known about the genetic architecture of BMD in the former group. Heritabilities of areal and volumetric BMD were moderate in our large families of African descent but differed for trabecular and cortical BMD. Populations of African ancestry have lower osteoporotic fracture risk and higher BMD than other ethnic groups. However, there is a paucity of information regarding the genetic and environmental influences on bone health among populations of African heritage. We dissected the genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar spine, and whole body and volumetric BMD measured by pQCT at the distal and proximal radius and tibia in 283 women and 188 men > or =18 years of age (mean, 43 years) from eight multigenerational Afro-Caribbean families (mean family size > 50). Using quantitative genetic methods, we estimated the residual heritability and the effects of anthropometric, demographic, lifestyle, and medical variables on areal and volumetric BMD. Compared with U.S. non-Hispanic blacks and whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and women at all ages. Trabecular volumetric BMD decreased linearly with increasing age, whereas cortical volumetric BMD did not decrease until age 40-49, especially in women. Anthropometric, lifestyle, and medical factors accounted for 12-32% of the variation in areal and volumetric BMD, and residual heritabilities (range, 0.23-0.52) were similar to those reported in other ethnic groups. Heritability of cortical BMD was substantially lower than that of areal or trabecular volumetric BMD, although the measured covariates accounted for a similar proportion of the total phenotypic variation. Our study is the first comprehensive genetic epidemiologic analysis of volumetric BMD measured by QCT and the first analysis of these traits in extended families of African descent. Genes account for as much or more of the total variation in areal and volumetric BMD than do environmental factors, but these effects seem to differ for trabecular and cortical bone.

Study of the variations of fall induced hip fracture risk between right and left femurs using CT-based FEA.

PubMed

Faisal, Tanvir R; Luo, Yunhua

2017-10-03

Hip fracture of elderly people-suffering from osteoporosis-is a severe public health concern, which can be reduced by providing a prior assessment of hip fracture risk. Image-based finite element analysis (FEA) has been considered an effective computational tool to assess the hip fracture risk. Considering the femoral neck region is the weakest, fracture risk indicators (FRI) are evaluated for both single-legged stance and sideways fall configurations and are compared between left and right femurs of each subject. Quantitative Computed Tomography (QCT) scan datasets of thirty anonymous patients' left and right femora have been considered for the FE models, which have been simulated with an equal magnitude of load applied to the aforementioned configurations. The requirement of bilateral hip assessment in predicting the fracture risk has been explored in this study. Comparing the sideways fall and single-legged stance, the FRI varies by 64 to 74% at the superior aspects and by 14 to 19% at the inferior surfaces of both the femora. The results of this in vivo analysis clearly substantiate that the fracture is expected to initiate at the superior surface of femoral neck region if a patient falls from his/her standing height. The distributions of FRI between the femurs vary considerably, and the variability is significant at the superior aspects. The p value (= 0.02) obtained from paired sample t-Test yields p value ≤ 0.05, which shows the evidence of variability of the FRI distribution between left and right femurs. Moreover, the comparison of FRIs between the left and right femur of men and women shows that women are more susceptible to hip fracture than men. The results and statistical variation clearly signify a need for bilateral hip scanning in predicting hip fracture risk, which is clinically conducted, at present, based on one hip chosen randomly and may lead to inaccurate fracture prediction. This study, although preliminary, may play a crucial role in assessing the hip fractures of the geriatric population and thereby, reducing the cost of treatment by taking predictive measure.

Simultaneous determination of mequindox, quinocetone, and their major metabolites in chicken and pork by UPLC-MS/MS

USDA-ARS?s Scientific Manuscript database

This research presents a sensitive and confirmatory multi-residue method for mequindox (MEQ), quinocetone (QCT), and their 11 metabolites in chicken and pork samples. After extracted with acetonitrile-ethyl acetate, acidulated, and extracted again with ethyl acetate sequentially, each sample was pu...

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

NASA Technical Reports Server (NTRS)

Smith, Scott A.; Watts, Nelson; Hans, Didier; LeBlanc, Adrian; Spector, Elisabeth; King, Lisa; Sibonga, Jean

2014-01-01

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 (BMD) and structure result in increased fracture incidence. NASA astronauts currently fly 5 to 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 micro-architecture from lumbar spine (LS). DXA scans are routinely performed pre- and postflight on all ISS astronauts to follow BMD changes associated with spaceflight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from LS 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: Lumbar Spine (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4 yrs) were divided into 3 groups based on the exercise regimens performed onboard the ISS. "Pre-ARED" (exercise using a load-limited resistive exercise device, <300 lb), "ARED" (exercise with a high-load resistive exercise device, up to 600 lb) and "Bisphos+ARED" 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 post-flight scans. LSC for the LS in our laboratory is 0.025 g/sq. cm. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. Data were analyzed using a paired, 2-tailed Student's t-test for the difference between pre- and postflight means. Percent change and % change per month are noted. Interpretation: Our data suggest that: TBS and DXA both detected significant decrements in the LS in these pre- ARED astronauts, not unexpected given the insufficient loads provided by this early exercise device. TBS did not detect significant changes in the ARED or Bisphos+ARED groups while DXA did detect significant changes in the ARED astronauts. These findings suggest that DXA and TBS are detecting independent effects of bone loss interventions tested in ISS astronauts in space, which may be due to distinct effects of interventions on mineral content of separate cortical vs. trabecular bone. Conclusion: TBS, in conjunction with DXA BMD, may provide additional insight into the nature of changes (or lack thereof) in the microstructure of trabecular bone and the areal BMD of vertebral bodies.

Kinetics and dynamics of the C(3P) + H2O reaction on a full-dimensional accurate triplet state potential energy surface.

PubMed

Li, Jun; Xie, Changjian; Guo, Hua

2017-08-30

A full dimensional accurate potential energy surface (PES) for the C( 3 P) and H 2 O reaction is developed based on ∼34 000 data points calculated at the level of the explicitly correlated unrestricted coupled cluster method with single, double, and perturbative triple excitations with the augmented correlation-consistent polarized triple zeta basis set (CCSD(T)-F12a/AVTZ). The PES is invariant with respect to the permutation of the two hydrogen atoms and the total root mean square error (RMSE) of the fit is only 0.31 kcal mol -1 . The PES features two barriers in the entrance channel and several potential minima, as well as multiple product channels. The rate coefficients of this reaction calculated using a transition-state theory and quasi-classical trajectory (QCT) method are small near room temperature, consistent with experiments. The reaction dynamics is also investigated with QCT on the new PES, which found that the reactivity is constrained by the entrance barriers and the final product branching is not statistical.

A comparison of battery testing protocols: Those used by the U.S. advanced battery consortium and those used in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, David C.; Christophersen, Jon P.; Bennett, Taylor

Two testing protocols, QC/T 743 and those used by the U.S. Advanced Battery Consortium (USABC), were compared using cells based on LiFePO4/graphite chemistry. Differences in the protocols directly affected the data and the performance decline mechanisms deduced from the data. In all cases, the rate of capacity fade was linear with time. Overall, the testing protocols produced very similar data when the testing conditions and metrics used to define performance were similar. The choice of depth of discharge and pulse width had a direct effect on the apparent rate of resistance increased and estimated cell life. At greater percent depthmore » of discharge (%DOD) and pulse width, the estimated life was shorter that at lower %DOD and shorter pulse width. This indicates that cells which were at the end of life based on the USABC protocol were not at end of life based on the QC/T 743 protocol by a large margin. (C) 2016 ELSEVIER B.V. All rights reserved.« less

Dynamically biased statistical model for the ortho/para conversion in the H2 + H3+ → H3+ + H2 reaction.

PubMed

Gómez-Carrasco, Susana; González-Sánchez, Lola; Aguado, Alfredo; Sanz-Sanz, Cristina; Zanchet, Alexandre; Roncero, Octavio

2012-09-07

In this work we present a dynamically biased statistical model to describe the evolution of the title reaction from statistical to a more direct mechanism, using quasi-classical trajectories (QCT). The method is based on the one previously proposed by Park and Light [J. Chem. Phys. 126, 044305 (2007)]. A recent global potential energy surface is used here to calculate the capture probabilities, instead of the long-range ion-induced dipole interactions. The dynamical constraints are introduced by considering a scrambling matrix which depends on energy and determine the probability of the identity/hop/exchange mechanisms. These probabilities are calculated using QCT. It is found that the high zero-point energy of the fragments is transferred to the rest of the degrees of freedom, what shortens the lifetime of H(5)(+) complexes and, as a consequence, the exchange mechanism is produced with lower proportion. The zero-point energy (ZPE) is not properly described in quasi-classical trajectory calculations and an approximation is done in which the initial ZPE of the reactants is reduced in QCT calculations to obtain a new ZPE-biased scrambling matrix. This reduction of the ZPE is explained by the need of correcting the pure classical level number of the H(5)(+) complex, as done in classical simulations of unimolecular processes and to get equivalent quantum and classical rate constants using Rice-Ramsperger-Kassel-Marcus theory. This matrix allows to obtain a ratio of hop/exchange mechanisms, α(T), in rather good agreement with recent experimental results by Crabtree et al. [J. Chem. Phys. 134, 194311 (2011)] at room temperature. At lower temperatures, however, the present simulations predict too high ratios because the biased scrambling matrix is not statistical enough. This demonstrates the importance of applying quantum methods to simulate this reaction at the low temperatures of astrophysical interest.

Dynamically biased statistical model for the ortho/para conversion in the H2+H3+ --> H3++ H2 reaction

NASA Astrophysics Data System (ADS)

Gómez-Carrasco, Susana; González-Sánchez, Lola; Aguado, Alfredo; Sanz-Sanz, Cristina; Zanchet, Alexandre; Roncero, Octavio

2012-09-01

In this work we present a dynamically biased statistical model to describe the evolution of the title reaction from statistical to a more direct mechanism, using quasi-classical trajectories (QCT). The method is based on the one previously proposed by Park and Light [J. Chem. Phys. 126, 044305 (2007), 10.1063/1.2430711]. A recent global potential energy surface is used here to calculate the capture probabilities, instead of the long-range ion-induced dipole interactions. The dynamical constraints are introduced by considering a scrambling matrix which depends on energy and determine the probability of the identity/hop/exchange mechanisms. These probabilities are calculated using QCT. It is found that the high zero-point energy of the fragments is transferred to the rest of the degrees of freedom, what shortens the lifetime of H_5^+ complexes and, as a consequence, the exchange mechanism is produced with lower proportion. The zero-point energy (ZPE) is not properly described in quasi-classical trajectory calculations and an approximation is done in which the initial ZPE of the reactants is reduced in QCT calculations to obtain a new ZPE-biased scrambling matrix. This reduction of the ZPE is explained by the need of correcting the pure classical level number of the H_5^+ complex, as done in classical simulations of unimolecular processes and to get equivalent quantum and classical rate constants using Rice-Ramsperger-Kassel-Marcus theory. This matrix allows to obtain a ratio of hop/exchange mechanisms, α(T), in rather good agreement with recent experimental results by Crabtree et al. [J. Chem. Phys. 134, 194311 (2011), 10.1063/1.3587246] at room temperature. At lower temperatures, however, the present simulations predict too high ratios because the biased scrambling matrix is not statistical enough. This demonstrates the importance of applying quantum methods to simulate this reaction at the low temperatures of astrophysical interest.

Social inequalities in osteoporosis and fracture among community-dwelling older men and women: findings from the Hertfordshire Cohort Study.

PubMed

Syddall, Holly E; Evandrou, Maria; Dennison, Elaine M; Cooper, Cyrus; Sayer, Avan Aihie

2012-01-01

It is unknown whether osteoporosis is socially patterned. Using data from the Hertfordshire Cohort Study we found no consistent evidence for social inequalities in prevalent or incident fracture, bone mineral density or loss rates, or bone strength. Public health strategies for prevention of osteoporosis should focus on the whole population. Osteoporosis and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. It is unclear whether osteoporosis and osteoporotic fracture are socially patterned. This study aims to analyse social inequalities in osteoporosis and osteoporotic fracture among the 3,225 community-dwelling men and women, aged 59-73 years, who participated in the Hertfordshire Cohort Study (HCS), UK. A panel of markers of bone health (fracture since 45 years of age; DXA bone mineral density and loss rate at the total femur; pQCT strength strain indices for the radius and tibia; and incident fracture) were analysed in relation to the social circumstances of the HCS participants (characterised at the individual level by: age left full time education; current social class; housing tenure and car availability). We found little strong or consistent evidence among men, or women, for social inequalities in prevalent or incident fracture, DXA bone mineral density, bone loss rates, or pQCT bone strength, with or without adjustment for age, anthropometry, lifestyle and clinical characteristics. Reduced car availability at baseline was associated with lower pQCT radius and tibia strength strain indices at follow-up among men only (p = 0.02 radius and p < 0.01 tibia unadjusted; p = 0.05 radius and p = 0.01 tibia, adjusted for age, anthropometry, lifestyle and clinical characteristics). Our results suggest that fracture and osteoporosis do not have a strong direct social gradient and that public health strategies for prevention and treatment of osteoporosis should continue to focus on the whole population.

Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT.

PubMed

Alomari, Ali Hamed; Wille, Marie-Luise; Langton, Christian M

2018-02-01

Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm -1 ) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS) parameters of velocity and attenuation are dependent upon both bone quantity and bone quality, although it has not been possible to date to transpose one particular QUS parameter into separate estimates of quantity and quality. It has recently been shown that ultrasound transit time spectroscopy (UTTS) may provide an accurate estimate of bone density and hence quantity. We hypothesised that UTTS also has the potential to provide an estimate of bone structure and hence quality. In this in-vitro study, 16 human femoral bone samples were tested utilising three techniques; UTTS, micro computed tomography (μCT), and mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV) and two novel structural parameters, inter-quartile range of the derived transit time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP). μCT was utilised to derive BV/TV along with several bone structure parameters. A destructive mechanical test was utilised to measure the stiffness and strength (failure load) of the bone samples. BV/TV was calculated from the derived transit time spectrum (TTS); the correlation coefficient (R 2 ) with μCT-BV/TV was 0.885. For predicting mechanical stiffness and strength, BV/TV derived by both μCT and UTTS provided the strongest correlation with mechanical stiffness (R 2 =0.567 and 0.618 respectively) and mechanical strength (R 2 =0.747 and 0.736 respectively). When respective structural parameters were incorporated to BV/TV, multiple regression analysis indicated that none of the μCT histomorphometric parameters could improve the prediction of mechanical stiffness and strength, while for UTTS, adding TTMP to BV/TV increased the prediction of mechanical stiffness to R 2 =0.711 and strength to R 2 =0.827. It is therefore envisaged that UTTS may have the ability to estimate BV/TV along with providing an improved prediction of osteoporotic fracture risk, within routine clinical practice in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2

PubMed Central

Nielson, Carrie M; Liu, Ching-Ti; Smith, Albert V; Ackert-Bicknell, Cheryl L; Reppe, Sjur; Jakobsdottir, Johanna; Wassel, Christina; Register, Thomas C; Oei, Ling; Alonso, Nerea; Oei, Edwin H; Parimi, Neeta; Samelson, Elizabeth J; Nalls, Mike A; Zmuda, Joseph; Lang, Thomas; Bouxsein, Mary; Latourelle, Jeanne; Claussnitzer, Melina; Siggeirsdottir, Kristin; Srikanth, Priya; Lorentzen, Erik; Vandenput, Liesbeth; Langefeld, Carl; Raffield, Laura; Terry, Greg; Cox, Amanda J; Allison, Matthew A; Criqui, Michael H; Bowden, Don; Ikram, M Arfan; Mellstrom, Dan; Karlsson, Magnus K; Carr, John; Budoff, Matthew; Phillips, Caroline; Cupples, L Adrienne; Chou, Wen-Chi; Myers, Richard H; Ralston, Stuart H; Gautvik, Kaare M; Cawthon, Peggy M; Cummings, Steven; Karasik, David; Rivadeneira, Fernando; Gudnason, Vilmundur; Orwoll, Eric S; Harris, Tamara B; Ohlsson, Claes; Kiel, Douglas P; Hsu, Yi-Hsiang

2017-01-01

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10−8) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10−10) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10−4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10−3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to linkSLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research. PMID:27476799

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2011-10-11

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Foot-ankle complex injury risk curves using calcaneus bone mineral density data.

PubMed

Yoganandan, Narayan; Chirvi, Sajal; Voo, Liming; DeVogel, Nicholas; Pintar, Frank A; Banerjee, Anjishnu

2017-08-01

Biomechanical data from post mortem human subject (PMHS) experiments are used to derive human injury probability curves and develop injury criteria. This process has been used in previous and current automotive crashworthiness studies, Federal safety standards, and dummy design and development. Human bone strength decreases as the individuals reach their elderly age. Injury risk curves using the primary predictor variable (e.g., force) should therefore account for such strength reduction when the test data are collected from PMHS specimens of different ages (age at the time of death). This demographic variable is meant to be a surrogate for fracture, often representing bone strength as other parameters have not been routinely gathered in previous experiments. However, bone mineral densities (BMD) can be gathered from tested specimens (presented in this manuscript). The objective of this study is to investigate different approaches of accounting for BMD in the development of human injury risk curves. Using simulated underbody blast (UBB) loading experiments conducted with the PMHS lower leg-foot-ankle complexes, a comparison is made between the two methods: treating BMD as a covariate and pre-scaling test data based on BMD. Twelve PMHS lower leg-foot-ankle specimens were subjected to UBB loads. Calcaneus BMD was obtained from quantitative computed tomography (QCT) images. Fracture forces were recorded using a load cell. They were treated as uncensored data in the survival analysis model which used the Weibull distribution in both methods. The width of the normalized confidence interval (NCIS) was obtained using the mean and ± 95% confidence limit curves. The mean peak forces of 3.9kN and 8.6kN were associated with the 5% and 50% probability of injury for the covariate method of deriving the risk curve for the reference age of 45 years. The mean forces of 5.4 kN and 9.2kN were associated with the 5% and 50% probability of injury for the pre-scaled method. The NCIS magnitudes were greater in the covariate-based risk curves (0.52-1.00) than in the risk curves based on the pre-scaled method (0.24-0.66). The pre-scaling method resulted in a generally greater injury force and a tighter injury risk curve confidence interval. Although not directly applicable to the foot-ankle fractures, when compared with the use of spine BMD from QCT scans to pre-scale the force, the calcaneus BMD scaled data produced greater force at the same risk level in general. Pre-scaling the force data using BMD is an alternate, and likely a more accurate, method instead of using covariate to account for the age-related bone strength change in deriving risk curves from biomechanical experiments using PMHS. Because of the proximity of the calcaneus bone to the impacting load, it is suggested to use and determine the BMD of the foot-ankle bone in future UBB and other loading conditions to derive human injury probability curves for the foot-ankle complex. Copyright © 2017. Published by Elsevier Ltd.

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2003-02-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and dual energy X-ray absorptiometry (DXA). The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The following pQCT variables were used: bone mineral content, total cross-sectional area of bone (TotA), cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index for the shaft (BSIt) and compressional bone strength index for the bone end (BSIc). These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater bone mineral content (an average 19% side-to-side difference in young starters and 9% in old starters), was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites), leading to 26% and 11% side-to-side BSIt differences in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' bone mineral content, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' bone mineral content, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side bone mineral content, TrD, and aBMD differences only: the young starters' bone mineral content difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups, the structural adaptation of the humeral shaft to long-term loading seemed to be achieved through periosteal enlargement of the bone cortex, although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends, the trabecular density could be a modifiable factor to built a stronger bone structure. Conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, because it measured two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Greater Polar Moment of Inertia at the Tibia in Athletes Who Develop Stress Fractures

PubMed Central

Weidauer, Lee A.; Binkley, Teresa; Vukovich, Matt; Specker, Bonny

2014-01-01

Background: Several previous investigations have determined potential risk factors for stress fractures in athletes and military personnel. Purpose: To determine factors associated with the development of stress fractures in female athletes. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 88 female athletes (cross-country, n = 29; soccer, n = 15; swimming, n = 9; track and field, n = 14; volleyball, n = 12; and basketball, n = 9) aged 18 to 24 years were recruited to participate in a longitudinal bone study and had their left distal tibia at the 4%, 20%, and 66% sites scanned by peripheral quantitative computed tomography (pQCT). Patients included 23 athletes who developed stress fractures during the following year (cases). Whole body, hip, and spine scans were obtained using dual-energy x-ray absorptiometry (DXA). Analysis of covariance was used to determine differences in bone parameters between cases and controls after adjusting for height, lower leg length, lean mass, fat mass, and sport. Results: No differences were observed between cases and controls in any of the DXA measurements. Cases had significantly greater unadjusted trabecular bone mineral content (BMC), greater polar moment of inertia (PMI) at the 20% site, and greater cortical BMC at the 66% site; however, after adjusting for covariates, the differences became nonsignificant. When analyses were repeated using all individuals who had ever had a stress fracture as cases (n = 31) and after controlling for covariates, periosteal circumference was greater in the cases than the controls (71.1 ± 0.7 vs 69.4 ± 0.5 mm, respectively; P = .04). Conclusion: A history of stress fractures is associated with larger bones. These findings are important because larger bones were previously reported to be protective against fractures and stress fractures, but study findings indicate that may not always be true. One explanation could be that individuals who sustain stress fractures have greater loading that results in greater periosteal circumference but also results in the development of stress fractures. PMID:26535343

Greater Polar Moment of Inertia at the Tibia in Athletes Who Develop Stress Fractures.

PubMed

Weidauer, Lee A; Binkley, Teresa; Vukovich, Matt; Specker, Bonny

2014-07-01

Several previous investigations have determined potential risk factors for stress fractures in athletes and military personnel. To determine factors associated with the development of stress fractures in female athletes. Case-control study; Level of evidence, 3. A total of 88 female athletes (cross-country, n = 29; soccer, n = 15; swimming, n = 9; track and field, n = 14; volleyball, n = 12; and basketball, n = 9) aged 18 to 24 years were recruited to participate in a longitudinal bone study and had their left distal tibia at the 4%, 20%, and 66% sites scanned by peripheral quantitative computed tomography (pQCT). Patients included 23 athletes who developed stress fractures during the following year (cases). Whole body, hip, and spine scans were obtained using dual-energy x-ray absorptiometry (DXA). Analysis of covariance was used to determine differences in bone parameters between cases and controls after adjusting for height, lower leg length, lean mass, fat mass, and sport. No differences were observed between cases and controls in any of the DXA measurements. Cases had significantly greater unadjusted trabecular bone mineral content (BMC), greater polar moment of inertia (PMI) at the 20% site, and greater cortical BMC at the 66% site; however, after adjusting for covariates, the differences became nonsignificant. When analyses were repeated using all individuals who had ever had a stress fracture as cases (n = 31) and after controlling for covariates, periosteal circumference was greater in the cases than the controls (71.1 ± 0.7 vs 69.4 ± 0.5 mm, respectively; P = .04). A history of stress fractures is associated with larger bones. These findings are important because larger bones were previously reported to be protective against fractures and stress fractures, but study findings indicate that may not always be true. One explanation could be that individuals who sustain stress fractures have greater loading that results in greater periosteal circumference but also results in the development of stress fractures.

Effects of administration of four different doses of Escherichia coli phytase on femur properties of 16-week-old turkeys.

PubMed

Tatara, Marcin R; Krupski, Witold; Kozłowski, Krzysztof; Drażbo, Aleksandra; Jankowski, Jan

2015-03-18

The enzyme phytase is able to initiate the release of phosphates from phytic acid, making it available for absorption within gastrointestinal tract and following utilization. The aim of the study was to determine effects of Escherichia coli phytase administration on morphological, densitometric and mechanical properties of femur in 16-week-old turkeys. One-day-old BUT Big-6 males were assigned to six weight-matched groups. Turkeys receiving diet with standard phosphorus (P) and calcium (Ca) content belonged to the positive control group (Group I). Negative control group (Group II) consisted of birds fed diet with lowered P and Ca content. Turkeys belonging to the remaining groups have received the same diet as group II but enriched with graded levels of Escherichia coli phytase: 125 (Group III), 250 (Group IV), 500 (Group V) and 1000 (Group VI) FTU/kg. At the age of 112 days of life, the final body weights were determined and the turkeys were sacrificed to obtain right femur for analyses. Geometric and densitometric properties of femur were determined using quantitative computed tomography (QCT) technique, while mechanical evaluation was performed in three-point bending test. Phytase administration increased cross-sectional area, second moment of inertia, mean relative wall thickness, cortical bone mineral density and maximum elastic strength decreasing cortical bone area of femur (P < 0.05). Reduced dietary Ca and P content decreased final body weight of turkeys by 6.5% (P = 0.006). The most advantageous effects of Escherichia coli phytase administration on geometric, densitometric and mechanical properties of femur were observed in turkeys receiving 125 and 250 FTU/kg of the diet. Phytase administration at the dosages of 500 and 1000 FTU/kg of the diet improved the final body weight in turkeys. The results obtained in this study indicate a possible practical application of Escherichia coli phytase in turkey feeding to improve skeletal system properties and function.

Adaptations in tibial cortical thickness and total volumetric bone density in postmenopausal South Asian women with small bone size.

PubMed

Darling, Andrea L; Hakim, Ohood A; Horton, Khim; Gibbs, Michelle A; Cui, Liang; Berry, Jacqueline L; Lanham-New, Susan A; Hart, Kathryn H

2013-07-01

There is some evidence that South Asian women may have an increased risk of osteoporosis compared with Caucasian women, although whether South Asians are at increased risk of fracture is not clear. It is unknown whether older South Asian women differ from Caucasian women in bone geometry. This is the first study, to the authors' knowledge, to use peripheral Quantitative Computed Tomography (pQCT) to measure radial and tibial bone geometry in postmenopausal South Asian women. In comparison to Caucasian women, Asian women had smaller bone size at the 4% (-18% p<0.001) and 66% radius (-15% p=0.04) as well as increased total density at the 4% (+13% p=0.01) radius. For the tibia, they had a smaller bone size at the 4% (-16% p=0.005) and 14% (-38% p=0.002) sites. Also, Asians had increased cortical thickness (-17% p=0.04) at the 38% tibia, (in proportion to bone size (-30% p=0.003)). Furthermore, at the 4% and 14% tibia there were increased total densities (+12% to +29% p<0.01) and at the 14% tibia there was increased cortical density (+5% p=0.005) in Asians. These differences at the 14% and 38% (but not 4%) remained statistically significant after adjustment for Body Mass Index (BMI). These adaptations are similar to those seen previously in Chinese women. Asian women had reduced strength at the radius and tibia, evidenced by the 20-40% reduction in both polar Strength Strain Index (SSIp) and fracture load (under bending). Overall, the smaller bone size in South Asians is likely to be detrimental to bone strength, despite some adaptations in tibial cortical thickness and tibial and radial density which may partially compensate for this. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of cyclic and impact-based reference point indentation measurements in human cadaveric tibia.

PubMed

Karim, Lamya; Van Vliet, Miranda; Bouxsein, Mary L

2018-01-01

Although low bone mineral density (BMD) is strongly associated with increased fracture risk, up to 50% of those who suffer fractures are not detected as high-risk patients by BMD testing. Thus, new approaches may improve identification of those at increased risk for fracture by in vivo assessment of altered bone tissue properties, which may contribute to skeletal fragility. Recently developed reference point indentation (RPI) allows for assessment of cortical bone indentation properties in vivo using devices that apply cyclic loading or impact loading, but there is little information available to assist with interpretation of RPI measurements. Our goals were to use human cadaveric tibia to determine: 1) the associations between RPI variables, cortical bone density, and morphology; 2) the association between variables obtained from RPI systems using cyclic, slow loading versus a single impact load; and 3) age-related differences in RPI variables. We obtained 20 human tibia and femur pairs from female donors (53-97years), measured total hip BMD using dual-energy X-ray absorptiometry, assessed tibial cortical microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT), and assessed cortical bone indentation properties at the mid-tibial diaphysis using both the cyclic and impact-based RPI systems (Biodent and Osteoprobe, respectively, Active Life Scientific, Santa Barbara, CA). We found a few weak associations between RPI variables, BMD, and cortical geometry; a few weak associations between measurements obtained by the two RPI systems; and no age-related differences in RPI variables. Our findings indicate that in cadaveric tibia from older women RPI measurements are largely independent of age, femoral BMD, and cortical geometry. Furthermore, measurements from the cyclic and impact loading RPI devices are weakly related to each other, indicating that each device reflects different aspects of cortical bone indentation properties. Copyright © 2016. Published by Elsevier Inc.

The Soy Isoflavones to Reduce Bone Loss (SIRBL) Study: Three Year Effects on pQCT Bone Mineral Density and Strength Measures in Postmenopausal Women

USDA-ARS?s Scientific Manuscript database

Soy isoflavones exert inconsistent bone density preserving effects, but the bone strength preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120 mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength ...

Zero-point Energy is Needed in Molecular Dynamics Calculations to Access the Saddle Point for H+HCN→H2CN* and cis/trans-HCNH* on a New Potential Energy Surface.

PubMed

Wang, Xiaohong; Bowman, Joel M

2013-02-12

We calculate the probabilities for the association reactions H+HCN→H2CN* and cis/trans-HCNH*, using quasiclassical trajectory (QCT) and classical trajectory (CT) calculations, on a new global ab initio potential energy surface (PES) for H2CN including the reaction channels. The surface is a linear least-squares fit of roughly 60 000 CCSD(T)-F12b/aug-cc-pVDZ electronic energies, using a permutationally invariant basis with Morse-type variables. The reaction probabilities are obtained at a variety of collision energies and impact parameters. Large differences in the threshold energies in the two types of dynamics calculations are traced to the absence of zero-point energy in the CT calculations. We argue that the QCT threshold energy is the realistic one. In addition, trajectories find a direct pathway to trans-HCNH, even though there is no obvious transition state (TS) for this pathway. Instead the saddle point (SP) for the addition to cis-HCNH is evidently also the TS for direct formation of trans-HCNH.

Reactive Collisions and Final State Analysis in Hypersonic Flight Regime

DTIC Science & Technology

2016-09-13

Kelvin.[7] The gas-phase, surface reactions and energy transfer at these tempera- tures are essentially uncharacterized and the experimental methodologies...high temperatures (1000 to 20000 K) and compared with results from experimentally derived thermodynamics quantities from the NASA CEA (NASA Chemical...with a reproducing kernel Hilbert space (RKHS) method[13] combined with Legendre polynomials; (2) quasi classical trajectory (QCT) calculations to study

77 FR 66902 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... Securities Exchange Act of 1934 (the ``Act'') \\2\\ and Rule 19b-4 thereunder,\\3\\ notice is hereby given that... least 1,000 contracts, is part of a QCT, and is executed at a price at least equal to the national best... per contract than they would pay if the trade were executed as a non-QCC trade. Currently...

Update of Bisphosphonate Flight Experiment

NASA Technical Reports Server (NTRS)

LeBlanc, A.; Matsumoto, T.; Jones, J.; Shapiro, J.; Lang, T.; Shackelford, L.; Smith, S. M.; Evans, H.; Spector, E.; Snyder, R. P.;

Bone Mineral 31P and Matrix-Bound Water Densities Measured by Solid-State 1H and 31P MRI

PubMed Central

Seifert, Alan C.; Li, Cheng; Rajapakse, Chamith S.; Bashoor- Zadeh, Mahdieh; Bhagat, Yusuf A.; Wright, Alexander C.; Zemel, Babette S.; Zavaliangos, Antonios; Wehrli, Felix W.

2014-01-01

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging due to extremely short transverse relaxation times, but solid-state imaging sequences exist that can acquire the short-lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI-based measurement on clinical scanners of bone mineral and collagen-bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors’ age. Mineral and matrix-bound water images of reference phantoms and cortical bone from 16 human donors, ages 27-97 years, were acquired by zero-echo-time 31P and 1H MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro-CT, and apparent mineral density by pQCT. MRI-derived densities were compared to x-ray-based measurements by least-squares regression. Mean bone mineral 31P density was 6.74±1.22 mol/L (corresponding to 1129±204 mg/cc mineral), and mean bound water 1H density was 31.3±4.2 mol/L (corresponding to 28.3±3.7 %v/v). Both 31P and bound water (BW) densities were correlated negatively with porosity (31P: R2 = 0.32, p < 0.005; BW: R2 = 0.63, p < 0.0005) and age (31P: R2 = 0.39, p < 0.05; BW: R2 = 0.70, p < 0.0001), and positively with pQCT density (31P: R2 = 0.46, p < 0.05; BW: R2 = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of 31P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age, or pQCT density. This work establishes the feasibility of image-based quantification of bone mineral and bound water densities using clinical hardware. PMID:24846186

Vibrations of a Marine Propeller Operating in a Nonuniform Inflow.

DTIC Science & Technology

1980-04-01

Expanded Blade Midsurface ......... ........................ ... 73 16 - Calculated Normalized Propeller RMS Vibration Velocity as a Function of...averaged over the blade midsurface ), rather thaft the maximum velocities near the blade tip. Then, for the two test propellers, the rms nonuniform inflow...time- averaged midsurface of the blade, then the instantaneous position S of the vibrating midsurface is _S (ric)+ qct S(r,c,t) = (rc) + q(t) i(rc

Comparison of DSMC Reaction Models with QCT Reaction Rates for Nitrogen

DTIC Science & Technology

2016-07-17

The U.S. Government is joint author of the work and has the right to use, modify, reproduce, release, perform, display, or disclose the work. 13...Distribution A: Approved for Public Release, Distribution Unlimited PA #16299 Introduction • Comparison with measurements is final goal • Validation...model verification and parameter adjustment • Four chemistry models: total collision energy (TCE), quantum kinetic (QK), vibration-dissociation favoring

Assessment of Hip Fracture Risk Using Cross-Section Strain Energy Determined by QCT-Based Finite Element Modeling

PubMed Central

Kheirollahi, Hossein

2015-01-01

Accurate assessment of hip fracture risk is very important to prevent hip fracture and to monitor the effect of a treatment. A subject-specific QCT-based finite element model was constructed to assess hip fracture risk at the critical locations of femur during the single-leg stance and the sideways fall. The aim of this study was to improve the prediction of hip fracture risk by introducing a novel failure criterion to more accurately describe bone failure mechanism. Hip fracture risk index was defined using cross-section strain energy, which is able to integrate information of stresses, strains, and material properties affecting bone failure. It was found that the femoral neck and the intertrochanteric region have higher fracture risk than other parts of the femur, probably owing to the larger content of cancellous bone in these regions. The study results also suggested that women are more prone to hip fracture than men. The findings in this study have a good agreement with those clinical observations reported in the literature. The proposed hip fracture risk index based on strain energy has the potential of more accurate assessment of hip fracture risk. However, experimental validation should be conducted before its clinical applications. PMID:26601105

Development of a novel method for surgical implant design optimization through noninvasive assessment of local bone properties.

PubMed

Schiuma, D; Brianza, S; Tami, A E

2011-03-01

A method was developed to improve the design of locking implants by finding the optimal paths for the anchoring elements, based on a high resolution pQCT assessment of local bone mineral density (BMD) distribution and bone micro-architecture (BMA). The method consists of three steps: (1) partial fixation of the implant to the bone and creation of a reference system, (2) implant removal and pQCT scan of the bone, and (3) determination of BMD and BMA of all implant-anchoring locations along the actual and alternative directions. Using a PHILOS plate, the method uncertainty was tested on an artificial humerus bone model. A cadaveric humerus was used to quantify how the uncertainty of the method affects the assessment of bone parameters. BMD and BMA were determined along four possible alternative screw paths as possible criteria for implant optimization. The method is biased by a 0.87 ± 0.12 mm systematic uncertainty and by a 0.44 ± 0.09 mm random uncertainty in locating the virtual screw position. This study shows that this method can be used to find alternative directions for the anchoring elements, which may possess better bone properties. This modification will thus produce an optimized implant design. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Internal energy of HCl upon photolysis of 2-chloropropene at 193 nm investigated with time-resolved Fourier-transform spectroscopy and quasiclassical trajectories

NASA Astrophysics Data System (ADS)

Chang, Chih-Min; Huang, Yu-Hsuan; Liu, Suet-Yi; Lee, Yuan-Pern; Pombar-Pérez, Marta; Martínez-Núñez, Emilio; Vázquez, Saulo A.

2008-12-01

Following photodissociation of 2-chloropropene (H2CCClCH3) at 193 nm, vibration-rotationally resolved emission spectra of HCl (υ ≤6) in the spectral region of 1900-2900 cm-1 were recorded with a step-scan time-resolved Fourier-transform spectrometer. All vibrational levels show a small low-J component corresponding to ˜400 K and a major high-J component corresponding to 7100-18 700 K with average rotational energy of 39±311 kJ mol-1. The vibrational population of HCl is inverted at υ =2, and the average vibrational energy is 86±5 kJ mol-1. Two possible channels of molecular elimination producing HCl+propyne or HCl+allene cannot be distinguished positively based on the observed internal energy distribution of HCl. The observed rotational distributions fit qualitatively with the distributions of both channels obtained with quasiclassical trajectories (QCTs), but the QCT calculations predict negligible populations for states at small J. The observed vibrational distribution agrees satisfactorily with the total QCT distribution obtained as a weighted sum of contributions from both four-center elimination channels. Internal energy distributions of HCl from 2-chloropropene and vinyl chloride are compared.

Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

PubMed

Felice, Juan Ignacio; Schurman, León; McCarthy, Antonio Desmond; Sedlinsky, Claudia; Aguirre, José Ignacio; Cortizo, Ana María

2017-04-01

Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture. 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential. Metformin improved blood parameters in FRDM rats. pQCT and static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters. FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Feiveson, A. H.

2014-01-01

This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an applicant for astronaut candidacy, b) Qualify an astronaut for a long-duration (LD) mission, c) Qualify a veteran LD astronaut for a second LD mission, and d) Establish a non-permissible, minimum hip strength following a given mission architecture. This abstract will present the FE-based standards accepted by the FE Strength Task Group for its recommendation to HHC in January 2015.

Pulmonary Function Testing in Aviation Selectees,

DTIC Science & Technology

1976-05-17

Co0 C\\j C’%j 4co co~* 04 00 EL 43 CD X0 Z4- (Dco r-.. Eu 01~. 4J w .co %0co 0i co i.- Va) ta.o CCto IL. C14-~ qct(W 00 ~C* 4p) (3UW L- S-4*.- U) *4-J4J 434J 43cLALLLA- C 4) " U U M C U- LA- W M V)’

Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone

DTIC Science & Technology

2015-10-01

JJPVAMC). During year 1 of the study, the Study Team (Drs. Forrest, Bauman, and Harkema) established a new partnership with a pharmaceutical company...AbbVie) to supply Drug and Placebo for all potential study participants. Each of the study sites submitted to the pharmaceutical company all requested...stimulation, dynamic standing protocol, muscle volume, MRI , bone mineral density, DXA, QCT scans, blood markers, urine markers, 60 sessions of training

Risk Stratification of Stress Fractures and Prediction of Return to Duty

DTIC Science & Technology

2015-12-01

enrollment. In study Task 1 we aim to determine the sex- and race -ethnicity-specific bone traits that may contribute to stress fracture risk in military...SUBJECT TERMS bone microarchitecture, HRpQCT, race , gender, sex, bone mineral density, vBMD, bone geometry, stress fracture 16. SECURITY...sectional study aimed at identifying the bone properties that may be related to the well-known sex and race /ethnicity differences in risk for stress

Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women.

PubMed

Popp, Kristin L; Hughes, Julie M; Martinez-Betancourt, Adriana; Scott, Matthew; Turkington, Victoria; Caksa, Signe; Guerriere, Katelyn I; Ackerman, Kathryn E; Xu, Chun; Unnikrishnan, Ginu; Reifman, Jaques; Bouxsein, Mary L

2017-10-01

Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure. We determined differences in bone mass, microarchitecture and strength between young adult Black and White men and women. We enrolled 185 young adult (24.2±3.4yrs) women (n=51 Black, n=50 White) and men (n=34 Black, n=50 White) in this cross-sectional study. We used dual-energy X-ray absorptiometry (DXA) to determine areal BMD (aBMD) at the femoral neck (FN), total hip (TH) and lumbar spine (LS), as well as HR-pQCT to assess bone microarchitecture and failure load by micro-finite element analysis (μFEA) at the distal tibia (4% of tibial length). We used two-way ANOVA to compare bone outcomes, adjusted for age, height, weight and physical activity. The effect of race/ethnicity on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race/ethnicty. After adjusting for covariates, Blacks had significantly greater FN, TH and LS aBMD compared to Whites (p<0.05 for all). Blacks also had greater cortical area, vBMD, and thickness, and lower cortical porosity, with greater trabecular thickness and total vBMD compared to Whites. μFEA-estimated FL was significantly higher among Blacks compared to Whites. Men had significantly greater total vBMD, trabecular thickness and cortical area and thickness, but greater cortical porosity than women, the net effects being a higher failure load in men than women. These findings demonstrate that more favorable bone microarchitecture in Blacks compared to Whites and in men compared to women is established by young adulthood. Advantageous bone strength among Blacks and men likely contributes to their lower risk of fractures throughout life compared to their White and women counterparts. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of a single trajectory to study product energy partitioning in unimolecular dissociation: mass effects for halogenated alkanes.

PubMed

Sun, Lipeng; Park, Kyoyeon; Song, Kihyung; Setser, Donald W; Hase, William L

2006-02-14

A single trajectory (ST) direct dynamics approach is compared with quasiclassical trajectory (QCT) direct dynamics calculations for determining product energy partitioning in unimolecular dissociation. Three comparisons are made by simulating C(2)H(5)F-->HF + C(2)H(4) product energy partitioning for the MP26-31G(*) and MP26-311 + + G(**) potential energy surfaces (PESs) and using the MP26-31G(*) PES for C(2)H(5)F dissociation as a model to simulate CHCl(2)CCl(3)-->HCl + C(2)Cl(4) dissociation and its product energy partitioning. The trajectories are initiated at the transition state with fixed energy in reaction-coordinate translation E(t) (double dagger). The QCT simulations have zero-point energy (ZPE) in the vibrational modes orthogonal to the reaction coordinate, while there is no ZPE for the STs. A semiquantitative agreement is obtained between the ST and QCT average percent product energy partitionings. The ST approach is used to study mass effects for product energy partitioning in HX(X = F or Cl) elimination from halogenated alkanes by using the MP26-31G(*) PES for C(2)H(5)F dissociation and varying the masses of the C, H, and F atoms. There is, at most, only a small mass effect for partitioning of energy to HX vibration and rotation. In contrast, there are substantial mass effects for partitioning to relative translation and the polyatomic product's vibration and rotation. If the center of mass of the polyatomic product is located away from the C atom from which HX recoils, the polyatomic has substantial rotation energy. Polyatomic products, with heavy atoms such as Cl atoms replacing the H atoms, receive substantial vibration energy that is primarily transferred to the wag-bend motions. For E(t) (double dagger) of 1.0 kcalmol, the ST calculations give average percent partitionings to relative translation, polyatomic vibration, polyatomic rotation, HX vibration, and HX rotation of 74.9%, 6.8%, 1.5%, 14.4%, and 2.4% for C(2)H(5)F dissociation and 39.7%, 38.1%, 0.2%, 16.1%, and 5.9% for a model of CHCl(2)CCl(3) dissociation.

Study of the formation of interstellar CF+ from the HF + C + →CF+ + H reaction

NASA Astrophysics Data System (ADS)

Denis-Alpizar, Otoniel; Guzmán, Viviana V.; Inostroza, Natalia

2018-06-01

The detection of the carbon monofluoride cation CF+ was considered as a support of the theories of the fluorine chemistry in the interstellar medium (ISM). This molecule is formed by the reaction of HF with C+. The rates of this reaction have been estimated previously by two different groups. However, these two estimations led to different results. The main goal of the present work is to study the HF + C+ reaction and determine new reactive rate coefficients. A large set of ab initio energies at the MRCI-F12/cc-pVQZ-F12 level was computed. The first reactive potential energy surface (PES) for the HF + C+ → CF+ + H reaction was developed using a reproducing kernel Hilbert space (RKHS) based method. The dynamics of the reaction was followed from quasiclassical trajectories (QCT). The results of such calculations showed that CF+ is produced in excited vibrational states. The rate coefficients for the HF + C+ → CF+ + H reaction from 50 K up to 2000 K are reported. The impact of these new data in the astrophysical models for the determination of the interstellar conditions is also explored.

QSAR models based on quantum topological molecular similarity.

PubMed

Popelier, P L A; Smith, P J

2006-07-01

A new method called quantum topological molecular similarity (QTMS) was fairly recently proposed [J. Chem. Inf. Comp. Sc., 41, 2001, 764] to construct a variety of medicinal, ecological and physical organic QSAR/QSPRs. QTMS method uses quantum chemical topology (QCT) to define electronic descriptors drawn from modern ab initio wave functions of geometry-optimised molecules. It was shown that the current abundance of computing power can be utilised to inject realistic descriptors into QSAR/QSPRs. In this article we study seven datasets of medicinal interest : the dissociation constants (pK(a)) for a set of substituted imidazolines , the pK(a) of imidazoles , the ability of a set of indole derivatives to displace [(3)H] flunitrazepam from binding to bovine cortical membranes , the influenza inhibition constants for a set of benzimidazoles , the interaction constants for a set of amides and the enzyme liver alcohol dehydrogenase , the natriuretic activity of sulphonamide carbonic anhydrase inhibitors and the toxicity of a series of benzyl alcohols. A partial least square analysis in conjunction with a genetic algorithm delivered excellent models. They are also able to highlight the active site, of the ligand or the molecule whose structure determines the activity. The advantages and limitations of QTMS are discussed.

Development of a two-dimensional binning model for N{sub 2}–N relaxation in hypersonic shock conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Tong, E-mail: tongzhu2@illinois.edu; Levin, Deborah A., E-mail: deblevin@illinois.edu; Li, Zheng, E-mail: zul107@psu.edu

2016-08-14

A high fidelity internal energy relaxation model for N{sub 2}–N suitable for use in direct simulation Monte Carlo (DSMC) modeling of chemically reacting flows is proposed. A novel two-dimensional binning approach with variable bin energy resolutions in the rotational and vibrational modes is developed for treating the internal mode of N{sub 2}. Both bin-to-bin and state-specific relaxation cross sections are obtained using the molecular dynamics/quasi-classical trajectory (MD/QCT) method with two potential energy surfaces as well as the state-specific database of Jaffe et al. The MD/QCT simulations of inelastic energy exchange between N{sub 2} and N show that there is amore » strong forward-preferential scattering behavior at high collision velocities. The 99 bin model is used in homogeneous DSMC relaxation simulations and is found to be able to recover the state-specific master equation results of Panesi et al. when the Jaffe state-specific cross sections are used. Rotational relaxation energy profiles and relaxation times obtained using the ReaxFF and Jaffe potential energy surfaces (PESs) are in general agreement but there are larger differences between the vibrational relaxation times. These differences become smaller as the translational temperature increases because the difference in the PES energy barrier becomes less important.« less

Comparison of pQCT parameters between ulna and radius in retired elite gymnasts: the skeletal benefits associated with long-term gymnastics are bone- and site-specific.

PubMed

Ducher, G; Hill, B L; Angeli, T; Bass, S L; Eser, P

2009-01-01

To compare the skeletal benefits associated with gymnastics between ulna and radius. 19 retired artistic gymnasts, aged 18-36 years, were compared to 24 sedentary women. Bone mineral content (BMC), total and cortical bone area (ToA, CoA), trabecular and cortical volumetric density (TrD, CoD) and cortical thickness (CoTh) were measured by pQCT at the 4% and 66% forearm. At the 4% site, BMC and ToA were more than twice greater at the radius than ulna whereas at the 66% site, BMC, ToA, CoA, CoTh and SSIpol were 20 to 51% greater at the ulna than radius in both groups (p<0.0001). At the 4% site, the skeletal benefits in BMC of the retired gymnasts over the non-gymnasts were 1.9 times greater at the radius than ulna (p<0.001), with enlarged bone size at the distal radius only. In contrast, the skeletal benefits at the 66% site were twice greater at the ulna than radius for BMC and CoA (p<0.01). Whereas the skeletal benefits associated with long-term gymnastics were greater at the radius than ulna in the distal forearm, the reverse was found in the proximal forearm, suggesting both bones should be analysed when investigating forearm strength.

In healthy elderly postmenopausal women variations in BMD and BMC at various skeletal sites are associated with differences in weight and lean body mass rather than by variations in habitual physical activity, strength or VO2max.

PubMed

Schöffl, I; Kemmler, W; Kladny, B; Vonstengel, S; Kalender, W A; Engelke, K

2008-01-01

The objective of this study was an integrated cross-sectional investigation for answering the question whether differences in bone mineral density in elderly postmenopausal women are associated with differences in habitual physical activity and unspecific exercise levels. Two hundred and ninety nine elderly women (69-/+3 years), without diseases or medication affecting bone metabolism were investigated. The influence of weight, body composition and physical activity on BMD was measured at multiple sites using different techniques (DXA, QCT, and QUS). Physical activity and exercise level were assessed by questionnaire, maximum strength of the legs and aerobic capacity. Variations in physical activity or habitual exercise had no effect on bone. The only significant univariate relation between strength/VO(2)max and BMD/BMC that remained after adjusting for confounding variables was between arm BMD (DXA) and hand-grip strength. The most important variable for explaining BMD was weight and for cortical BMC of the femur (QCT) lean body mass. Weight and lean body mass emerge as predominant predictors of BMD in normal elderly women, whereas the isolated effect of habitual physical activity, unspecific exercise participation, and muscle strength on bone parameters is negligible. Thus, an increase in the amount of habitual physical activity will probably have no beneficial impact on bone.

Bone healing and mineralization, implant corrosion, and trace metals after nickel-titanium shape memory metal intramedullary fixation.

PubMed

Ryhänen, J; Kallioinen, M; Serlo, W; Perämäki, P; Junila, J; Sandvik, P; Niemelä, E; Tuukkanen, J

1999-12-15

Its shape memory effect, superelasticity, and good wear and damping properties make the NiTi shape memory alloy a material with fascinating potential for orthopedic surgery. It provides a possibility for making self-locking, self-expanding, and self-compressing implants. Problems, however, may arise because of its high nickel content. The purpose of this work was to determine the corrosion of NiTi in vivo and to evaluate the possible deleterious effects of NiTi on osteotomy healing, bone mineralization, and the remodeling response. Femoral osteotomies of 40 rats were fixed with either NiTi or stainless steel (StSt) intramedullary nails. The rats were killed at 2, 4, 8, 12, 26, and 60 weeks. Bone healing was examined with radiographs, peripheral quantitative computed tomography, (pQCT) and histologically. The corrosion of the retrieved implants was analyzed by electron microscopy (FESEM). Trace metals from several organs were determined by graphite furnace atomic absorption spectrometry (GF-AAS) or by inductively coupled plasma-atomic emission spectrometry (ICP-AES). There were more healed bone unions in the NiTi than in the StSt group at early (4 and 8 weeks) time points. Callus size was equal between the groups. The total and cortical bone mineral densities did not differ between the NiTi and StSt groups. Mineral density in both groups was lower in the osteotomy area than in the other areas along the nail. Density in the nail area was lower than in the proximal part of the operated femur or the contralateral femur. Bone contact to NiTi was close. A peri-implant lamellar bone sheet formed in the metaphyseal area after 8 weeks, indicating good tissue tolerance. The FESEM assessment showed surface corrosion changes to be more evident in the StSt implants. There were no statistically significant differences in nickel concentration between the NiTi and StSt groups in any of the organs. NiTi appears to be an appropriate material for further intramedullary use because it has good biocompatibility in bone tissue. Copyright 1999 John Wiley & Sons, Inc.

Effect of Denosumab on Peripheral Compartmental Bone Density, Microarchitecture and Estimated Bone Strength in De Novo Kidney Transplant Recipients.

PubMed

Bonani, Marco; Meyer, Ursina; Frey, Diana; Graf, Nicole; Bischoff-Ferrari, Heike A; Wüthrich, Rudolf P

2016-01-01

In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14). Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336). These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis. © 2016 The Author(s) Published by S. Karger AG, Basel.

The effect of oral ipriflavone on the rat mandible during growth.

PubMed

Maki, Kenshi; Nishida, Ikuko; Kimura, Mitsutaka

2005-02-01

Different types of ipriflavone (IF) have been reported to be effective when used as a remedy for bone loss due to osteoporosis. However, no information is available regarding the relationship between IF and jaw bone structure. The aim of this study was to examine the effect of IF on rat mandibles during the growth stage. Thirty-two 5-week-old Wistar male rats were divided into four groups. The control group was fed a standard diet, group A received a low calcium diet (calcium content 30 per cent of the standard diet) for 6 weeks, and the other two groups were fed a low calcium diet for 3 weeks and then a standard diet without IF (group B) or with IF (group C) for 3 weeks. In addition, distilled water was provided for all groups. The effects of IF on mandibular size and bone mineral content were investigated, using lateral cephalometric analysis and peripheral quantitative computed tomography (pQCT). For mandibular length, the control group showed a significantly higher value than groups A and B (P < 0.01, P < 0.05, respectively), while group C demonstrated a significantly higher value than group A (P < 0.01). In addition, the control group and group C showed significantly higher values for mandibular ramus height than group A (P < 0.01). However, bone mineral density in trabecular bone was significantly higher in the control group than in the other groups (P < 0.01) and bone mineral density in cortical bone was significantly higher in the control group than groups A, B and C (P < 0.01, P < 0.01, P < 0.05, respectively). Bone mineral density in both trabecular and cortical bone was significantly higher in group C than in groups A and B (P < 0.01, P < 0.05, respectively). These results indicate that complete recovery from calcium deficiency to the level of the control group may not be attainable, even though IF enhances calcium absorption to act on bone cells and promote bone construction. The importance of calcium intake in the early stages of development was confirmed. These findings also suggest an effect of IF on jaw bone structure.

Areal and volumetric bone mineral density and risk of multiple types of fracture in older men.

PubMed

Chalhoub, Didier; Orwoll, Eric S; Cawthon, Peggy M; Ensrud, Kristine E; Boudreau, Robert; Greenspan, Susan; Newman, Anne B; Zmuda, Joseph; Bauer, Douglas; Cummings, Steven; Cauley, Jane A

2016-11-01

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7years of follow-up. Men answered questionnaires about fractures every 4months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24-3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. Copyright © 2016 Elsevier Inc. All rights reserved.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

PubMed

Laurent, M R; Cook, M J; Gielen, E; Ward, K A; Antonio, L; Adams, J E; Decallonne, B; Bartfai, G; Casanueva, F F; Forti, G; Giwercman, A; Huhtaniemi, I T; Kula, K; Lean, M E J; Lee, D M; Pendleton, N; Punab, M; Claessens, F; Wu, F C W; Vanderschueren, D; Pye, S R; O'Neill, T W

2016-11-01

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density ( a BMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine a BMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip a BMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models. Men with MetS have higher a BMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

Longitudinal relationships between whole body and central adiposity on weight-bearing bone geometry, density, and bone strength: a pQCT study in young girls

PubMed Central

Farr, Joshua N.; Laudermilk, Monica J.; Lee, Vinson R.; Blew, Robert M.; Stump, Craig; Houtkooper, Linda; Lohman, Timothy G.; Going, Scott B.

2015-01-01

Summary Longitudinal relationships between adiposity (total body and central) and bone development were assessed in young girls. Total body and android fat masses were positively associated with bone strength and density parameters of the femur and tibia. These results suggest adiposity may have site-specific stimulating effects on the developing bone. Introduction Childhood obesity may impair bone development, but the relationships between adiposity and bone remain unclear. Failure to account for fat pattern may explain the conflicting results. Purpose Longitudinal associations of total body fat mass (TBFM) and android fat mass (AFM) with 2-year changes in weight-bearing bone parameters were examined in 260 girls aged 8–13 years at baseline. Peripheral quantitative computed tomography was used to measure bone strength index (BSI, square milligrams per quartic millimeter), strength–strain index (SSI, cubic millimeters), and volumetric bone mineral density (vBMD, milligrams per cubic centimeter) at distal metaphyseal and diaphyseal regions of the femur and tibia. TBFM and AFM were assessed by dual-energy x-ray absorptiometry. Results Baseline TBFM and AFM were positively associated with the change in femur BSI (r =0.20, r =0.17, respectively) and femur trabecular vBMD (r =0.19, r =0.19, respectively). Similarly, positive associations were found between TBFM and change in tibia BSI and SSI (r =0.16, r =0.15, respectively), and femur total and trabecular vBMD (r =0.12, r =0.14, respectively). Analysis of covariance showed that girls in the middle thirds of AFM had significantly lower femur trabecular vBMD and significantly higher tibia cortical vBMD than girls in the highest thirds of AFM. All results were significant at p <0.05. Conclusions Whereas baseline levels of TBFM and AFM are positive predictors of bone strength and density at the femur and tibia, higher levels of AFM above a certain level may impair cortical vBMD growth at weight-bearing sites. Future studies in obese children will be needed to test this possibility. NIH/NICHD #HD-050775. PMID:24113839

A longitudinal study of bone area, content, density, and strength development at the radius and tibia in children 4-12 years of age exposed to recreational gymnastics.

PubMed

Jackowski, S A; Baxter-Jones, A D G; Gruodyte-Raciene, R; Kontulainen, S A; Erlandson, M C

2015-06-01

This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm(2)) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius (p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia (p > 0.05). Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist.

Areal and volumetric Bone Mineral Density and risk of multiple types of fracture in older men

PubMed Central

Chalhoub, Didier; Orwoll, Eric S.; Cawthon, Peggy M.; Ensrud, Kristine E.; Boudreau, Robert; Greenspan, Susan; Newman, Anne B.; Zmuda, Joseph; Bauer, Douglas; Cummings, Steven; Cauley, Jane A.

2016-01-01

Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7 years of follow up. Men answered questionnaires about fractures every 4 months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24 - 3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater metabolic activity of the trabecular compartment. PMID:27554426

A two-year program of aerobics and weight training enhances bone mineral density of young women.

PubMed

Friedlander, A L; Genant, H K; Sadowsky, S; Byl, N N; Glüer, C C

1995-04-01

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

Long-term changes in the density and structure of the human hip and spine after long-duration spaceflight

NASA Astrophysics Data System (ADS)

Dana Carpenter, R.; LeBlanc, Adrian D.; Evans, Harlan; Sibonga, Jean D.; Lang, Thomas F.

2010-07-01

To determine the long-term effects of long-duration spaceflight, we measured bone mineral density and bone geometry of International Space Station (ISS) crewmembers using quantitative computed tomography (QCT) before launch, immediately upon their return, one year after return, and 2-4.5 years after return from the ISS. Eight crew members (7 male, 1 female, mean age 45±4 years at start of mission) who spent an average of 181 days (range 161-196 days) aboard the ISS took part in the study. Integral bone mineral density (iBMD), trabecular BMD (tBMD), bone mineral content (BMC), and vertebral cross-sectional area (CSA) were measured in the lumbar spine, and iBMD, tBMD, cortical BMD (cBMD), BMC, CSA, volume, and femoral neck section modulus were measured in the hip. Spine iBMD was 95% of the average preflight value upon return from the ISS and reached its preflight value over the next 2-4.5 years. Spine tBMD was 97% of the average preflight value upon return from the ISS and tended to decrease throughout the course of the study. Vertebral CSA remained essentially unchanged throughout the study. Hip iBMD was 91% of the preflight value upon return from the ISS and was 95% of the preflight value after 2-4.5 years of recovery. Hip tBMD was 88% of the preflight value upon return and recovered to only 93% of the preflight value after 1 year. At the 2- to 4.5-year time point, average tBMD was 88% of the preflight value. During the recovery period the total volume and cortical bone volume in the hip reached values of 114% and 110% of their preflight values, respectively. The combination of age-related bone loss, long-duration spaceflight, and re-adaptation to the 1-g terrestrial environment presumably produced these changes. These long-term data suggest that skeletal changes that occur during long-duration spaceflight persist even after multiple years of recovery. These changes have important implications for the skeletal health of crew members, especially those who make repeat trips to space.

Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes.

PubMed

Lenchik, L; Register, T C; Russell, G B; Xu, J; Smith, S C; Bowden, D W; Divers, J; Freedman, B I

2018-05-31

The study showed that in African-American men with type 2 diabetes mellitus (T2D), vertebral volumetric bone mineral density (vBMD) predicts all-cause mortality, independent of other risk factors for death. Compared to European Americans, African Americans have lower rates of osteoporosis and higher rates of T2D. The relationships between BMD and fractures with mortality are unknown in this population. The aim of this study was to determine relationships between vertebral fractures and vertebral vBMD and mortality in African Americans with T2D. Associations between vertebral fractures and vBMD with all-cause mortality were examined in 675 participants with T2D (391 women and 284 men) in the African American-Diabetes Heart Study (AA-DHS). Lumbar and thoracic vBMD were measured using quantitative computed tomography (QCT). Vertebral fractures were assessed on sagittal CT images. Associations of vertebral fractures and vBMD with all-cause mortality were determined in sex-stratified analyses and in the full sample. Covariates in a minimally adjusted model included age, sex, BMI, smoking, and alcohol use; the full model was adjusted for those variables plus cardiovascular disease, hypertension, coronary artery calcified plaque, hormone replacement therapy (women), African ancestry proportion, and eGFR. After mean 7.6 ± 1.8-year follow-up, 59 (15.1%) of women and 58 (20.4%) of men died. In men, vBMD was inversely associated with mortality in the fully adjusted model: lumbar hazard ratio (HR) per standard deviation (SD) = 0.70 (95% CI 0.52-0.95, p = 0.02) and thoracic HR per SD = 0.71 (95% CI 0.54-0.92, p = 0.01). Only trends toward association between vBMD and mortality were observed in the combined sample of men and women, as significant associations were absent in women. Vertebral fractures were not associated with mortality in either sex. Lower vBMD was associated with increased all-cause mortality in African-American men with T2D, independent of other risk factors for mortality including subclinical atherosclerosis.

A two-year program of aerobics and weight training enhances bone mineral density of young women

NASA Technical Reports Server (NTRS)

Friedlander, A. L.; Genant, H. K.; Sadowsky, S.; Byl, N. N.; Gluer, C. C.

1995-01-01

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

Deficits in distal radius bone strength, density and microstructure are associated with forearm fractures in girls: an HR-pQCTstudy

PubMed Central

Määttä, M.; Macdonald, H. M.; Mulpuri, K.

2016-01-01

Summary Forearm fractures are common during growth. We studied bone strength in youth with a recent forearm fracture. In girls, suboptimal bone strength was associated with fractures. In boys, poor balance and physical inactivity may lead to fractures. Prospective studies will confirm these relationships and identify targets for prevention strategies. Introduction The etiology of pediatric forearm fractures is unclear. Thus, we examined distal radius bone strength, microstructure, and density in children and adolescents with a recent low- or moderate-energy forearm fracture and those without forearm fractures. Methods We assessed the non-dominant (controls) and non-fractured (cases) distal radius (7 % site) using high-resolution peripheral quantitative computed tomography (HR-pQCT) (Scanco Medical AG) in 270 participants (girls: cases n=47, controls n=61 and boys: cases n=88, controls n=74) aged 8–16 years. We assessed standard anthropometry, maturity, body composition (dual energy X-ray absorptiometry (DXA), Hologic QDR 4500 W) physical activity, and balance. We fit sex-specific logistic regression models for each bone outcome adjusting for maturity, ethnicity, height, and percent body fat. Results In girls, impaired bone strength (failure load, ultimate stress) and a high load-to-strength ratio were associated with low-energy fractures (odds ratios (OR) 2.8–4.3). Low total bone mineral density (Tt.BMD), bone volume ratio, trabecular thickness, and cortical BMD and thickness were also associated with low-energy fractures (ORs 2.0–7.0). In boys, low Tt.BMD, but not bone strength, was associated with low-energy fractures (OR=1.8). Boys with low-energy fractures had poor balance and higher percent body fat compared with controls (p<0.05). Boys with fractures (both types) were less active than controls (p<0.05). Conclusions Forearm fracture etiology appears to be sex-specific. In girls, deficits in bone strength are associated with fractures. In boys, a combination of poor balance, excess body fat, and low physical activity may lead to fractures. Prospective studies are needed to confirm these relationships and clarify targets for prevention strategies. PMID:25572041

Computer system for definition of the quantitative geometry of musculature from CT images.

PubMed

Daniel, Matej; Iglic, Ales; Kralj-Iglic, Veronika; Konvicková, Svatava

2005-02-01

The computer system for quantitative determination of musculoskeletal geometry from computer tomography (CT) images has been developed. The computer system processes series of CT images to obtain three-dimensional (3D) model of bony structures where the effective muscle fibres can be interactively defined. Presented computer system has flexible modular structure and is suitable also for educational purposes.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort.

PubMed

Hastie, Annette T; Martinez, Fernando J; Curtis, Jeffrey L; Doerschuk, Claire M; Hansel, Nadia N; Christenson, Stephanie; Putcha, Nirupama; Ortega, Victor E; Li, Xingnan; Barr, R Graham; Carretta, Elizabeth E; Couper, David J; Cooper, Christopher B; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; O'Neal, Wanda K; Paine, Richard; Peters, Stephen P; Alexis, Neil E; Woodruff, Prescott G; Han, MeiLan K; Meyers, Deborah A; Bleecker, Eugene R

2017-12-01

Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (<200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (<1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV 1 percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8-81·3] vs 75·7% [59·3-90·2], p<0·0001) and after (77·3% [63·1-88·5] vs 82·9% [67·8-95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV 1 percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p<0·0001), but with a high false-discovery rate of 72%. In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. National Institutes of Health, and National Heart, Lung, and Blood Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

Direct Simulation Monte Carlo Application of the Three Dimensional Forced Harmonic Oscillator Model

DTIC Science & Technology

2017-12-07

quasi -classical scattering theory [3,4] or trajectory [5] calculations, semiclassical, as well as close-coupled [6,7] or full [8] quantum mechanical...the quasi -classical trajectory (QCT) calculations approach for ab initio modeling of collision processes. The DMS method builds on an earlier work...nu ar y 30 , 2 01 8 | h ttp :// ar c. ai aa .o rg | D O I: 1 0. 25 14 /1 .T 52 28 to directly use quasi -classical or quantum mechanic

The skeletal structure of insulin-like growth factor I-deficient mice

NASA Technical Reports Server (NTRS)

Bikle, D.; Majumdar, S.; Laib, A.; Powell-Braxton, L.; Rosen, C.; Beamer, W.; Nauman, E.; Leary, C.; Halloran, B.

2001-01-01

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.

Characterization of heterocyclic rings through quantum chemical topology.

PubMed

Griffiths, Mark Z; Popelier, Paul L A

2013-07-22

Five-membered rings are found in a myriad of molecules important in a wide range of areas such as catalysis, nutrition, and drug and agrochemical design. Systematic insight into their largely unexplored chemical space benefits from first principle calculations presented here. This study comprehensively investigates a grand total of 764 different rings, all geometry optimized at the B3LYP/6-311+G(2d,p) level, from the perspective of Quantum Chemical Topology (QCT). For the first time, a 3D space of local topological properties was introduced, in order to characterize rings compactly. This space is called RCP space, after the so-called ring critical point. This space is analogous to BCP space, named after the bond critical point, which compactly and successfully characterizes a chemical bond. The relative positions of the rings in RCP space are determined by the nature of the ring scaffold, such as the heteroatoms within the ring or the number of π-bonds. The summed atomic QCT charges of the five ring atoms revealed five features (number and type of heteroatom, number of π-bonds, substituent and substitution site) that dictate a ring's net charge. Each feature independently contributes toward a ring's net charge. Each substituent has its own distinct and systematic effect on the ring's net charge, irrespective of the ring scaffold. Therefore, this work proves the possibility of designing a ring with specific properties by fine-tuning it through manipulation of these five features.

The pQCT 'Bone Strength Indices' (BSIs, SSI). Relative mechanical impact and diagnostic value of the indicators of bone tissue and design quality employed in their calculation in healthy men and pre- and post-menopausal women.

PubMed

Cointry, G R; Ferretti, J L; Reina, P S; Nocciolino, L M; Rittweger, J; Capozza, R F

2014-03-01

The pQCT-assessed Bone Strength Indices (BSI's, SSI) depend on the product of a 'quality' indicator, the cortical vBMD (vCtD), and a 'design' indicator, one of the cross-sectional moments of inertia or related variables (MIs) in long bones. As the MIs vary naturally much more than the vCtD and represent different properties, it could be that the variation of the indices might not reflect the relative mechanical impact of the variation of their determinant factors in different individuals or circumstances. To understand this problem, we determined the vCtD and MI's in tibia scans of 232 healthy men and pre- and post-MP women, expressed in SD of the means calculated for each group, and analyzed the independent influence of 1 SD unit of variation of each factor on that of the indices by multiple correlations. Results showed: 1. that the independent influence of the MIs on the indices was generally larger than that of the vCtD, and 2. that in post-MP women the influence of the vCtD was larger than it was in the other groups. This confirms the view that inter-individual variation of vCtD is comparatively small, and that mechanical competence of human bone is mostly determined by 'design' factors.

Segmental Bone Regeneration Using a Load Bearing Biodegradable Carrier of Bone Morphogenetic Protein-2

PubMed Central

Chu, Tien-Min G.; Warden, Stuart J.; Turner, Charles H.; Stewart, Rena L.

2006-01-01

Segmental defect regeneration has been a clinical challenge. Current tissue engineering approach using porous biodegradable scaffolds to delivery osteogenic cells and growth factors demonstrated success in facilitating bone regeneration in these cases. However, due to the lack of mechanical property, the porous scaffolds were evaluated in non-load bearing area or were stabilized with stress-shielding devices (bone plate or external fixation). In this paper, we tested a scaffold that does not require a bone plate because it has sufficient biomechanical strength. The tube-shaped scaffolds were manufactured from poly(propylene) fumarate/tricalcium phosphate (PPF/TCP) composites. Dicalcium phosphate dehydrate (DCPD) were used as bone morphogenetic protein -2 (BMP-2) carrier. Twenty two scaffolds were implanted in 5 mm segmental defects in rat femurs stabilized with k-wire for 6 and 15 weeks with and without 10 μg of rhBMP-2. Bridging of the segmental defect was evaluated first radiographically and was confirmed by histology and micro- computer tomography (μ-CT) imaging. The scaffolds in the BMP group maintained the bone length throughout the duration of the study and allow for bridging. The scaffolds in the control group failed to induce bridging and collapsed at 15 weeks. Peripheral computed tomography (pQCT) showed that BMP-2 does not increase the bone mineral density in the callus. Finally, the scaffold in BMP group was found to restore the mechanical property of the rat femur after 15 weeks. Our results demonstrated that the load-bearing BMP-2 scaffold can maintain bone length and allow successfully regeneration in segmental defects. PMID:16996588

Exploring the Perceptions of College Instructors towards Computer Simulation Software Programs: A Quantitative Study

ERIC Educational Resources Information Center

Punch, Raymond J.

2012-01-01

The purpose of the quantitative regression study was to explore and to identify relationships between attitudes toward use and perceptions of value of computer-based simulation programs, of college instructors, toward computer based simulation programs. A relationship has been reported between attitudes toward use and perceptions of the value of…

14 CFR 152.319 - Monitoring and reporting of program performance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... established for the period, made, if applicable, on a quantitative basis related to cost data for computation... established for the period, made, if applicable, on a quantitative basis related to costs for computation of...

14 CFR 152.319 - Monitoring and reporting of program performance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... established for the period, made, if applicable, on a quantitative basis related to cost data for computation... established for the period, made, if applicable, on a quantitative basis related to costs for computation of...

14 CFR 152.319 - Monitoring and reporting of program performance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... established for the period, made, if applicable, on a quantitative basis related to cost data for computation... established for the period, made, if applicable, on a quantitative basis related to costs for computation of...

14 CFR 152.319 - Monitoring and reporting of program performance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... established for the period, made, if applicable, on a quantitative basis related to cost data for computation... established for the period, made, if applicable, on a quantitative basis related to costs for computation of...

14 CFR 152.319 - Monitoring and reporting of program performance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... established for the period, made, if applicable, on a quantitative basis related to cost data for computation... established for the period, made, if applicable, on a quantitative basis related to costs for computation of...

Management Control of Flight Operations (OFC-01) Funds

DTIC Science & Technology

1982-12-01

3uide to Badgeta: y an ~~q.jntContro Svst___. -mpi~,~9 Ivancevich, John M. Szilagyi ,, Jr. kndrew D. and Wallace , Jr. Marc J,, OQ~anizational Bhivior...Sz~iagyi., and Wallace term the socio-techn-Ical systems molel. Showai in Figure 2-1, the molel is an input-transfociatior.-oLtpat system. The system...anA Performance, Goo)dyear Publi-hi-Ef ’ComP~ay,-rIc. T~7777 Ivancevich, John M., Szila; yi, Jr. kardrew D., and Wallace Jr. Marc J., Readi~qct In

The Analysis for Regulation Performance of a Variable Thrust Rocket Engine Control System,

DTIC Science & Technology

1982-06-29

valve: Q,- K .W(t).±K.APN(t) (14) where (15) K-KK (16) ( 17 ) (18) Equations (13) and (14) can be expressed as one equation: . Q(t)-QCt)-Qa(t)-n(" -K:)EQ...Hydraulic pressure when the needle valve starts to rise [g/mm 2 4PH (t)-Hydraulic pressure increment 2 AHHydraulic pressure function area (mm2 B-Needle...rate gain Ke and solenoid valve pressure coefficient K use relatedPH equations (15), (16), ( 17 ) and (18). If we use the parameters of * the exhaust

EnviroLand: A Simple Computer Program for Quantitative Stream Assessment.

ERIC Educational Resources Information Center

Dunnivant, Frank; Danowski, Dan; Timmens-Haroldson, Alice; Newman, Meredith

2002-01-01

Introduces the Enviroland computer program which features lab simulations of theoretical calculations for quantitative analysis and environmental chemistry, and fate and transport models. Uses the program to demonstrate the nature of linear and nonlinear equations. (Author/YDS)

Local Aqueous Solvation Structure Around Ca2+ During Ca2+---Cl– Pair Formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baer, Marcel D.; Mundy, Christopher J.

2016-03-03

The molecular details of single ion solvation around Ca2+ and ion-pairing of Ca2--Cl- are investigated using ab initio molecular dynamics. The use of empirical dispersion corrections to the BLYP functional are investigated by comparison to experimentally available extended X-ray absorption fine structure (EXAFS) measurements, which probes the first solvation shell in great detail. Besides finding differences in the free-energy for both ion-pairing and the coordination number of ion solvation between the quantum and classical descriptions of interaction, there were important differences found between dispersion corrected and uncorrected density functional theory (DFT). Specifically, we show significantly different free-energy landscapes for bothmore » coordination number of Ca2+ and its ion-pairing with Cl- depending on the DFT simulation protocol. Our findings produce a self-consistent treatment of short-range solvent response to the ion and the intermediate to long-range collective response of the electrostatics of the ion-ion interaction to produce a detailed picture of ion-pairing that is consistent with experiment. MDB is supported by MS3 (Materials Synthesis and Simulation Across Scales) Initiative at Pacific Northwest National Laboratory. It was conducted under the Laboratory Directed Research and Development Program at PNNL, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy. CJM acknowledges support from US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Additional computing resources were generously allocated by PNNL's Institutional Computing program. The authors thank Prof. Tom Beck for discussions regarding QCT, and Drs. Greg Schenter and Shawn Kathmann for insightful comments.« less

Analysis of the independent power of age-related, anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study.

PubMed

Reina, P; Cointry, G R; Nocciolino, L; Feldman, S; Ferretti, J L; Rittweger, J; Capozza, R F

2015-03-01

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles' areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue 'quality' (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.

Ab initio-informed maximum entropy modeling of rovibrational relaxation and state-specific dissociation with application to the O2 + O system

NASA Astrophysics Data System (ADS)

Kulakhmetov, Marat; Gallis, Michael; Alexeenko, Alina

2016-05-01

Quasi-classical trajectory (QCT) calculations are used to study state-specific ro-vibrational energy exchange and dissociation in the O2 + O system. Atom-diatom collisions with energy between 0.1 and 20 eV are calculated with a double many body expansion potential energy surface by Varandas and Pais [Mol. Phys. 65, 843 (1988)]. Inelastic collisions favor mono-quantum vibrational transitions at translational energies above 1.3 eV although multi-quantum transitions are also important. Post-collision vibrational favoring decreases first exponentially and then linearly as Δv increases. Vibrationally elastic collisions (Δv = 0) favor small ΔJ transitions while vibrationally inelastic collisions have equilibrium post-collision rotational distributions. Dissociation exhibits both vibrational and rotational favoring. New vibrational-translational (VT), vibrational-rotational-translational (VRT) energy exchange, and dissociation models are developed based on QCT observations and maximum entropy considerations. Full set of parameters for state-to-state modeling of oxygen is presented. The VT energy exchange model describes 22 000 state-to-state vibrational cross sections using 11 parameters and reproduces vibrational relaxation rates within 30% in the 2500-20 000 K temperature range. The VRT model captures 80 × 106 state-to-state ro-vibrational cross sections using 19 parameters and reproduces vibrational relaxation rates within 60% in the 5000-15 000 K temperature range. The developed dissociation model reproduces state-specific and equilibrium dissociation rates within 25% using just 48 parameters. The maximum entropy framework makes it feasible to upscale ab initio simulation to full nonequilibrium flow calculations.

Use of mechanistic simulations as a quantitative risk-ranking tool within the quality by design framework.

PubMed

Stocker, Elena; Toschkoff, Gregor; Sacher, Stephan; Khinast, Johannes G

2014-11-20

The purpose of this study is to evaluate the use of computer simulations for generating quantitative knowledge as a basis for risk ranking and mechanistic process understanding, as required by ICH Q9 on quality risk management systems. In this specific publication, the main focus is the demonstration of a risk assessment workflow, including a computer simulation for the generation of mechanistic understanding of active tablet coating in a pan coater. Process parameter screening studies are statistically planned under consideration of impacts on a potentially critical quality attribute, i.e., coating mass uniformity. Based on computer simulation data the process failure mode and effects analysis of the risk factors is performed. This results in a quantitative criticality assessment of process parameters and the risk priority evaluation of failure modes. The factor for a quantitative reassessment of the criticality and risk priority is the coefficient of variation, which represents the coating mass uniformity. The major conclusion drawn from this work is a successful demonstration of the integration of computer simulation in the risk management workflow leading to an objective and quantitative risk assessment. Copyright © 2014. Published by Elsevier B.V.

Quantitative Prediction of Computational Quality (so the S and C Folks will Accept it)

NASA Technical Reports Server (NTRS)

Hemsch, Michael J.; Luckring, James M.; Morrison, Joseph H.

2004-01-01

Our choice of title may seem strange but we mean each word. In this talk, we are not going to be concerned with computations made "after the fact", i.e. those for which data are available and which are being conducted for explanation and insight. Here we are interested in preventing S&C design problems by finding them through computation before data are available. For such a computation to have any credibility with those who absorb the risk, it is necessary to quantitatively PREDICT the quality of the computational results.

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study.

PubMed

Ostovaneh, Mohammad R; Vavere, Andrea L; Mehra, Vishal C; Kofoed, Klaus F; Matheson, Matthew B; Arbab-Zadeh, Armin; Fujisawa, Yasuko; Schuijf, Joanne D; Rochitte, Carlos E; Scholte, Arthur J; Kitagawa, Kakuya; Dewey, Marc; Cox, Christopher; DiCarli, Marcelo F; George, Richard T; Lima, Joao A C

To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging. The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(p > 0.05 for all). Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Re-examining the surfaces of bone in boys and girls during adolescent growth: a 12-year mixed longitudinal pQCT study

PubMed Central

Gabel, Leigh; Nettlefold, Lindsay; Brasher, Penelope M.; Moore, Sarah; Ahamed, Yasmin; Macdonald, Heather M.; McKay, Heather A.

2016-01-01

We revisit Stanley Garn’s theory related to sex differences in endocortical and periosteal apposition during adolescence using a 12-year mixed longitudinal study design. We used peripheral quantitative computed tomography to examine bone parameters in 230 participants (110 boys, 120 girls; 11.0 yrs at baseline). We assessed total (Tt.Ar, mm2), cortical (Ct.Ar, mm2), and medullary canal area (Me.Ar, mm2), Ct.Ar/Tt.Ar, cortical bone mineral density (Ct.BMD, mg/cm3) and polar strength-strain index (SSIp, mm3) at the tibial midshaft (50% site). We used annual measures of height and chronological age to identify age at peak height velocity (APHV) for each participant. We compared annual accrual rates of bone parameters between boys and girls, aligned on APHV using a linear mixed effects model. At APHV, boys demonstrated greater Tt.Ar (Ratio: 1.27; 95% CI: [1.21, 1.32]), Ct.Ar (1.24; [1.18, 1.30]), Me.Ar (1.31; [1.22, 1.40]) and SSIp (1.36; [1.28, 1.45]), and less Ct.Ar/Tt.Ar (0.98; [0.96, 1.00]) and Ct.BMD (0.97; [0.96, 0.97]) compared with girls. Boys and girls demonstrated periosteal bone formation and net bone loss at the endocortical surface. Compared with girls, boys demonstrated greater annual accrual rates pre-APHV for Tt.Ar (1.18; [1.02, 1.34]) and Me.Ar (1.34; [1.11, 1.57]), lower annual accrual rates pre-APHV for Ct.Ar/Tt.Ar (0.56; [0.29, 0.83]) and Ct.BMD (−0.07; [−0.17, 0.04]) and similar annual accrual rates pre-APHV for Ct.Ar (1.10; [0.94, 1.26]) and SSIp (1.14; [0.98, 1.30]). Post-APHV, boys demonstrated similar annual accrual rates for Ct.Ar/Tt.Ar (1.01; [0.71, 1.31]) and greater annual accrual rates for all other bone parameters compared with girls (Ratio: 1.23 – 2.63; 95% CI: 1.11 to 3.45). Our findings support those of Garn and others of accelerated periosteal apposition during adolescence, more evident in boys than girls. However, our findings challenge the notion of greater endocortical apposition in girls, suggesting instead that girls experience diminished endocortical resorption compared with boys. PMID:26058373

Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls

PubMed Central

Farr, Joshua N.; Chen, Zhao; Lisse, Jeffrey R.; Lohman, Timothy G.; Going, Scott B.

2010-01-01

Understanding the influence of total body fat mass (TBFM) on bone during the peri-pubertal years is critical for the development of future interventions aimed at improving bone strength and reducing fracture risk. Thus, we evaluated the relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and strength at metaphyseal and diaphyseal sites of the femur and tibia of young girls. Data from 396 girls aged 8–13 years from the “Jump-In: Building Better Bones” study were analyzed. Bone parameters were assessed using peripheral quantitative computed tomography (pQCT) at the 4% and 20% distal femur and 4% and 66% distal tibia of the non-dominant leg. Bone parameters at the 4% sites included trabecular vBMD, periosteal circumference, and bone strength index (BSI), while at the 20% femur and 66% tibia, parameters included cortical vBMD, periosteal circumference, and strength-strain index (SSI). Multiple linear regression analyses were used to assess associations between bone parameters and TBFM, controlling for muscle cross-sectional area (MCSA). Regression analyses were then repeated with maturity, bone length, physical activity, and ethnicity as additional covariates. Analysis of covariance (ANCOVA) was used to compare bone parameters among tertiles of TBFM. In regression models with TBFM and MCSA, associations between TBFM and bone parameters at all sites were not significant. TBFM explained very little variance in all bone parameters (0.2–2.3%). In contrast, MCSA was strongly related (p < 0.001) to all bone parameters, except cortical vBMD. The addition of maturity, bone length, physical activity, and ethnicity did not alter the relationship between TBFM and bone parameters. With bone parameters expressed relative to total body mass, ANCOVA showed that all outcomes were significantly (p < 0.001) greater in the lowest compared to the middle and highest tertiles of TBFM. Although TBFM is correlated with femur and tibia vBMD, periosteal circumference, and strength in young girls, this relationship is significantly attenuated after adjustment for MCSA. Nevertheless, girls with higher TBFM relative to body mass have markedly diminished vBMD, geometry, and bone strength at metaphyseal and diaphyseal sites of the femur and tibia. PMID:20060079

Unique effects of energy versus estrogen deficiency on multiple components of bone strength in exercising women.

PubMed

Southmayd, E A; Mallinson, R J; Williams, N I; Mallinson, D J; De Souza, M J

2017-04-01

Many female athletes are energy and/or estrogen deficient, but the independent effects on bone health have not been isolated. Energy deficiency was detrimental at the tibia while estrogen deficiency was detrimental at the radius. Nutrition must be considered alongside menstrual recovery when addressing compromised bone health in female athletes. The purpose of this study was to describe volumetric bone mineral density (vBMD), bone geometry, and estimated bone strength in exercising women (n = 60) grouped according to energy status (energy replete (EnR: n = 30) vs. energy deficient (EnD: n = 30)) and estrogen status (estrogen replete (E 2 R: n = 33) vs. estrogen deficient (E 2 D: n = 27)), resulting in four distinct groups: EnR + E 2 R (n = 17), EnR + E 2 D (n = 13), EnD + E 2 R (n = 16), EnD + E 2 D (n = 14). Energy status was determined using the ratio of measured to predicted resting energy expenditure (mREE/pREE). Estrogen status was based on self-reported menstrual status confirmed by daily evaluation of urinary estrone-1-glucoronide (E1G), pregnanediol glucuronide (PdG), and luteinizing hormone (LH). Eumenorrheic women were considered E 2 R, amenorrheic women were E 2 D, and oligomenorrheic women were categorized based on history of menses in the past year. Bone was assessed using peripheral quantitative computed tomography (pQCT). EnD women exhibited lower total vBMD, trabecular vBMD, cortical area, and BSI at the distal tibia and lower total vBMD, smaller cortical area and cortical thickness, and larger endosteal circumference at the proximal tibia compared to EnR women (p < 0.042). E 2 D women had lower total and cortical vBMD, larger total and trabecular area, and lower BSI at the distal radius and lower cortical vBMD at the proximal radius compared to E 2 R women (p < 0.023). Energy and estrogen interacted to affect total and trabecular area at the distal tibia (p < 0.021). Efforts to correct energy deficiency, which in turn may promote reproductive health, are warranted in order to address the unique contributions of energy status versus estrogen status to bone health.

Skeletal effects of estrogen deficiency as induced by an aromatase inhibitor in an aged male rat model.

PubMed

Vanderschueren, D; Boonen, S; Ederveen, A G; de Coster, R; Van Herck, E; Moermans, K; Vandenput, L; Verstuyf, A; Bouillon, R

2000-11-01

Aromatization of androgens into estrogens may be important for maintenance of the male skeleton. To address this hypothesis, we evaluated the skeletal effects of selective estrogen deficiency as induced by the aromatase inhibitor vorozole (Vor), with or without 17beta-estradiol (E(2)) administration (1.35 microg/day), in aged (12-month-old) male rats. A baseline group was killed at the start of the experiment (Base). The control group (Control), the group treated with vorozole alone (Vor), the group treated with E(2) alone (E(2)), or the group with a combination of both (Vor + E(2)) were killed 15 weeks later. Vorozole significantly increased serum testosterone (T) and reduced serum E(2) compared with Control. Body weight gain and serum insulin-like growth factor-I (IGF-I) were also lower in Vor, whereas significant weight loss and decrease of serum IGF-I occurred as a result of E(2) administration. Bone formation as assessed by serum osteocalcin was unaffected but osteoid surface in the proximal metaphysis of the tibia was increased in Vor-treated rats. Bone resorption as evaluated by urinary deoxypyridinoline excretion was increased in Vor. Biochemical parameters of bone turnover were reduced significantly in all E(2) treated rats. Premature closure of the growth plates and decreased osteoid and mineralizing surfaces were also observed in E(2) and Vor + E(2). Apparent bone density of lumbar vertebrae and femur, as measured by dual-energy X-ray absorptiometry (DXA), was significantly reduced in Vor. Vorozole decreased femoral bone density mainly in the distal femur (trabecular and cortical region). This decrease of bone density was not present in E(2) and Vor + E(2). Similar findings were observed when bone density was assessed by peripheral quantitative computed tomography (pQCT); that is, trabecular density of the distal femur, the proximal tibia, and the distal lumbar vertebra were all lower in Vor. This decrease in density was not observed in all E(2)-treated animals. In conclusion, administration of the aromatase inhibitor, vorozole, to aged male rats induces net trabecular bone loss in both the appendicular and axial skeleton, despite a concomitant increase in serum testosterone. E(2) administration is able to prevent this trabecular bone loss in vorozole-treated animals.

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

PubMed

Kindler, Joseph M; Pollock, Norman K; Laing, Emma M; Oshri, Assaf; Jenkins, Nathan T; Isales, Carlos M; Hamrick, Mark W; Ding, Ke-Hong; Hausman, Dorothy B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

2017-07-01

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p Interaction  < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β Indirect Effect  = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β Indirect Effect  = 0.200, p < 0.001) versus normal (β Indirect Effect  = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Non-reproductive Effects of Anovulation

PubMed Central

Niethammer, B.; Körner, C.; Schmidmayr, M.; Luppa, P. B.; Seifert-Klauss, V. R.

2015-01-01

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17β-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal phase and that of the following cycle. The interaction between ovulation and bone metabolism is complex. Since anovulation may occur in low estrogen states such as pre-anorexic dietary restraint, as well as with high estrogenic circumstances e.g. from functional perimenopausal ovarian cysts, the association with bone changes has been variable in the literature. Accumulating physiological and clinical evidence however point towards a role for ovulation in enhancing bone formation and limiting bone resorption. PMID:26726266

Later Age at Onset of Independent Walking Is Associated With Lower Bone Strength at Fracture-Prone Sites in Older Men.

PubMed

Ireland, Alex; Muthuri, Stella; Rittweger, Joern; Adams, Judith E; Ward, Kate A; Kuh, Diana; Cooper, Rachel

2017-06-01

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height-adjusted hip (standardized regression coefficients with 95% confidence interval [CI] -0.179 [-0.251 to -0.107]), spine (-0.157 [-0.232 to -0.082]), and distal radius (-0.159 [-0.245 to -0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p < 0.001). Adjustment for covariates partially attenuated these associations, primarily because of lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross-sectional moment of inertia [CSMI], indicating bone bending/torsional strength) assessed by hip structural analysis (HSA) from DXA scans. Similar height-adjusted associations were also observed in women for several hip, spine, and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength. Existing interventions effective in hastening walking age may have positive effects on bone across life. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

The influence of disuse on bone microstructure and mechanics assessed by HR-pQCT.

PubMed

Kazakia, Galateia J; Tjong, Willy; Nirody, Jasmine A; Burghardt, Andrew J; Carballido-Gamio, Julio; Patsch, Janina M; Link, Thomas; Feeley, Brian T; Ma, C Benjamin

2014-06-01

Numerous clinical cohorts are exposed to reduced skeletal loading and associated bone loss, including surgical patients, stroke and spinal cord injury victims, and women on bed rest during pregnancy. In this context, understanding disuse-related bone loss is critical to developing interventions to prevent fractures and the associated morbidity, mortality, and cost to the health care system. The aim of this pilot study was to use high-resolution peripheral QCT (HR-pQCT) to examine changes in trabecular and cortical microstructure and biomechanics during a period of non weight bearing (WB) and during recovery following return to normal WB. Surgical patients requiring a 6-week non WB period (n=12, 34.8±7.7 yrs) were scanned at the affected and contralateral tibia prior to surgery, after the 6-week non WB period, and 6 and 13 weeks after returning to full WB. At the affected ultradistal tibia, integral vBMD (including both trabecular and cortical compartments) decreased with respect to baseline (-1.2%), trabecular number increased (+5.6%), while trabecular thickness (-5.4%), separation (-4.6%), and heterogeneity (-7.2%) decreased (all p<0.05). Six weeks after return to full WB, trabecular structure measures reverted to baseline levels. In contrast, integral vBMD continued to decrease after 6 (-2.0%, p<0.05) and 13 weeks (-2.5%, p=0.07) of full WB. At the affected distal site, the disuse period resulted in increased porosity (+16.1%, p<0.005), which remained elevated after 6 weeks (+16.8%, p<0.01) and after 13 weeks (+16.2%, p<0.05). A novel topological analysis applied to the distal tibia cortex demonstrated increased number of canals with surface topology ("slabs" +21.7%, p<0.01) and curve topology ("tubes" +15.0%, p<0.05) as well as increased number of canal junctions (+21.4%, p<0.05) following the disuse period. Porosity increased uniformly through increases in both pore size and number. Finite element analysis at the ultradistal tibia showed decreased stiffness and failure load (-2.8% and -2.4%, p<0.01) following non WB. These biomechanical predictions remained depressed following 6 and 13 weeks of full WB. Finite element analysis at the distal site followed similar trends. Our results suggest that detectable microstructural and biomechanical degradation occurs--particularly within the cortical compartment--as a result of non WB and persists following return to normal loading. A better understanding of these microstructural changes and their short- and long-term influence on biomechanics may have clinical relevance in the context of disuse-related fracture prevention. Copyright © 2014 Elsevier Inc. All rights reserved.

The influence of disuse on bone microstructure and mechanics assessed by HR-pQCT

PubMed Central

Kazakia, Galateia J.; Tjong, Willy; Nirody, Jasmine A.; Burghardt, Andrew J.; Carballido-Gamio, Julio; Patsch, Janina M.; Link, Thomas; Feeley, Brian T.; Ma, C. Benjamin

2014-01-01

Numerous clinical cohorts are exposed to reduced skeletal loading and associated bone loss, including surgical patients, stroke and spinal cord injury victims, and women on bed rest during pregnancy. In this context, understanding disuse-related bone loss is critical to developing interventions to prevent fractures and the associated morbidity, mortality, and cost to the health care system. The aim of this pilot study was to use high-resolution peripheral QCT (HR-pQCT) to examine changes in trabecular and cortical microstructure and biomechanics during a period of non weight bearing (WB) and during recovery following return to normal WB. Surgical patients requiring a 6-week non-WB period (n = 12, 34.8 ± 7.7 yrs) were scanned at the affected and contralateral tibia prior to surgery, after the 6-week non-WB period, and 6 and 13 weeks after returning to full-WB. At the affected ultradistal tibia, integral vBMD (including both trabecular and cortical compartments) decreased with respect to baseline (−1.2%), trabecular number increased (+5.6%), while trabecular thickness (−5.4%), separation (−4.6%), and heterogeneity (−7.2%) decreased (all p<0.05). Six weeks after return to full-WB, trabecular structure measures reverted to baseline levels. In contrast, integral vBMD continued to decrease after 6 (−2.0%, p < 0.05) and 13 weeks (−2.5%, p = 0.07) of full-WB. At the affected distal site, the disuse period resulted in increased porosity (+16.1%, p < 0.005), which remained elevated after 6 weeks (+16.8%, p < 0.01) and after 13 weeks (+16.2%, p < 0.05). A novel topological analysis applied to the distal tibia cortex demonstrated increased number of canals with surface topology (“slabs” +21.7%, p < 0.01) and curve topology (“tubes” +15.0%, p < 0.05) as well as increased number of canal junctions (+21.4%, p < 0.05) following the disuse period. Porosity increased uniformly through increases in both pore size and number. Finite element analysis at the ultradistal tibia showed decreased stiffness and failure load (−2.8% and −2.4%, p < 0.01) following non-WB. These biomechanical predictions remained depressed following 6 and 13 weeks of full-WB. Finite element analysis at the distal site followed similar trends. Our results suggest that detectable microstructural and biomechanical degradation occurs – particularly within the cortical compartment – as a result of non-WB and persists following return to normal loading. A better understanding of these microstructural changes and their short- and long-term influence on biomechanics may have clinical relevance in the context of disuse-related fracture prevention. PMID:24603002

Generalized likelihood ratios for quantitative diagnostic test scores.

PubMed

Tandberg, D; Deely, J J; O'Malley, A J

1997-11-01

The reduction of quantitative diagnostic test scores to the dichotomous case is a wasteful and unnecessary simplification in the era of high-speed computing. Physicians could make better use of the information embedded in quantitative test results if modern generalized curve estimation techniques were applied to the likelihood functions of Bayes' theorem. Hand calculations could be completely avoided and computed graphical summaries provided instead. Graphs showing posttest probability of disease as a function of pretest probability with confidence intervals (POD plots) would enhance acceptance of these techniques if they were immediately available at the computer terminal when test results were retrieved. Such constructs would also provide immediate feedback to physicians when a valueless test had been ordered.

Modeling Students' Problem Solving Performance in the Computer-Based Mathematics Learning Environment

ERIC Educational Resources Information Center

Lee, Young-Jin

2017-01-01

Purpose: The purpose of this paper is to develop a quantitative model of problem solving performance of students in the computer-based mathematics learning environment. Design/methodology/approach: Regularized logistic regression was used to create a quantitative model of problem solving performance of students that predicts whether students can…

Easy calculations of lod scores and genetic risks on small computers.

PubMed Central

Lathrop, G M; Lalouel, J M

1984-01-01

A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139

A Quantitative Study of the Relationship between Leadership Practice and Strategic Intentions to Use Cloud Computing

ERIC Educational Resources Information Center

Castillo, Alan F.

2014-01-01

The purpose of this quantitative correlational cross-sectional research study was to examine a theoretical model consisting of leadership practice, attitudes of business process outsourcing, and strategic intentions of leaders to use cloud computing and to examine the relationships between each of the variables respectively. This study…

Bone microarchitecture in adolescent boys with autism spectrum disorder.

PubMed

Neumeyer, Ann M; Cano Sokoloff, Natalia; McDonnell, Erin; Macklin, Eric A; McDougle, Christopher J; Misra, Madhusmita

2017-04-01

Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD. To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC. Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA). We controlled for age in all groupwise comparisons of HRpQCT and FEA measures. Activity questionnaires, food records, physical exam, and fasting levels of 25(OH) vitamin D and bone markers (C-terminal collagen crosslinks and N-terminal telopeptide (CTX and NTX) for bone resorption, N-terminal propeptide of Type 1 procollagen (P1NP) for bone formation) were obtained. ASD participants were slightly younger than TDC participants (13.6 vs. 14.2years, p=0.44). Tanner stage, height Z-scores and fasting serum bone marker levels did not differ between groups. ASD participants had higher BMI Z-scores, percent body fat, IGF-1 Z-scores, and lower lean mass and aBMD Z-scores than TDC at the WB, WBLH, and femoral neck (P<0.1). At the radius, ASD participants had lower trabecular thickness (0.063 vs. 0.070mm, p=0.004), compressive stiffness (56.7 vs. 69.7kN/mm, p=0.030) and failure load (3.0 vs. 3.7kN, p=0.031) than TDC. ASD participants also had 61% smaller cortical area (6.6 vs. 16.4mm 2 , p=0.051) and thickness (0.08 vs. 0.22mm, p=0.054) compared to TDC. At the tibia, ASD participants had lower compressive stiffness (183 vs. 210kN/mm, p=0.048) and failure load (9.4 vs. 10.8kN, p=0.043) and 23% smaller cortical area (60.3 vs. 81.5mm 2 , p=0.078) compared to TDC. A lower proportion of ASD participants were categorized as "very physically active" (20% vs. 72%, p=0.005). Differences in physical activity, calcium intake and IGF-1 responsiveness may contribute to group differences in stiffness and failure load. Bone microarchitectural parameters are impaired in ASD, with reductions in bone strength estimates (stiffness and failure load) at the ultradistal radius and distal tibia. This may result from lower physical activity and calcium intake, and decreased IGF-1 responsiveness. Copyright © 2017 Elsevier Inc. All rights reserved.

Ab initio-informed maximum entropy modeling of rovibrational relaxation and state-specific dissociation with application to the O{sub 2} + O system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulakhmetov, Marat, E-mail: mkulakhm@purdue.edu; Alexeenko, Alina, E-mail: alexeenk@purdue.edu; Gallis, Michael, E-mail: magalli@sandia.gov

Quasi-classical trajectory (QCT) calculations are used to study state-specific ro-vibrational energy exchange and dissociation in the O{sub 2} + O system. Atom-diatom collisions with energy between 0.1 and 20 eV are calculated with a double many body expansion potential energy surface by Varandas and Pais [Mol. Phys. 65, 843 (1988)]. Inelastic collisions favor mono-quantum vibrational transitions at translational energies above 1.3 eV although multi-quantum transitions are also important. Post-collision vibrational favoring decreases first exponentially and then linearly as Δv increases. Vibrationally elastic collisions (Δv = 0) favor small ΔJ transitions while vibrationally inelastic collisions have equilibrium post-collision rotational distributions. Dissociationmore » exhibits both vibrational and rotational favoring. New vibrational-translational (VT), vibrational-rotational-translational (VRT) energy exchange, and dissociation models are developed based on QCT observations and maximum entropy considerations. Full set of parameters for state-to-state modeling of oxygen is presented. The VT energy exchange model describes 22 000 state-to-state vibrational cross sections using 11 parameters and reproduces vibrational relaxation rates within 30% in the 2500–20 000 K temperature range. The VRT model captures 80 × 10{sup 6} state-to-state ro-vibrational cross sections using 19 parameters and reproduces vibrational relaxation rates within 60% in the 5000–15 000 K temperature range. The developed dissociation model reproduces state-specific and equilibrium dissociation rates within 25% using just 48 parameters. The maximum entropy framework makes it feasible to upscale ab initio simulation to full nonequilibrium flow calculations.« less

Geographic and demographic variabilities of quantitative parameters in stress myocardial computed tomography perfusion.

PubMed

Park, Jinoh; Kim, Hyun-Sook; Hwang, Hye Jeon; Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Kim, Young-Hak

2017-09-01

To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

Parallel and serial computing tools for testing single-locus and epistatic SNP effects of quantitative traits in genome-wide association studies

PubMed Central

Ma, Li; Runesha, H Birali; Dvorkin, Daniel; Garbe, John R; Da, Yang

2008-01-01

Background Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers provide opportunities to detect epistatic SNPs associated with quantitative traits and to detect the exact mode of an epistasis effect. Computational difficulty is the main bottleneck for epistasis testing in large scale GWAS. Results The EPISNPmpi and EPISNP computer programs were developed for testing single-locus and epistatic SNP effects on quantitative traits in GWAS, including tests of three single-locus effects for each SNP (SNP genotypic effect, additive and dominance effects) and five epistasis effects for each pair of SNPs (two-locus interaction, additive × additive, additive × dominance, dominance × additive, and dominance × dominance) based on the extended Kempthorne model. EPISNPmpi is the parallel computing program for epistasis testing in large scale GWAS and achieved excellent scalability for large scale analysis and portability for various parallel computing platforms. EPISNP is the serial computing program based on the EPISNPmpi code for epistasis testing in small scale GWAS using commonly available operating systems and computer hardware. Three serial computing utility programs were developed for graphical viewing of test results and epistasis networks, and for estimating CPU time and disk space requirements. Conclusion The EPISNPmpi parallel computing program provides an effective computing tool for epistasis testing in large scale GWAS, and the epiSNP serial computing programs are convenient tools for epistasis analysis in small scale GWAS using commonly available computer hardware. PMID:18644146

Simulating realistic predator signatures in quantitative fatty acid signature analysis

USGS Publications Warehouse

Bromaghin, Jeffrey F.

2015-01-01

Diet estimation is an important field within quantitative ecology, providing critical insights into many aspects of ecology and community dynamics. Quantitative fatty acid signature analysis (QFASA) is a prominent method of diet estimation, particularly for marine mammal and bird species. Investigators using QFASA commonly use computer simulation to evaluate statistical characteristics of diet estimators for the populations they study. Similar computer simulations have been used to explore and compare the performance of different variations of the original QFASA diet estimator. In both cases, computer simulations involve bootstrap sampling prey signature data to construct pseudo-predator signatures with known properties. However, bootstrap sample sizes have been selected arbitrarily and pseudo-predator signatures therefore may not have realistic properties. I develop an algorithm to objectively establish bootstrap sample sizes that generates pseudo-predator signatures with realistic properties, thereby enhancing the utility of computer simulation for assessing QFASA estimator performance. The algorithm also appears to be computationally efficient, resulting in bootstrap sample sizes that are smaller than those commonly used. I illustrate the algorithm with an example using data from Chukchi Sea polar bears (Ursus maritimus) and their marine mammal prey. The concepts underlying the approach may have value in other areas of quantitative ecology in which bootstrap samples are post-processed prior to their use.

A Computer-Aided Analysis Method of SPECT Brain Images for Quantitative Treatment Monitoring: Performance Evaluations and Clinical Applications.

PubMed

Zheng, Xiujuan; Wei, Wentao; Huang, Qiu; Song, Shaoli; Wan, Jieqing; Huang, Gang

2017-01-01

The objective and quantitative analysis of longitudinal single photon emission computed tomography (SPECT) images are significant for the treatment monitoring of brain disorders. Therefore, a computer aided analysis (CAA) method is introduced to extract a change-rate map (CRM) as a parametric image for quantifying the changes of regional cerebral blood flow (rCBF) in longitudinal SPECT brain images. The performances of the CAA-CRM approach in treatment monitoring are evaluated by the computer simulations and clinical applications. The results of computer simulations show that the derived CRMs have high similarities with their ground truths when the lesion size is larger than system spatial resolution and the change rate is higher than 20%. In clinical applications, the CAA-CRM approach is used to assess the treatment of 50 patients with brain ischemia. The results demonstrate that CAA-CRM approach has a 93.4% accuracy of recovered region's localization. Moreover, the quantitative indexes of recovered regions derived from CRM are all significantly different among the groups and highly correlated with the experienced clinical diagnosis. In conclusion, the proposed CAA-CRM approach provides a convenient solution to generate a parametric image and derive the quantitative indexes from the longitudinal SPECT brain images for treatment monitoring.

Clinical application of a light-pen computer system for quantitative angiography

NASA Technical Reports Server (NTRS)

Alderman, E. L.

1975-01-01

The important features in a clinical system for quantitative angiography were examined. The human interface for data input, whether an electrostatic pen, sonic pen, or light-pen must be engineered to optimize the quality of margin definition. The computer programs which the technician uses for data entry and computation of ventriculographic measurements must be convenient to use on a routine basis in a laboratory performing multiple studies per day. The method used for magnification correction must be continuously monitored.

Laboratory data base for isomer-specific determination of polychlorinated biphenyls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, T.R.; Campbell, R.D.; Stalling, D.L.

1984-07-01

A computer-assisted technique for quantitative determination of polychlorinated biphenyl isomers is described. PCB isomers were identified by use of a retention index system with n-alkyl trichloroacetates as retention index marker compounds. A laboratory data base system was developed to aid in editing and quantitation of data generated from capillary gas chromatographic data. Data base management was provided by computer programs written in DSM-11 (Digital Standard MUMPS) for the PDP-11 family of computers. 13 references, 4 figures, 2 tables.

Clinical and mathematical introduction to computer processing of scintigraphic images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goris, M.L.; Briandet, P.A.

The authors state in their preface:''...we believe that there is no book yet available in which computing in nuclear medicine has been approached in a reasonable manner. This book is our attempt to correct the situation.'' The book is divided into four sections: (1) Clinical Applications of Quantitative Scintigraphic Analysis; (2) Mathematical Derivations; (3) Processing Methods of Scintigraphic Images; and (4) The (Computer) System. Section 1 has chapters on quantitative approaches to congenital and acquired heart diseases, nephrology and urology, and pulmonary medicine.

Effects of Computer Programming on Students' Cognitive Performance: A Quantitative Synthesis.

ERIC Educational Resources Information Center

Liao, Yuen-Kuang Cliff

A meta-analysis was performed to synthesize existing data concerning the effects of computer programing on cognitive outcomes of students. Sixty-five studies were located from three sources, and their quantitative data were transformed into a common scale--Effect Size (ES). The analysis showed that 58 (89%) of the study-weighted ESs were positive…

Poem Generator: A Comparative Quantitative Evaluation of a Microworlds-Based Learning Approach for Teaching English

ERIC Educational Resources Information Center

Jenkins, Craig

2015-01-01

This paper is a comparative quantitative evaluation of an approach to teaching poetry in the subject domain of English that employs a "guided discovery" pedagogy using computer-based microworlds. It uses a quasi-experimental design in order to measure performance gains in computational thinking and poetic thinking following a…

The simultaneous quantitation of ten amino acids in soil extracts by mass fragmentography

NASA Technical Reports Server (NTRS)

Pereira, W. E.; Hoyano, Y.; Reynolds, W. E.; Summons, R. E.; Duffield, A. M.

1972-01-01

A specific and sensitive method for the identification and simultaneous quantitation by mass fragmentography of ten of the amino acids present in soil was developed. The technique uses a computer driven quadrupole mass spectrometer and a commercial preparation of deuterated amino acids is used as internal standards for purposes of quantitation. The results obtained are comparable with those from an amino acid analyzer. In the quadrupole mass spectrometer-computer system up to 25 pre-selected ions may be monitored sequentially. This allows a maximum of 12 different amino acids (one specific ion in each of the undeuterated and deuterated amino acid spectra) to be quantitated. The method is relatively rapid (analysis time of approximately one hour) and is capable of the quantitation of nanogram quantities of amino acids.

State-to-state models of vibrational relaxation in Direct Simulation Monte Carlo (DSMC)

NASA Astrophysics Data System (ADS)

Oblapenko, G. P.; Kashkovsky, A. V.; Bondar, Ye A.

2017-02-01

In the present work, the application of state-to-state models of vibrational energy exchanges to the Direct Simulation Monte Carlo (DSMC) is considered. A state-to-state model for VT transitions of vibrational energy in nitrogen and oxygen, based on the application of the inverse Laplace transform to results of quasiclassical trajectory calculations (QCT) of vibrational energy transitions, along with the Forced Harmonic Oscillator (FHO) state-to-state model is implemented in DSMC code and applied to flows around blunt bodies. Comparisons are made with the widely used Larsen-Borgnakke model and the in uence of multi-quantum VT transitions is assessed.

Least squares QR-based decomposition provides an efficient way of computing optimal regularization parameter in photoacoustic tomography.

PubMed

Shaw, Calvin B; Prakash, Jaya; Pramanik, Manojit; Yalavarthy, Phaneendra K

2013-08-01

A computationally efficient approach that computes the optimal regularization parameter for the Tikhonov-minimization scheme is developed for photoacoustic imaging. This approach is based on the least squares-QR decomposition which is a well-known dimensionality reduction technique for a large system of equations. It is shown that the proposed framework is effective in terms of quantitative and qualitative reconstructions of initial pressure distribution enabled via finding an optimal regularization parameter. The computational efficiency and performance of the proposed method are shown using a test case of numerical blood vessel phantom, where the initial pressure is exactly known for quantitative comparison.

Computational Toxicology (S)

EPA Science Inventory

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. Th...

A specialized plug-in software module for computer-aided quantitative measurement of medical images.

PubMed

Wang, Q; Zeng, Y J; Huo, P; Hu, J L; Zhang, J H

2003-12-01

This paper presents a specialized system for quantitative measurement of medical images. Using Visual C++, we developed a computer-aided software based on Image-Pro Plus (IPP), a software development platform. When transferred to the hard disk of a computer by an MVPCI-V3A frame grabber, medical images can be automatically processed by our own IPP plug-in for immunohistochemical analysis, cytomorphological measurement and blood vessel segmentation. In 34 clinical studies, the system has shown its high stability, reliability and ease of utility.

Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology

EPA Science Inventory

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...

Prediction of Environmental Impact of High-Energy Materials with Atomistic Computer Simulations

DTIC Science & Technology

2010-11-01

from a training set of compounds. Other methods include Quantitative Struc- ture-Activity Relationship ( QSAR ) and Quantitative Structure-Property...26 28 the development of QSPR/ QSAR models, in contrast to boiling points and critical parameters derived from empirical correlations, to improve...Quadratic Configuration Interaction Singles Doubles QSAR Quantitative Structure-Activity Relationship QSPR Quantitative Structure-Property

Anniversary Paper: History and status of CAD and quantitative image analysis: The role of Medical Physics and AAPM

PubMed Central

Giger, Maryellen L.; Chan, Heang-Ping; Boone, John

2008-01-01

The roles of physicists in medical imaging have expanded over the years, from the study of imaging systems (sources and detectors) and dose to the assessment of image quality and perception, the development of image processing techniques, and the development of image analysis methods to assist in detection and diagnosis. The latter is a natural extension of medical physicists’ goals in developing imaging techniques to help physicians acquire diagnostic information and improve clinical decisions. Studies indicate that radiologists do not detect all abnormalities on images that are visible on retrospective review, and they do not always correctly characterize abnormalities that are found. Since the 1950s, the potential use of computers had been considered for analysis of radiographic abnormalities. In the mid-1980s, however, medical physicists and radiologists began major research efforts for computer-aided detection or computer-aided diagnosis (CAD), that is, using the computer output as an aid to radiologists—as opposed to a completely automatic computer interpretation—focusing initially on methods for the detection of lesions on chest radiographs and mammograms. Since then, extensive investigations of computerized image analysis for detection or diagnosis of abnormalities in a variety of 2D and 3D medical images have been conducted. The growth of CAD over the past 20 years has been tremendous—from the early days of time-consuming film digitization and CPU-intensive computations on a limited number of cases to its current status in which developed CAD approaches are evaluated rigorously on large clinically relevant databases. CAD research by medical physicists includes many aspects—collecting relevant normal and pathological cases; developing computer algorithms appropriate for the medical interpretation task including those for segmentation, feature extraction, and classifier design; developing methodology for assessing CAD performance; validating the algorithms using appropriate cases to measure performance and robustness; conducting observer studies with which to evaluate radiologists in the diagnostic task without and with the use of the computer aid; and ultimately assessing performance with a clinical trial. Medical physicists also have an important role in quantitative imaging, by validating the quantitative integrity of scanners and developing imaging techniques, and image analysis tools that extract quantitative data in a more accurate and automated fashion. As imaging systems become more complex and the need for better quantitative information from images grows, the future includes the combined research efforts from physicists working in CAD with those working on quantitative imaging systems to readily yield information on morphology, function, molecular structure, and more—from animal imaging research to clinical patient care. A historical review of CAD and a discussion of challenges for the future are presented here, along with the extension to quantitative image analysis. PMID:19175137

Anniversary Paper: History and status of CAD and quantitative image analysis: The role of Medical Physics and AAPM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giger, Maryellen L.; Chan, Heang-Ping; Boone, John

2008-12-15

The roles of physicists in medical imaging have expanded over the years, from the study of imaging systems (sources and detectors) and dose to the assessment of image quality and perception, the development of image processing techniques, and the development of image analysis methods to assist in detection and diagnosis. The latter is a natural extension of medical physicists' goals in developing imaging techniques to help physicians acquire diagnostic information and improve clinical decisions. Studies indicate that radiologists do not detect all abnormalities on images that are visible on retrospective review, and they do not always correctly characterize abnormalities thatmore » are found. Since the 1950s, the potential use of computers had been considered for analysis of radiographic abnormalities. In the mid-1980s, however, medical physicists and radiologists began major research efforts for computer-aided detection or computer-aided diagnosis (CAD), that is, using the computer output as an aid to radiologists--as opposed to a completely automatic computer interpretation--focusing initially on methods for the detection of lesions on chest radiographs and mammograms. Since then, extensive investigations of computerized image analysis for detection or diagnosis of abnormalities in a variety of 2D and 3D medical images have been conducted. The growth of CAD over the past 20 years has been tremendous--from the early days of time-consuming film digitization and CPU-intensive computations on a limited number of cases to its current status in which developed CAD approaches are evaluated rigorously on large clinically relevant databases. CAD research by medical physicists includes many aspects--collecting relevant normal and pathological cases; developing computer algorithms appropriate for the medical interpretation task including those for segmentation, feature extraction, and classifier design; developing methodology for assessing CAD performance; validating the algorithms using appropriate cases to measure performance and robustness; conducting observer studies with which to evaluate radiologists in the diagnostic task without and with the use of the computer aid; and ultimately assessing performance with a clinical trial. Medical physicists also have an important role in quantitative imaging, by validating the quantitative integrity of scanners and developing imaging techniques, and image analysis tools that extract quantitative data in a more accurate and automated fashion. As imaging systems become more complex and the need for better quantitative information from images grows, the future includes the combined research efforts from physicists working in CAD with those working on quantitative imaging systems to readily yield information on morphology, function, molecular structure, and more--from animal imaging research to clinical patient care. A historical review of CAD and a discussion of challenges for the future are presented here, along with the extension to quantitative image analysis.« less

Clinical application of a light-pen computer system for quantitative angiography

NASA Technical Reports Server (NTRS)

Alderman, E. L.

1975-01-01

The paper describes an angiographic analysis system which uses a video disk for recording and playback, a light-pen for data input, minicomputer processing, and an electrostatic printer/plotter for hardcopy output. The method is applied to quantitative analysis of ventricular volumes, sequential ventriculography for assessment of physiologic and pharmacologic interventions, analysis of instantaneous time sequence of ventricular systolic and diastolic events, and quantitation of segmental abnormalities. The system is shown to provide the capability for computation of ventricular volumes and other measurements from operator-defined margins by greatly reducing the tedium and errors associated with manual planimetry.

Quantitative relations between fishing mortality, spawning stress mortality and biomass growth rate (computed with numerical model FISHMO)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laevastu, T.

1983-01-01

The effects of fishing on a given species biomass have been quantitatively evaluated. A constant recruitment is assumed in this study, but the evaluation can be computed on any known age distribution of exploitable biomass. Fishing mortality is assumed to be constant with age; however, spawning stress mortality increases with age. When fishing (mortality) increases, the spawning stress mortality decreases relative to total and exploitable biomasses. These changes are quantitatively shown for two species from the Bering Sea - walleye pollock, Theragra chalcogramma, and yellowfin sole, Limanda aspera.

Computing Quantitative Characteristics of Finite-State Real-Time Systems

DTIC Science & Technology

1994-05-04

Current methods for verifying real - time systems are essentially decision procedures that establish whether the system model satisfies a given...specification. We present a general method for computing quantitative information about finite-state real - time systems . We have developed algorithms that...our technique can be extended to a more general representation of real - time systems , namely, timed transition graphs. The algorithms presented in this

Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology.

PubMed

Bonham, Kevin S; Stefan, Melanie I

2017-10-01

While women are generally underrepresented in STEM fields, there are noticeable differences between fields. For instance, the gender ratio in biology is more balanced than in computer science. We were interested in how this difference is reflected in the interdisciplinary field of computational/quantitative biology. To this end, we examined the proportion of female authors in publications from the PubMed and arXiv databases. There are fewer female authors on research papers in computational biology, as compared to biology in general. This is true across authorship position, year, and journal impact factor. A comparison with arXiv shows that quantitative biology papers have a higher ratio of female authors than computer science papers, placing computational biology in between its two parent fields in terms of gender representation. Both in biology and in computational biology, a female last author increases the probability of other authors on the paper being female, pointing to a potential role of female PIs in influencing the gender balance.

Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine Images

PubMed Central

Frey, Eric C.; Humm, John L.; Ljungberg, Michael

2012-01-01

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. PMID:22475429

CMEIAS color segmentation: an improved computing technology to process color images for quantitative microbial ecology studies at single-cell resolution.

PubMed

Gross, Colin A; Reddy, Chandan K; Dazzo, Frank B

2010-02-01

Quantitative microscopy and digital image analysis are underutilized in microbial ecology largely because of the laborious task to segment foreground object pixels from background, especially in complex color micrographs of environmental samples. In this paper, we describe an improved computing technology developed to alleviate this limitation. The system's uniqueness is its ability to edit digital images accurately when presented with the difficult yet commonplace challenge of removing background pixels whose three-dimensional color space overlaps the range that defines foreground objects. Image segmentation is accomplished by utilizing algorithms that address color and spatial relationships of user-selected foreground object pixels. Performance of the color segmentation algorithm evaluated on 26 complex micrographs at single pixel resolution had an overall pixel classification accuracy of 99+%. Several applications illustrate how this improved computing technology can successfully resolve numerous challenges of complex color segmentation in order to produce images from which quantitative information can be accurately extracted, thereby gain new perspectives on the in situ ecology of microorganisms. Examples include improvements in the quantitative analysis of (1) microbial abundance and phylotype diversity of single cells classified by their discriminating color within heterogeneous communities, (2) cell viability, (3) spatial relationships and intensity of bacterial gene expression involved in cellular communication between individual cells within rhizoplane biofilms, and (4) biofilm ecophysiology based on ribotype-differentiated radioactive substrate utilization. The stand-alone executable file plus user manual and tutorial images for this color segmentation computing application are freely available at http://cme.msu.edu/cmeias/ . This improved computing technology opens new opportunities of imaging applications where discriminating colors really matter most, thereby strengthening quantitative microscopy-based approaches to advance microbial ecology in situ at individual single-cell resolution.

Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement

PubMed Central

Lee, Hyunjong; Kim, Ji Hyun; Kang, Yeon-koo; Moon, Jae Hoon; So, Young; Lee, Won Woo

2016-01-01

Abstract Objectives: Technetium pertechnetate (99mTcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of 99mTcO4. Here, we investigated the usefulness of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) after injection of 99mTcO4 in detecting thyroid function abnormalities. Materials and methods: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 ± 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent 99mTcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. Results: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal–Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other 99mTcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. Conclusions: Quantitative SPECT/CT is more accurate than conventional TUS for measuring 99mTcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID:27399139

Attitudes towards Computer and Computer Self-Efficacy as Predictors of Preservice Mathematics Teachers' Computer Anxiety

ERIC Educational Resources Information Center

Awofala, Adeneye O. A.; Akinoso, Sabainah O.; Fatade, Alfred O.

2017-01-01

The study investigated attitudes towards computer and computer self-efficacy as predictors of computer anxiety among 310 preservice mathematics teachers from five higher institutions of learning in Lagos and Ogun States of Nigeria using the quantitative research method within the blueprint of the descriptive survey design. Data collected were…

Autoradiographic method for quantitation of deposition and distribution of radiocalcium in bone

PubMed Central

Lawrence Riggs, B; Bassingthwaighte, James B.; Jowsey, Jenifer; Peter Pequegnat, E

2010-01-01

A method is described for quantitating autoradiographs of bone-seeking isotopes in microscopic sections of bone. Autoradiographs of bone sections containing 45Ca and internal calibration standards are automatically scanned with a microdensitometer. The digitized optical density output is stored on magnetic tape and is converted by computer to equivalent activity of 45Ca per gram of bone. The computer determines the total 45Ca uptake in the bone section and, on the basis of optical density and anatomic position, quantitatively divides the uptake into 4 components, each representing a separate physiologic process (bone formation, secondary mineralization, diffuse long-term exchange, and surface short-term exchange). The method is also applicable for quantitative analysis of microradiographs of bone sections for mineral content and density. PMID:5416906

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis.

PubMed

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young; Lee, Won Woo

2018-01-01

Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol ( p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake ( p = 0.004), SUVmean ( p < 0.001), SUVmax ( p = 0.002), and functional thyroid mass ( p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism ( p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 - 1.035). Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Preparing systems engineering and computing science students in disciplined methods, quantitative, and advanced statistical techniques to improve process performance

NASA Astrophysics Data System (ADS)

McCray, Wilmon Wil L., Jr.

The research was prompted by a need to conduct a study that assesses process improvement, quality management and analytical techniques taught to students in U.S. colleges and universities undergraduate and graduate systems engineering and the computing science discipline (e.g., software engineering, computer science, and information technology) degree programs during their academic training that can be applied to quantitatively manage processes for performance. Everyone involved in executing repeatable processes in the software and systems development lifecycle processes needs to become familiar with the concepts of quantitative management, statistical thinking, process improvement methods and how they relate to process-performance. Organizations are starting to embrace the de facto Software Engineering Institute (SEI) Capability Maturity Model Integration (CMMI RTM) Models as process improvement frameworks to improve business processes performance. High maturity process areas in the CMMI model imply the use of analytical, statistical, quantitative management techniques, and process performance modeling to identify and eliminate sources of variation, continually improve process-performance; reduce cost and predict future outcomes. The research study identifies and provides a detail discussion of the gap analysis findings of process improvement and quantitative analysis techniques taught in U.S. universities systems engineering and computing science degree programs, gaps that exist in the literature, and a comparison analysis which identifies the gaps that exist between the SEI's "healthy ingredients " of a process performance model and courses taught in U.S. universities degree program. The research also heightens awareness that academicians have conducted little research on applicable statistics and quantitative techniques that can be used to demonstrate high maturity as implied in the CMMI models. The research also includes a Monte Carlo simulation optimization model and dashboard that demonstrates the use of statistical methods, statistical process control, sensitivity analysis, quantitative and optimization techniques to establish a baseline and predict future customer satisfaction index scores (outcomes). The American Customer Satisfaction Index (ACSI) model and industry benchmarks were used as a framework for the simulation model.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

PubMed Central

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young

2018-01-01

Objective Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Materials and Methods Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. Results All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). Conclusion Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism. PMID:29713225

Resources and Approaches for Teaching Quantitative and Computational Skills in the Geosciences and Allied Fields

NASA Astrophysics Data System (ADS)

Orr, C. H.; Mcfadden, R. R.; Manduca, C. A.; Kempler, L. A.

2016-12-01

Teaching with data, simulations, and models in the geosciences can increase many facets of student success in the classroom, and in the workforce. Teaching undergraduates about programming and improving students' quantitative and computational skills expands their perception of Geoscience beyond field-based studies. Processing data and developing quantitative models are critically important for Geoscience students. Students need to be able to perform calculations, analyze data, create numerical models and visualizations, and more deeply understand complex systems—all essential aspects of modern science. These skills require students to have comfort and skill with languages and tools such as MATLAB. To achieve comfort and skill, computational and quantitative thinking must build over a 4-year degree program across courses and disciplines. However, in courses focused on Geoscience content it can be challenging to get students comfortable with using computational methods to answers Geoscience questions. To help bridge this gap, we have partnered with MathWorks to develop two workshops focused on collecting and developing strategies and resources to help faculty teach students to incorporate data, simulations, and models into the curriculum at the course and program levels. We brought together faculty members from the sciences, including Geoscience and allied fields, who teach computation and quantitative thinking skills using MATLAB to build a resource collection for teaching. These materials, and the outcomes of the workshops are freely available on our website. The workshop outcomes include a collection of teaching activities, essays, and course descriptions that can help faculty incorporate computational skills at the course or program level. The teaching activities include in-class assignments, problem sets, labs, projects, and toolboxes. These activities range from programming assignments to creating and using models. The outcomes also include workshop syntheses that highlights best practices, a set of webpages to support teaching with software such as MATLAB, and an interest group actively discussing aspects these issues in Geoscience and allied fields. Learn more and view the resources at http://serc.carleton.edu/matlab_computation2016/index.html

The Influence of Reconstruction Kernel on Bone Mineral and Strength Estimates Using Quantitative Computed Tomography and Finite Element Analysis.

PubMed

Michalski, Andrew S; Edwards, W Brent; Boyd, Steven K

2017-10-17

Quantitative computed tomography has been posed as an alternative imaging modality to investigate osteoporosis. We examined the influence of computed tomography convolution back-projection reconstruction kernels on the analysis of bone quantity and estimated mechanical properties in the proximal femur. Eighteen computed tomography scans of the proximal femur were reconstructed using both a standard smoothing reconstruction kernel and a bone-sharpening reconstruction kernel. Following phantom-based density calibration, we calculated typical bone quantity outcomes of integral volumetric bone mineral density, bone volume, and bone mineral content. Additionally, we performed finite element analysis in a standard sideways fall on the hip loading configuration. Significant differences for all outcome measures, except integral bone volume, were observed between the 2 reconstruction kernels. Volumetric bone mineral density measured using images reconstructed by the standard kernel was significantly lower (6.7%, p < 0.001) when compared with images reconstructed using the bone-sharpening kernel. Furthermore, the whole-bone stiffness and the failure load measured in images reconstructed by the standard kernel were significantly lower (16.5%, p < 0.001, and 18.2%, p < 0.001, respectively) when compared with the image reconstructed by the bone-sharpening kernel. These data suggest that for future quantitative computed tomography studies, a standardized reconstruction kernel will maximize reproducibility, independent of the use of a quantitative calibration phantom. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Multimodal computational microscopy based on transport of intensity equation

NASA Astrophysics Data System (ADS)

Li, Jiaji; Chen, Qian; Sun, Jiasong; Zhang, Jialin; Zuo, Chao

2016-12-01

Transport of intensity equation (TIE) is a powerful tool for phase retrieval and quantitative phase imaging, which requires intensity measurements only at axially closely spaced planes without a separate reference beam. It does not require coherent illumination and works well on conventional bright-field microscopes. The quantitative phase reconstructed by TIE gives valuable information that has been encoded in the complex wave field by passage through a sample of interest. Such information may provide tremendous flexibility to emulate various microscopy modalities computationally without requiring specialized hardware components. We develop a requisite theory to describe such a hybrid computational multimodal imaging system, which yields quantitative phase, Zernike phase contrast, differential interference contrast, and light field moment imaging, simultaneously. It makes the various observations for biomedical samples easy. Then we give the experimental demonstration of these ideas by time-lapse imaging of live HeLa cell mitosis. Experimental results verify that a tunable lens-based TIE system, combined with the appropriate postprocessing algorithm, can achieve a variety of promising imaging modalities in parallel with the quantitative phase images for the dynamic study of cellular processes.

The dynamic behavior of a liquid ethanol-water mixture: a perspective from quantum chemical topology.

PubMed

Mejía, Sol M; Mills, Matthew J L; Shaik, Majeed S; Mondragon, Fanor; Popelier, Paul L A

2011-05-07

Quantum Chemical Topology (QCT) is used to reveal the dynamics of atom-atom interactions in a liquid. A molecular dynamics simulation was carried out on an ethanol-water liquid mixture at its azeotropic concentration (X(ethanol)=0.899), using high-rank multipolar electrostatics. A thousand (ethanol)(9)-water heterodecamers, respecting the water-ethanol ratio of the azeotropic mixture, were extracted from the simulation. Ab initio electron densities were computed at the B3LYP/6-31+G(d) level for these molecular clusters. A video shows the dynamical behavior of a pattern of bond critical points and atomic interaction lines, fluctuating over 1 ns. A bond critical point distribution revealed the fluctuating behavior of water and ethanol molecules in terms of O-H···O, C-H···O and H···H interactions. Interestingly, the water molecule formed one to six C-H···O and one to four O-H···O interactions as a proton acceptor. We found that the more localized a dynamical bond critical point distribution, the higher the average electron density at its bond critical points. The formation of multiple C-H···O interactions affected the shape of the oxygen basin of the water molecule, which is shown in three dimensions. The hydrogen atoms of water strongly preferred to form H···H interactions with ethanol's alkyl hydrogen atoms over its hydroxyl hydrogen. This journal is © the Owner Societies 2011

Quantitative computed tomography and aerosol morphometry in COPD and alpha1-antitrypsin deficiency.

PubMed

Shaker, S B; Maltbaek, N; Brand, P; Haeussermann, S; Dirksen, A

2005-01-01

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD). Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with alpha1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity. In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group. In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with alpha1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.

Quantitative Study on Computer Self-Efficacy and Computer Anxiety Differences in Academic Major and Residential Status

ERIC Educational Resources Information Center

Binkley, Zachary Wayne McClellan

2017-01-01

This study investigates computer self-efficacy and computer anxiety within 61 students across two academic majors, Aviation and Sports and Exercise Science, while investigating the impact residential status, age, and gender has on those two psychological constructs. The purpose of the study is to find if computer self-efficacy and computer anxiety…

Slicing for Biology.

ERIC Educational Resources Information Center

Ekstrom, James

2001-01-01

Advocates using computer imaging technology to assist students in doing projects in which determining density is important. Students can study quantitative comparisons of masses, lengths, and widths using computer software. Includes figures displaying computer images of shells, yeast cultures, and the Aral Sea. (SAH)

Exposure Science and the US EPA National Center for Computational Toxicology

EPA Science Inventory

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. The...

Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology

PubMed Central

2017-01-01

While women are generally underrepresented in STEM fields, there are noticeable differences between fields. For instance, the gender ratio in biology is more balanced than in computer science. We were interested in how this difference is reflected in the interdisciplinary field of computational/quantitative biology. To this end, we examined the proportion of female authors in publications from the PubMed and arXiv databases. There are fewer female authors on research papers in computational biology, as compared to biology in general. This is true across authorship position, year, and journal impact factor. A comparison with arXiv shows that quantitative biology papers have a higher ratio of female authors than computer science papers, placing computational biology in between its two parent fields in terms of gender representation. Both in biology and in computational biology, a female last author increases the probability of other authors on the paper being female, pointing to a potential role of female PIs in influencing the gender balance. PMID:29023441

Bone accrual in oligo-amenorrheic athletes, eumenorrheic athletes and non-athletes.

PubMed

Singhal, Vibha; Reyes, Karen Campoverde; Pfister, Brooke; Ackerman, Kathryn; Slattery, Meghan; Cooper, Katherine; Toth, Alexander; Gupta, Nupur; Goldstein, Mark; Eddy, Kamryn; Misra, Madhusmita

2018-05-11

Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults. Evaluate differences in bone accrual over 12 months in OA, eumenorrheic athletes (EA) and non-athletes (NA). We hypothesized that bone accrual would be lower in OA than EA and NA, with differences most pronounced at non-weight bearing trabecular sites. 27 OA, 29 EA, and 22 NA, 14-25 years old, completed 12-months of the prospective study. Athletes were weight-bearing endurance athletes. Subjects were assessed for areal BMD and bone mineral content (BMC) using DXA at the femoral neck, total hip, lumbar spine and whole body (WB). Failure load (a strength estimate) at the distal radius and tibia was assessed using microfinite element analysis of data obtained via high resolution peripheral quantitative computed tomography (HRpQCT). The primary analysis was a comparison of changes in areal BMD, BMC, and failure load across groups over 12-months at the respective sites. Groups did not differ for baseline age, height or BMI. Percent body fat was lower in both OA and EA compared to NA. OA attained menarche later than EA and NA. Over the follow-up period, OA gained 1.9 ± 2.7 kg of weight compared to 0.5 ± 2.4 kg and 0.8 ± 2.3 kg in EA and NA respectively (p = 0.09); 39% of OA resumed menses. Changes in BMD, BMD Z-scores, and tibial failure load over 12-months did not differ among groups. At follow up, EA had higher femoral neck, hip and WB BMD Z-scores than NA, and higher hip BMD Z-scores than OA (p < 0.05) after adjusting for covariates. At follow-up, radial failure load was lower in OA vs. NA, and tibial failure load lower in OA and NA vs. EA (p ≤ 0.04 for all). Change in weight and fat mass were associated with changes in BMD measures at multiple sites. Despite weight gain and menses recovery in many OA during follow-up, residual deficits persist without catch-up raising concerns for suboptimal peak bone mass acquisition. Copyright © 2017. Published by Elsevier Inc.

Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation.

PubMed

Frederiksen, A L; Hansen, S; Brixen, K; Frost, M

2014-12-01

Short-stature homeobox (SHOX) gene haploinsufficiency may cause skeletal dysplasia including Léri-Weill Dyschondrosteosis (LWD), a clinical entity characterised by the triad of low height, mesomelic disproportion and Madelung's deformity of the wrist. Bone microarchitecture and estimated strength in adult SHOX mutation carriers have not been examined. Twenty-two subjects with a SHOX mutation including 7 males and 15 females with a median age of 38.8 [21.1-52.2] years were recruited from five unrelated families. The control group consisted of 22 healthy subjects matched on age and sex. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric density, microarchitecture and finite element estimated (FEA) bone strength were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). A full region of interest (ROI) image analysis and height-matched ROI analyses adjusting for differences in body height between the two groups were performed. Areal BMD and T-scores showed no significant differences between cases and controls. Total radius area was smaller in cases than controls (207 [176-263] vs. 273 [226-298] mm, p<0.01). Radius cortical bone area (74 ± 20 vs. 58 ± 17 mm(2), p=0.01) and thickness (1.16 ± 0.30 vs. 0.84 ± 0.26 mm, p<0.01) as well as total density (428 ± 99 vs. 328 ± 72 mg/cm(3), p<0.01) were higher in SHOX mutation carriers compared to controls. Radius trabecular bone area (119 [103-192] vs. 202 [168-247] mm(2), p<0.01) and trabecular number (1.61 [1.46-2.07] vs. 1.89 [1.73-2.08] mm(-1), p=0.01) were smaller in SHOX mutation carriers. Tibia trabecular thickness was lower in cases (0.067 ± 0.012 vs. 0.076 ± 0.012 mm, p=0.01). These results remained significant after adjustment for differences in body height and when restricting analyses to females. There were no differences in BMD, radius and tibia cortical porosity or FEA failure load between groups. A segment of cortical bone defect was identified in the distal radius adjacent to ulna in five unrelated SHOX mutation carriers. Subjects with a SHOX mutation presented with a different bone geometry in radius and tibia while there were no differences in BMD or failure load compared to controls, suggesting that mutations in SHOX gene may have an impact on bone microarchitecture albeit not bone strength. Copyright © 2014 Elsevier Inc. All rights reserved.

Non-reproductive Effects of Anovulation: Bone Metabolism in the Luteal Phase of Premenopausal Women Differs between Ovulatory and Anovulatory Cycles.

PubMed

Niethammer, B; Körner, C; Schmidmayr, M; Luppa, P B; Seifert-Klauss, V R

2015-12-01

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17β-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal phase and that of the following cycle. The interaction between ovulation and bone metabolism is complex. Since anovulation may occur in low estrogen states such as pre-anorexic dietary restraint, as well as with high estrogenic circumstances e.g. from functional perimenopausal ovarian cysts, the association with bone changes has been variable in the literature. Accumulating physiological and clinical evidence however point towards a role for ovulation in enhancing bone formation and limiting bone resorption.

Skeletal and dental effects on rats following in utero/lactational exposure to the non-dioxin-like polychlorinated biphenyl PCB 180

PubMed Central

Romero, Ashly N.; Herlin, Maria; Finnilä, Mikko; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

2017-01-01

Polychlorinated biphenyls (PCBs) are a large class of persistent organic pollutants that are potentially harmful to human and wildlife health. Although a small number of dioxin-like (DL) PCBs are well characterized, the majority of PCBs have non-dioxin-like (NDL) modes of action and biological effects that are less understood. We conducted a dose-response study of the skeletal and dental effects of in utero/lactational exposure to 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180), a NDL PCB congener that is abundantly present in the environment and foods, including mother’s milk. In a sample of 35- and 84-day-old male and female offspring from pregnant rats exposed to different doses of PCB 180 (0, 10, 30, 100, 300, and 1000 mg/kg bw), we measured the three-dimensional (3D) coordinates of 27 landmarks on the craniofacial skeleton with a Microscribe G2X system, the buccolingual width of all molars with digital sliding calipers, and a variety of tibial parameters with peripheral quantitative computed tomography (pQCT) and a biomechanical testing apparatus. The landmark coordinates were analyzed for variation in size, shape, and fluctuating asymmetry (FA) using MorphoJ software, showing no effects on cranial size, on FA in females only (i.e., decreased asymmetry), and on shape in both sexes (i.e., decreased facial length and shift in the palatal suture). In the maxillary teeth, females in the highest dose group showed a significant decrease of 0.1 mm (p = 0.033) of the second molar only, whereas males in most dose groups showed average increases of 0.1 mm (p = 0.006–0.044) in all three molars. In the mandibular teeth, the only significant response to PCB 180 exposure was the average increase of 0.1 mm (p = 0.001–0.025) in the third molars of males only. Males also shower greater sensitivity in postcranial effects of increased tibial length and decreased cortical bone mass density, although only females showed significant effects on tibial bone area and thickness. These results demonstrate marked sex differences in effects of PCB 180, which can be attributed to differences in their underlying biological mechanisms of toxicity. Furthermore, although tooth and bone development are targets of both DL and NDL compounds, this study shows that there are marked differences in their mechanisms and effects. PMID:28957439

Skeletal and dental effects on rats following in utero/lactational exposure to the non-dioxin-like polychlorinated biphenyl PCB 180.

PubMed

Romero, Ashly N; Herlin, Maria; Finnilä, Mikko; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti; Sholts, Sabrina B

2017-01-01

Polychlorinated biphenyls (PCBs) are a large class of persistent organic pollutants that are potentially harmful to human and wildlife health. Although a small number of dioxin-like (DL) PCBs are well characterized, the majority of PCBs have non-dioxin-like (NDL) modes of action and biological effects that are less understood. We conducted a dose-response study of the skeletal and dental effects of in utero/lactational exposure to 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180), a NDL PCB congener that is abundantly present in the environment and foods, including mother's milk. In a sample of 35- and 84-day-old male and female offspring from pregnant rats exposed to different doses of PCB 180 (0, 10, 30, 100, 300, and 1000 mg/kg bw), we measured the three-dimensional (3D) coordinates of 27 landmarks on the craniofacial skeleton with a Microscribe G2X system, the buccolingual width of all molars with digital sliding calipers, and a variety of tibial parameters with peripheral quantitative computed tomography (pQCT) and a biomechanical testing apparatus. The landmark coordinates were analyzed for variation in size, shape, and fluctuating asymmetry (FA) using MorphoJ software, showing no effects on cranial size, on FA in females only (i.e., decreased asymmetry), and on shape in both sexes (i.e., decreased facial length and shift in the palatal suture). In the maxillary teeth, females in the highest dose group showed a significant decrease of 0.1 mm (p = 0.033) of the second molar only, whereas males in most dose groups showed average increases of 0.1 mm (p = 0.006-0.044) in all three molars. In the mandibular teeth, the only significant response to PCB 180 exposure was the average increase of 0.1 mm (p = 0.001-0.025) in the third molars of males only. Males also shower greater sensitivity in postcranial effects of increased tibial length and decreased cortical bone mass density, although only females showed significant effects on tibial bone area and thickness. These results demonstrate marked sex differences in effects of PCB 180, which can be attributed to differences in their underlying biological mechanisms of toxicity. Furthermore, although tooth and bone development are targets of both DL and NDL compounds, this study shows that there are marked differences in their mechanisms and effects.

Bone loss during partial weight bearing (1/6th gravity) is mitigated by resistance and aerobic exercise in mice

NASA Astrophysics Data System (ADS)

Boudreaux, R. D.; Metzger, C. E.; Macias, B. R.; Shirazi-Fard, Y.; Hogan, H. A.; Bloomfield, S. A.

2014-06-01

Astronauts on long duration missions continue to experience bone loss, as much as 1-2% each month, for up to 4.5 years after a mission. Mechanical loading of bone with exercise has been shown to increase bone formation, mass, and geometry. The aim of this study was to compare the efficacy of two exercise protocols during a period of reduced gravitational loading (1/6th body weight) in mice. Since muscle contractions via resistance exercise impart the largest physiological loads on the skeleton, we hypothesized that resistance training (via vertical tower climbing) would better protect against the deleterious musculoskeletal effects of reduced gravitational weight bearing when compared to endurance exercise (treadmill running). Young adult female BALB/cBYJ mice were randomly assigned to three groups: 1/6 g (G/6; n=6), 1/6 g with treadmill running (G/6+RUN; n=8), or 1/6 g with vertical tower climbing (G/6+CLB; n=9). Exercise was performed five times per week. Reduced weight bearing for 21 days was achieved through a novel harness suspension system. Treadmill velocity (12-20 m/min) and daily run time duration (32-51 min) increased incrementally throughout the study. Bone geometry and volumetric bone mineral density (vBMD) at proximal metaphysis and mid-diaphysis tibia were assessed by in vivo peripheral quantitative computed tomography (pQCT) on days 0 and 21 and standard dynamic histomorphometry was performed on undemineralized sections of the mid-diaphysis after tissue harvest. G/6 caused a significant decrease (P<0.001) in proximal tibia metaphysis total vBMD (-9.6%). These reductions of tibia metaphyseal vBMD in G/6 mice were mitigated in both G/6+RUN and G/6+CLB groups (P<0.05). After 21 days of G/6, we saw an absolute increase in tibia mid-diaphysis vBMD and in distal metaphysis femur vBMD in both G/6+RUN and G/6+CLB mice (P<0.05). Substantial increases in endocortical and periosteal mineralizing surface (MS/BS) at mid-diaphysis tibia in G/6+CLB demonstrate that bone formation can be increased even in the presence of reduced weight bearing. These data suggest that moderately vigorous endurance exercise and resistance training, through treadmill running or climb training mitigates decrements in vBMD during 21 days of reduced weight bearing. Consistent with our hypothesis, tower climb training, most pronounced in the tibia mid-diaphysis, provides a more potent osteogenic response compared to treadmill running.

Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

PubMed Central

Zhang, Jian; Lazarenko, Oxana P.; Kang, Jie; Blackburn, Michael L.; Ronis, Martin J. J.; Badger, Thomas M.; Chen, Jin-Ran

2013-01-01

Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia, demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ) which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption. PMID:23936431

Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains

PubMed Central

Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2008-01-01

Because particular inbred strains of experimental animals are informative for only a subset of the genes underlying variability in BMD, we undertook a genome screen to identify quantitative trait loci (QTLs) in 828 F2 progeny (405 males and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA) strains of rats. This screen was performed to complement our study in female Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors underlying the complex genetic architecture of BMD in the rat model. Microsatellite genotyping was performed using markers at an average density of 20 cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl software to detect QTLs acting in both sexes as well as those having sex-specific effects. A QTL was detected in both sexes on chromosome 18 for midfemur volumetric BMD (vBMD; genome-wide, p < 0.01). On distal chromosome 1, a QTL was found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also detected. These included a male-specific QTL (p < 0.01) on chromosome 8 and a female-specific QTL on chromosomes 7 and 14 (p < 0.01). Few of the QTLs identified showed overlap with the significant QTLs from the F344/LEW cross. These results confirm that the genetic influence on BMD in the rat model is quite complex and would seem to be influenced by a number of different genes, some of which have sex-specific effects. PMID:18707222

Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL).

PubMed

Kaste, S C; Qi, A; Smith, K; Surprise, H; Lovorn, E; Boyett, J; Ferry, R J; Relling, M V; Shurtleff, S A; Pui, C H; Carbone, L; Hudson, M M; Ness, K K

2014-05-01

We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78). Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). © 2014 Wiley Periodicals, Inc.

Computer simulation of the metastatic progression.

PubMed

Wedemann, Gero; Bethge, Anja; Haustein, Volker; Schumacher, Udo

2014-01-01

A novel computer model based on a discrete event simulation procedure describes quantitatively the processes underlying the metastatic cascade. Analytical functions describe the size of the primary tumor and the metastases, while a rate function models the intravasation events of the primary tumor and metastases. Events describe the behavior of the malignant cells until the formation of new metastases. The results of the computer simulations are in quantitative agreement with clinical data determined from a patient with hepatocellular carcinoma in the liver. The model provides a more detailed view on the process than a conventional mathematical model. In particular, the implications of interventions on metastasis formation can be calculated.

Combining Ultrasound Pulse-Echo and Transmission Computed Tomography for Quantitative Imaging the Cortical Shell of Long Bone Replicas

NASA Astrophysics Data System (ADS)

Shortell, Matthew P.; Althomali, Marwan A. M.; Wille, Marie-Luise; Langton, Christian M.

2017-11-01

We demonstrate a simple technique for quantitative ultrasound imaging of the cortical shell of long bone replicas. Traditional ultrasound computed tomography instruments use the transmitted or reflected waves for separate reconstructions but suffer from strong refraction artefacts in highly heterogenous samples such as bones in soft tissue. The technique described here simplifies the long bone to a two-component composite and uses both the transmitted and reflected waves for reconstructions, allowing the speed of sound and thickness of the cortical shell to be calculated accurately. The technique is simple to implement, computationally inexpensive and sample positioning errors are minimal.

Qualitative and quantitative interpretation of SEM image using digital image processing.

PubMed

Saladra, Dawid; Kopernik, Magdalena

2016-10-01

The aim of the this study is improvement of qualitative and quantitative analysis of scanning electron microscope micrographs by development of computer program, which enables automatic crack analysis of scanning electron microscopy (SEM) micrographs. Micromechanical tests of pneumatic ventricular assist devices result in a large number of micrographs. Therefore, the analysis must be automatic. Tests for athrombogenic titanium nitride/gold coatings deposited on polymeric substrates (Bionate II) are performed. These tests include microshear, microtension and fatigue analysis. Anisotropic surface defects observed in the SEM micrographs require support for qualitative and quantitative interpretation. Improvement of qualitative analysis of scanning electron microscope images was achieved by a set of computational tools that includes binarization, simplified expanding, expanding, simple image statistic thresholding, the filters Laplacian 1, and Laplacian 2, Otsu and reverse binarization. Several modifications of the known image processing techniques and combinations of the selected image processing techniques were applied. The introduced quantitative analysis of digital scanning electron microscope images enables computation of stereological parameters such as area, crack angle, crack length, and total crack length per unit area. This study also compares the functionality of the developed computer program of digital image processing with existing applications. The described pre- and postprocessing may be helpful in scanning electron microscopy and transmission electron microscopy surface investigations. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

[The development of a computer model in the quantitative assessment of thallium-201 myocardial scintigraphy].

PubMed

Raineri, M; Traina, M; Rotolo, A; Candela, B; Lombardo, R M; Raineri, A A

1993-05-01

Thallium-201 scintigraphy is a widely used noninvasive procedure for the detection and prognostic assessment of patients with suspected or proven coronary artery disease. Thallium uptake can be evaluated by a visual analysis or by a quantitative interpretation. Quantitative scintigraphy enhances disease detection in individual coronary arteries, provides a more precise estimate of the amount of ischemic myocardium, distinguishing scar from hypoperfused tissue. Due to the great deal of data, analysis, interpretation and comparison of thallium uptake can be very complex. We designed a computer-based system for the interpretation of quantitative thallium-201 scintigraphy data uptake. We used a database (DataEase 4.2-DataEase Italia). Our software has the following functions: data storage; calculation; conversion of numerical data into different definitions classifying myocardial perfusion; uptake data comparison; automatic conclusion; comparison of different scintigrams for the same patient. Our software is made up by 4 sections: numeric analysis, descriptive analysis, automatic conclusion, clinical remarks. We introduced in the computer system appropriate information, "logical paths", that use the "IF ... THEN" rules. The software executes these rules in order to analyze the myocardial regions in the 3 phases of scintigraphic analysis (stress, redistribution, re-injection), in the 3 projections (LAO 45 degrees, LAT,ANT), considering our uptake cutoff, obtaining, finally, the automatic conclusions. For these reasons, our computer-based system could be considered a real "expert system".

Cluster-continuum quasichemical theory calculation of the lithium ion solvation in water, acetonitrile and dimethyl sulfoxide: an absolute single-ion solvation free energy scale.

PubMed

Carvalho, Nathalia F; Pliego, Josefredo R

2015-10-28

Absolute single-ion solvation free energy is a very useful property for understanding solution phase chemistry. The real solvation free energy of an ion depends on its interaction with the solvent molecules and on the net potential inside the solute cavity. The tetraphenyl arsonium-tetraphenyl borate (TATB) assumption as well as the cluster-continuum quasichemical theory (CC-QCT) approach for Li(+) solvation allows access to a solvation scale excluding the net potential. We have determined this free energy scale investigating the solvation of the lithium ion in water (H2O), acetonitrile (CH3CN) and dimethyl sulfoxide (DMSO) solvents via the CC-QCT approach. Our calculations at the MP2 and MP4 levels with basis sets up to the QZVPP+diff quality, and including solvation of the clusters and solvent molecules by the dielectric continuum SMD method, predict the solvation free energy of Li(+) as -116.1, -120.6 and -123.6 kcal mol(-1) in H2O, CH3CN and DMSO solvents, respectively (1 mol L(-1) standard state). These values are compatible with the solvation free energy of the proton of -253.4, -253.2 and -261.1 kcal mol(-1) in H2O, CH3CN and DMSO solvents, respectively. Deviations from the experimental TATB scale are only 1.3 kcal mol(-1) in H2O and 1.8 kcal mol(-1) in DMSO solvents. However, in the case of CH3CN, the deviation reaches a value of 9.2 kcal mol(-1). The present study suggests that the experimental TATB scale is inconsistent for CH3CN. A total of 125 values of the solvation free energy of ions in these three solvents were obtained. These new data should be useful for the development of theoretical solvation models.

Ethnic differences in bone geometry between White, Black and South Asian men in the UK.

PubMed

Zengin, A; Pye, S R; Cook, M J; Adams, J E; Wu, F C W; O'Neill, T W; Ward, K A

2016-10-01

Relatively little is known about the bone health of ethnic groups within the UK and data are largely restricted to women. The aim of this study was to investigate ethnic differences in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), bone geometry and strength in UK men. White European, Black Afro-Caribbean and South Asian men aged over 40years were recruited from Greater Manchester, UK. aBMD at the spine, hip, femoral neck and whole body were measured by DXA. Bone geometry, strength and vBMD were measured at the radius and tibia using pQCT at the metaphysis (4%) and diaphysis (50% radius; 38% tibia) sites. Adjustments were made for age, weight and height. Black men had higher aBMD at the whole body, total hip and femoral neck compared to White and South Asian men independent of body size adjustments, with no differences between the latter two groups. White men had longer hip axis lengths than both Black and South Asian men. There were fewer differences in vBMD but White men had significantly lower cortical vBMD at the tibial diaphysis than Black and South Asian men (p<0.001). At the tibia and radius diaphysis, Black men had larger bones with thicker cortices and greater bending strength than the other groups. There were fewer differences between White and South Asian men. At the metaphysis, South Asian men had smaller bones (p=0.02) and lower trabecular vBMD at the tibia (p=0.003). At the diaphysis, after size-correction, South Asian men had similar sized bones but thinner cortices than White men; measures of strength were not broadly reduced in the South Asian men. Combining pQCT and DXA measurements has given insight into differences in bone phenotype in men from different ethnic backgrounds. Understanding such differences is important in understanding the aetiology of male osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Is the gas-phase OH+H2CO reaction a source of HCO in interstellar cold dark clouds? A kinetic, dynamic and modelling study

PubMed Central

Ocaña, A. J.; Jiménez, E.; Ballesteros, B.; Canosa, A.; Antiñolo, M.; Albaladejo, J.; Agúndez, M.; Cernicharo, J.; Zanchet, A.; del Mazo, P.; Roncero, O.; Aguado, A.

2018-01-01

Chemical kinetics of neutral-neutral gas-phase reactions at ultralow temperatures is a fascinating research subject with important implications on the chemistry of complex organic molecules in the interstellar medium (T∼10-100K). Scarce kinetic information is currently available for this kind of reactions at T<200 K. In this work we use the CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme, which means Reaction Kinetics in a Uniform Supersonic Flow) technique to measure for the first time the rate coefficients (k) of the gas-phase OH+H2CO reaction between 22 and 107 K. k values greatly increase from 2.1×10-11 cm3 s-1 at 107 K to 1.2×10-10 cm3 s-1 at 22 K. This is also confirmed by quasi-classical trajectories (QCT) at collision energies down to 0.1 meV performed using a new full dimension and ab initio potential energy surface, recently developed which generates highly accurate potential and includes long range dipole-dipole interactions. QCT calculations indicate that at low temperatures HCO is the exclusive product for the OH+H2CO reaction. In order to revisit the chemistry of HCO in cold dense clouds, k is reasonably extrapolated from the experimental results at 10K (2.6×10-10 cm3 s-1). The modeled abundances of HCO are in agreement with the observations in cold dark clouds for an evolving time of 105-106 yrs. The different sources of production of HCO are presented and the uncertainties in the chemical networks discussed. This reaction can be expected to be a competitive process in the chemistry of prestellar cores. The present reaction is shown to account for a few percent of the total HCO production rate. Extensions to photodissociation regions and diffuse clouds environments are also commented. PMID:29880977

Is the Gas-phase OH+H2CO Reaction a Source of HCO in Interstellar Cold Dark Clouds? A Kinetic, Dynamic, and Modeling Study

NASA Astrophysics Data System (ADS)

Ocaña, A. J.; Jiménez, E.; Ballesteros, B.; Canosa, A.; Antiñolo, M.; Albaladejo, J.; Agúndez, M.; Cernicharo, J.; Zanchet, A.; del Mazo, P.; Roncero, O.; Aguado, A.

2017-11-01

The chemical kinetics of neutral-neutral gas-phase reactions at ultralow temperatures is a fascinating research subject with important implications on the chemistry of complex organic molecules in the interstellar medium (T ˜ 10-100 K). Scarce kinetic information is currently available for these kinds of reactions at T < 200 K. In this work, we use the Cinétique de Réaction en Ecoulement Supersonique Uniforme (CRESU; Reaction Kinetics in a Uniform Supersonic Flow) technique to measure for the first time the rate coefficients (k) of the gas-phase OH+H2CO reaction between 22 and 107 K. The k values greatly increase from 2.1 × 10-11 cm3 s-1 at 107 K to 1.2 × 10-10 cm3 s-1 at 22 K. This is also confirmed by quasi-classical trajectories (QCT) at collision energies down to 0.1 meV performed using a new full dimension and ab initio potential energy surface that generates highly accurate potential and includes long-range dipole-dipole interactions. QCT calculations indicate that at low temperatures HCO is the exclusive product for the OH+H2CO reaction. In order to revisit the chemistry of HCO in cold dense clouds, k is reasonably extrapolated from the experimental results at 10 K (2.6 × 10-10 cm3 s-1). The modeled abundances of HCO are in agreement with the observations in cold dark clouds for an evolving time of 105-106 yr. The different sources of production of HCO are presented and the uncertainties in the chemical networks are discussed. The present reaction is shown to account for a few percent of the total HCO production rate. This reaction can be expected to be a competitive process in the chemistry of prestellar cores. Extensions to photodissociation regions and diffuse cloud environments are also addressed.

Is the gas-phase OH+H2CO reaction a source of HCO in interstellar cold dark clouds? A kinetic, dynamic and modelling study.

PubMed

Ocaña, A J; Jiménez, E; Ballesteros, B; Canosa, A; Antiñolo, M; Albaladejo, J; Agúndez, M; Cernicharo, J; Zanchet, A; Del Mazo, P; Roncero, O; Aguado, A

2017-11-20

Chemical kinetics of neutral-neutral gas-phase reactions at ultralow temperatures is a fascinating research subject with important implications on the chemistry of complex organic molecules in the interstellar medium (T∼10-100K). Scarce kinetic information is currently available for this kind of reactions at T<200 K. In this work we use the CRESU ( Cinétique de Réaction en Ecoulement Supersonique Uniforme , which means Reaction Kinetics in a Uniform Supersonic Flow) technique to measure for the first time the rate coefficients ( k ) of the gas-phase OH+H 2 CO reaction between 22 and 107 K. k values greatly increase from 2.1×10 -11 cm 3 s -1 at 107 K to 1.2×10 -10 cm 3 s -1 at 22 K. This is also confirmed by quasi-classical trajectories (QCT) at collision energies down to 0.1 meV performed using a new full dimension and ab initio potential energy surface, recently developed which generates highly accurate potential and includes long range dipole-dipole interactions. QCT calculations indicate that at low temperatures HCO is the exclusive product for the OH+H 2 CO reaction. In order to revisit the chemistry of HCO in cold dense clouds, k is reasonably extrapolated from the experimental results at 10K (2.6×10 -10 cm 3 s -1 ). The modeled abundances of HCO are in agreement with the observations in cold dark clouds for an evolving time of 10 5 -10 6 yrs. The different sources of production of HCO are presented and the uncertainties in the chemical networks discussed. This reaction can be expected to be a competitive process in the chemistry of prestellar cores. The present reaction is shown to account for a few percent of the total HCO production rate. Extensions to photodissociation regions and diffuse clouds environments are also commented.

Relative contributions of neutral and non-neutral processes to clinal variation in calyx lobe length in the series Sakawanum (Asarum: Aristolochiaceae).

PubMed

Takahashi, Daiki; Teramine, Tsutomu; Sakaguchi, Shota; Setoguchi, Hiroaki

2018-01-25

Clines, the gradual variation in measurable traits along a geographical axis, play a major role in evolution and can contribute to our understanding of the relative roles of selective and neutral process in trait variation. Using genetic and morphological analyses, the relative contributions of neutral and non-neutral processes were explored to infer the evolutionary history of species of the series Sakawanum (genus Asarum), which shows significant clinal variation in calyx lobe length. A total of 27 populations covering the natural geographical distribution of the series Sakawanum were sampled. Six nuclear microsatellite markers were used to investigate genetic structure and genetic diversity. The lengths of calyx lobes of multiple populations were measured to quantify their geographical and taxonomic differentiation. To detect the potential impact of selective pressure, morphological differentiation was compared with genetic differentiation (QCT-FST comparison). Average calyx lobe length of A. minamitanianum was 124.11 mm, while that of A. costatum was 13.80 mm. Though gradually changing along the geographical axis within series, calyx lobe lengths were significantly differentiated among the taxa. Genetic differentiation between taxa was low (FST = 0.099), but a significant geographical structure along the morphological cline was detected. Except for one taxon pair, pairwise QCT values were significantly higher than the neutral genetic measures of FST and G'ST. Divergent selection may have driven the calyx lobe length variation in series Sakawanum taxa, although the underlying mechanism is still not clear. The low genetic differentiation indicates recent divergence and/or gene flows between geographically close taxa. These neutral processes would also affect the clinal variation in calyx lobe lengths. Overall, this study implies the roles of population history and divergent selection in shaping the current cline of a flower trait in the series Sakawanum. © The Author(s) 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High risk of adrenal toxicity of N1-desoxy quinoxaline 1,4-dioxide derivatives and the protection of oligomeric proanthocyanidins (OPC) in the inhibition of the expression of aldosterone synthetase in H295R cells.

PubMed

Wang, Xu; Yang, Chunhui; Ihsan, Awais; Luo, Xun; Guo, Pu; Cheng, Guyue; Dai, Menghong; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

2016-02-03

Quinoxaline 1,4-dioxide derivatives (QdNOs) with a wide range of biological activities are used in animal husbandry worldwide. It was found that QdNOs significantly inhibited the gene expression of CYP11B1 and CYP11B2, the key aldosterone synthases, and thus reduced aldosterone levels. However, whether the metabolites of QdNOs have potential adrenal toxicity and the role of oxidative stress in the adrenal toxicity of QdNOs remains unclear. The relatively new QdNOs, cyadox (CYA), mequindox (MEQ), quinocetone (QCT) and their metabolites, were selected for elucidation of their toxic mechanisms in H295R cells. Interestingly, the results showed that the main toxic metabolites of QCT, MEQ, and CYA were their N1-desoxy metabolites, which were more harmful than other metabolites and evoked dose and time-dependent cell damage on adrenal cells and inhibited aldosterone production. Gene and protein expression of CYP11B1 and CYP11B2 and mRNA expression of transcription factors, such as NURR1, NGFIB, CREB, SF-1, and ATF-1, were down regulated by N1-desoxy QdNOs. The natural inhibitors of oxidant stress, oligomeric proanthocyanidins (OPC), could upregulate the expression of diverse transcription factors, including CYP11B1 and CYP11B2, and elevated aldosterone levels to reduce adrenal toxicity. This study demonstrated for the first time that N1-desoxy QdNOs have the potential to be the major toxic metabolites in adrenal toxicity, which may shed new light on the adrenal toxicity of these fascinating compounds and help to provide a basic foundation for the formulation of safety controls for animal products and the design of new QdNOs with less harmful effects. Copyright © 2016. Published by Elsevier Ireland Ltd.

Operator Variability in Scan Positioning is a Major Component of HR-pQCT Precision Error and is Reduced by Standardized Training

PubMed Central

Bonaretti, Serena; Vilayphiou, Nicolas; Chan, Caroline Mai; Yu, Andrew; Nishiyama, Kyle; Liu, Danmei; Boutroy, Stephanie; Ghasem-Zadeh, Ali; Boyd, Steven K.; Chapurlat, Roland; McKay, Heather; Shane, Elizabeth; Bouxsein, Mary L.; Black, Dennis M.; Majumdar, Sharmila; Orwoll, Eric S.; Lang, Thomas F.; Khosla, Sundeep; Burghardt, Andrew J.

2017-01-01

Introduction HR-pQCT is increasingly used to assess bone quality, fracture risk and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection (“scout view image”) and define the region to be scanned by positioning a “reference line” on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. Methods To evaluate the operator in vivo measurement precision we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner’s software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled 6 new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. Results In vivo precision errors were up to three-fold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. Inter-operator precision errors were significantly greater than short-term intra-operator precision (p<0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators, and lower inter-operator reproducibility (p<0.001). Precision errors were significantly greater for the radius than for the tibia. Conclusion Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online (http://webapps.radiology.ucsf.edu/refline/). PMID:27475931

Computer measurement of arterial disease

NASA Technical Reports Server (NTRS)

Armstrong, J.; Selzer, R. H.; Barndt, R.; Blankenhorn, D. H.; Brooks, S.

1980-01-01

Image processing technique quantifies human atherosclerosis by computer analysis of arterial angiograms. X-ray film images are scanned and digitized, arterial shadow is tracked, and several quantitative measures of lumen irregularity are computed. In other tests, excellent agreement was found between computer evaluation of femoral angiograms on living subjects and evaluation by teams of trained angiographers.

Computational Algorithmization: Limitations in Problem Solving Skills in Computational Sciences Majors at University of Oriente

ERIC Educational Resources Information Center

Castillo, Antonio S.; Berenguer, Isabel A.; Sánchez, Alexander G.; Álvarez, Tomás R. R.

2017-01-01

This paper analyzes the results of a diagnostic study carried out with second year students of the computational sciences majors at University of Oriente, Cuba, to determine the limitations that they present in computational algorithmization. An exploratory research was developed using quantitative and qualitative methods. The results allowed…

ADVANCED COMPUTATIONAL METHODS IN DOSE MODELING

EPA Science Inventory

The overall goal of the EPA-ORD NERL research program on Computational Toxicology (CompTox) is to provide the Agency with the tools of modern chemistry, biology, and computing to improve quantitative risk assessments and reduce uncertainties in the source-to-adverse outcome conti...

Does Homework Really Matter for College Students in Quantitatively-Based Courses?

ERIC Educational Resources Information Center

Young, Nichole; Dollman, Amanda; Angel, N. Faye

2016-01-01

This investigation was initiated by two students in an Advanced Computer Applications course. They sought to examine the influence of graded homework on final grades in quantitatively-based business courses. They were provided with data from three quantitatively-based core business courses over a period of five years for a total of 10 semesters of…

A Text Analysis of the Marine Corps Fitness Report

DTIC Science & Technology

2017-06-01

difficulty in quantitatively analyzing textual. The study pulls 835 anonymous and non-attributable surveys between 2005 and 2009 from the Center for... quantitative assessments of performance. 14. SUBJECT TERMS natural language processing, fitness reports, computational linguistics, manpower 15. NUMBER...Corps provide word-picture guidance to distinguish talented Marines and promote conformity in issuing quantitative assessments of performance. vi

Quantitative ROESY analysis of computational models: structural studies of citalopram and β-cyclodextrin complexes by (1) H-NMR and computational methods.

PubMed

Ali, Syed Mashhood; Shamim, Shazia

2015-07-01

Complexation of racemic citalopram with β-cyclodextrin (β-CD) in aqueous medium was investigated to determine atom-accurate structure of the inclusion complexes. (1) H-NMR chemical shift change data of β-CD cavity protons in the presence of citalopram confirmed the formation of 1 : 1 inclusion complexes. ROESY spectrum confirmed the presence of aromatic ring in the β-CD cavity but whether one of the two or both rings was not clear. Molecular mechanics and molecular dynamic calculations showed the entry of fluoro-ring from wider side of β-CD cavity as the most favored mode of inclusion. Minimum energy computational models were analyzed for their accuracy in atomic coordinates by comparison of calculated and experimental intermolecular ROESY peak intensities, which were not found in agreement. Several least energy computational models were refined and analyzed till calculated and experimental intensities were compatible. The results demonstrate that computational models of CD complexes need to be analyzed for atom-accuracy and quantitative ROESY analysis is a promising method. Moreover, the study also validates that the quantitative use of ROESY is feasible even with longer mixing times if peak intensity ratios instead of absolute intensities are used. Copyright © 2015 John Wiley & Sons, Ltd.

A method for evaluating the murine pulmonary vasculature using micro-computed tomography.

PubMed

Phillips, Michael R; Moore, Scott M; Shah, Mansi; Lee, Clara; Lee, Yueh Z; Faber, James E; McLean, Sean E

2017-01-01

Significant mortality and morbidity are associated with alterations in the pulmonary vasculature. While techniques have been described for quantitative morphometry of whole-lung arterial trees in larger animals, no methods have been described in mice. We report a method for the quantitative assessment of murine pulmonary arterial vasculature using high-resolution computed tomography scanning. Mice were harvested at 2 weeks, 4 weeks, and 3 months of age. The pulmonary artery vascular tree was pressure perfused to maximal dilation with a radio-opaque casting material with viscosity and pressure set to prevent capillary transit and venous filling. The lungs were fixed and scanned on a specimen computed tomography scanner at 8-μm resolution, and the vessels were segmented. Vessels were grouped into categories based on lumen diameter and branch generation. Robust high-resolution segmentation was achieved, permitting detailed quantitation of pulmonary vascular morphometrics. As expected, postnatal lung development was associated with progressive increase in small-vessel number and arterial branching complexity. These methods for quantitative analysis of the pulmonary vasculature in postnatal and adult mice provide a useful tool for the evaluation of mouse models of disease that affect the pulmonary vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

Leaf epidermis images for robust identification of plants

PubMed Central

da Silva, Núbia Rosa; Oliveira, Marcos William da Silva; Filho, Humberto Antunes de Almeida; Pinheiro, Luiz Felipe Souza; Rossatto, Davi Rodrigo; Kolb, Rosana Marta; Bruno, Odemir Martinez

2016-01-01

This paper proposes a methodology for plant analysis and identification based on extracting texture features from microscopic images of leaf epidermis. All the experiments were carried out using 32 plant species with 309 epidermal samples captured by an optical microscope coupled to a digital camera. The results of the computational methods using texture features were compared to the conventional approach, where quantitative measurements of stomatal traits (density, length and width) were manually obtained. Epidermis image classification using texture has achieved a success rate of over 96%, while success rate was around 60% for quantitative measurements taken manually. Furthermore, we verified the robustness of our method accounting for natural phenotypic plasticity of stomata, analysing samples from the same species grown in different environments. Texture methods were robust even when considering phenotypic plasticity of stomatal traits with a decrease of 20% in the success rate, as quantitative measurements proved to be fully sensitive with a decrease of 77%. Results from the comparison between the computational approach and the conventional quantitative measurements lead us to discover how computational systems are advantageous and promising in terms of solving problems related to Botany, such as species identification. PMID:27217018

Mapping Quantitative Traits in Unselected Families: Algorithms and Examples

PubMed Central

Dupuis, Josée; Shi, Jianxin; Manning, Alisa K.; Benjamin, Emelia J.; Meigs, James B.; Cupples, L. Adrienne; Siegmund, David

2009-01-01

Linkage analysis has been widely used to identify from family data genetic variants influencing quantitative traits. Common approaches have both strengths and limitations. Likelihood ratio tests typically computed in variance component analysis can accommodate large families but are highly sensitive to departure from normality assumptions. Regression-based approaches are more robust but their use has primarily been restricted to nuclear families. In this paper, we develop methods for mapping quantitative traits in moderately large pedigrees. Our methods are based on the score statistic which in contrast to the likelihood ratio statistic, can use nonparametric estimators of variability to achieve robustness of the false positive rate against departures from the hypothesized phenotypic model. Because the score statistic is easier to calculate than the likelihood ratio statistic, our basic mapping methods utilize relatively simple computer code that performs statistical analysis on output from any program that computes estimates of identity-by-descent. This simplicity also permits development and evaluation of methods to deal with multivariate and ordinal phenotypes, and with gene-gene and gene-environment interaction. We demonstrate our methods on simulated data and on fasting insulin, a quantitative trait measured in the Framingham Heart Study. PMID:19278016

Computational Skills for Biology Students

ERIC Educational Resources Information Center

Gross, Louis J.

2008-01-01

This interview with Distinguished Science Award recipient Louis J. Gross highlights essential computational skills for modern biology, including: (1) teaching concepts listed in the Math & Bio 2010 report; (2) illustrating to students that jobs today require quantitative skills; and (3) resources and materials that focus on computational skills.

Quantitative Modeling of Earth Surface Processes

NASA Astrophysics Data System (ADS)

Pelletier, Jon D.

This textbook describes some of the most effective and straightforward quantitative techniques for modeling Earth surface processes. By emphasizing a core set of equations and solution techniques, the book presents state-of-the-art models currently employed in Earth surface process research, as well as a set of simple but practical research tools. Detailed case studies demonstrate application of the methods to a wide variety of processes including hillslope, fluvial, aeolian, glacial, tectonic, and climatic systems. Exercises at the end of each chapter begin with simple calculations and then progress to more sophisticated problems that require computer programming. All the necessary computer codes are available online at www.cambridge.org/9780521855976. Assuming some knowledge of calculus and basic programming experience, this quantitative textbook is designed for advanced geomorphology courses and as a reference book for professional researchers in Earth and planetary science looking for a quantitative approach to Earth surface processes.

A Quantitative Geochemical Target for Modeling the Formation of the Earth and Moon

NASA Technical Reports Server (NTRS)

Boyce, Jeremy W.; Barnes, Jessica J.; McCubbin, Francis M.

2017-01-01

The past decade has been one of geochemical, isotopic, and computational advances that are bringing the laboratory measurements and computational modeling neighborhoods of the Earth-Moon community to ever closer proximity. We are now however in the position to become even better neighbors: modelers can generate testable hypthotheses for geochemists; and geochemists can provide quantitive targets for modelers. Here we present a robust example of the latter based on Cl isotope measurements of mare basalts.

Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

PubMed Central

Kim, Hyun Joo; Bang, Ji-In; Kim, Ji-Young; Moon, Jae Hoon; So, Young

2017-01-01

Objective Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. Materials and Methods A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of 99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. Results GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). Conclusion A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients. PMID:28458607

Quantitative collision induced mass spectrometry of substituted piperazines - A correlative analysis between theory and experiment

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka; Spiteller, Michael

2017-12-01

The present paper deals with quantitative kinetics and thermodynamics of collision induced dissociation (CID) reactions of piperazines under different experimental conditions together with a systematic description of effect of counter-ions on common MS fragment reactions of piperazines; and intra-molecular effect of quaternary cyclization of substituted piperazines yielding to quaternary salts. There are discussed quantitative model equations of rate constants as well as free Gibbs energies of series of m-independent CID fragment processes in GP, which have been evidenced experimentally. Both kinetic and thermodynamic parameters are also predicted by computational density functional theory (DFT) and ab initio both static and dynamic methods. The paper examines validity of Maxwell-Boltzmann distribution to non-Boltzmann CID processes in quantitatively as well. The experiments conducted within the latter framework yield to an excellent correspondence with theoretical quantum chemical modeling. The important property of presented model equations of reaction kinetics is the applicability in predicting unknown and assigning of known mass spectrometric (MS) patterns. The nature of "GP" continuum of CID-MS coupled scheme of measurements with electrospray ionization (ESI) source is discussed, performing parallel computations in gas-phase (GP) and polar continuum at different temperatures and ionic strengths. The effect of pressure is presented. The study contributes significantly to methodological and phenomenological developments of CID-MS and its analytical implementations for quantitative and structural analyses. It also demonstrates great prospective of a complementary application of experimental CID-MS and computational quantum chemistry studying chemical reactivity, among others. To a considerable extend this work underlies the place of computational quantum chemistry to the field of experimental analytical chemistry in particular highlighting the structural analysis.

Use of quantitative SPECT/CT reconstruction in 99mTc-sestamibi imaging of patients with renal masses.

PubMed

Jones, Krystyna M; Solnes, Lilja B; Rowe, Steven P; Gorin, Michael A; Sheikhbahaei, Sara; Fung, George; Frey, Eric C; Allaf, Mohamad E; Du, Yong; Javadi, Mehrbod S

2018-02-01

Technetium-99m ( 99m Tc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99m Tc-sestamibi. Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions. The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions. Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99m Tc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions.

Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?

NASA Technical Reports Server (NTRS)

Sibonga, Jean

2008-01-01

The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

Quantitative Predictive Models for Systemic Toxicity (SOT)

EPA Science Inventory

Models to identify systemic and specific target organ toxicity were developed to help transition the field of toxicology towards computational models. By leveraging multiple data sources to incorporate read-across and machine learning approaches, a quantitative model of systemic ...

Quantitative Evaluation of a Planetary Renderer for Terrain Relative Navigation

NASA Astrophysics Data System (ADS)

Amoroso, E.; Jones, H.; Otten, N.; Wettergreen, D.; Whittaker, W.

2016-11-01

A ray-tracing computer renderer tool is presented based on LOLA and LROC elevation models and is quantitatively compared to LRO WAC and NAC images for photometric accuracy. We investigated using rendered images for terrain relative navigation.

Medical privacy protection based on granular computing.

PubMed

Wang, Da-Wei; Liau, Churn-Jung; Hsu, Tsan-Sheng

2004-10-01

Based on granular computing methodology, we propose two criteria to quantitatively measure privacy invasion. The total cost criterion measures the effort needed for a data recipient to find private information. The average benefit criterion measures the benefit a data recipient obtains when he received the released data. These two criteria remedy the inadequacy of the deterministic privacy formulation proposed in Proceedings of Asia Pacific Medical Informatics Conference, 2000; Int J Med Inform 2003;71:17-23. Granular computing methodology provides a unified framework for these quantitative measurements and previous bin size and logical approaches. These two new criteria are implemented in a prototype system Cellsecu 2.0. Preliminary system performance evaluation is conducted and reviewed.

Computation of the three-dimensional medial surface dynamics of the vocal folds.

PubMed

Döllinger, Michael; Berry, David A

2006-01-01

To increase our understanding of pathological and healthy voice production, quantitative measurement of the medial surface dynamics of the vocal folds is significant, albeit rarely performed because of the inaccessibility of the vocal folds. Using an excised hemilarynx methodology, a new calibration technique, herein referred to as the linear approximate (LA) method, was introduced to compute the three-dimensional coordinates of fleshpoints along the entire medial surface of the vocal fold. The results were compared with results from the direct linear transform. An associated error estimation was presented, demonstrating the improved accuracy of the new method. A test on real data was reported including computation of quantitative measurements of vocal fold dynamics.