Reference values and clinical predictors of bone strength for HR-pQCT-based distal radius and tibia strength assessments in women and men.

Reference values for radius and tibia strength using multiple-stack high-resolution peripheral quantitative computed tomography (HR-pQCT) with homogenized finite element analysis are presented in order to derive critical values improving risk prediction models of osteoporosis. Gender and femoral neck areal bone mineral density (aBMD) were independent predictors of bone strength. INTRODUCTION The purpose was to obtain reference values for radius and tibia bone strength computed by using the homogenized finite element analysis (hFE) using multiple stacks with a HR-pQCT. METHODS Male and female healthy participants aged 20-39 years were recruited at the University Hospital of Bern. They underwent interview and clinical examination including hand grip, gait speed and DXA of the hip. The nondominant forearm and tibia were scanned with a double and a triple-stack protocol, respectively, using HR-pQCT (XCT II, SCANCO Medical AG). Bone strength was estimated by using the hFE analysis, and reference values were calculated using quantile regression. Multivariable analyses were performed to identify clinical predictors of bone strength. RESULTS Overall, 46 women and 41 men were recruited with mean ages of 25.1 (sd 5.0) and 26.2 (sd 5.2) years. Sex-specific reference values for bone strength were established. Men had significantly higher strength for radius (mean (sd) 6640 (1800) N vs. 4110 (1200) N; p < 0.001) and tibia (18,200 (4220) N vs. 11,970 (3150) N; p < 0.001) than women. In the two multivariable regression models with and without total hip aBMD, the addition of neck hip aBMD significantly improved the model (p < 0.001). No clinical predictors of bone strength other than gender and aBMD were identified. CONCLUSION Reference values for radius and tibia strength using multiple HR-pQCT stacks with hFE analysis are presented and provide the basis to help refining accurate risk prediction models. Femoral neck aBMD and gender were significant predictors of bone strength

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients

Recruitment of lateral rostral prefrontal cortex in spontaneous and task-related thoughts

Behavioural and neuroimaging studies suggest that spontaneous and task-related thought processes share common cognitive mechanisms and neural bases. Lateral rostral prefrontal cortex (RPFC) is a brain region that has been implicated both in spontaneous thought and in high-level cognitive control processes, such as goal/subgoal integration and the manipulation of self-generated thoughts. We therefore propose that the recruitment of lateral RPFC may follow a U-shaped function of cognitive demand: relatively high in low-demand situations conducive to the emergence of spontaneous thought, and in high-demand situations depending on processes supported by this brain region. We used functional magnetic resonance imaging to investigate brain activity while healthy participants performed two tasks, each with three levels of cognitive demands, in a block design. The frequency of task-unrelated thoughts, measured by questionnaire, was highest in the low cognitive demand condition. Low and high cognitive demand conditions were each compared to the intermediate level. Lateral RPFC and superior parietal cortex were recruited in both comparisons, with additional activations specific to each contrast. These results suggest that RPFC is involved both when (a) task demands are low, and the mind wanders, and (b) the task requires goal/subgoal integration and manipulation of self-generated thoughts

New Suggestions for the Mechanical Control of Bone Remodeling

Bone is constantly renewed over our lifetime through the process of bone (re)modeling. This process is important for bone to allow it to adapt to its mechanical environment and to repair damage from everyday life. Adaptation is thought to occur through the mechanosensitive response controlling the bone-forming and -resorbing cells. This report shows a way to extract quantitative information about the way remodeling is controlled using computer simulations. Bone resorption and deposition are described as two separate stochastic processes, during which a discrete bone packet is removed or deposited from the bone surface. The responses of the bone-forming and -resorbing cells to local mechanical stimuli are described by phenomenological remodeling rules. Our strategy was to test different remodeling rules and to evaluate the time evolution of the trabecular architecture in comparison to what is known from μ-CT measurements of real bone. In particular, we tested the reaction of virtual bone to standard therapeutic strategies for the prevention of bone deterioration, i.e., physical activity and medications to reduce bone resorption. Insensitivity of the bone volume fraction to reductions in bone resorption was observed in the simulations only for a remodeling rule including an activation barrier for the mechanical stimulus above which bone deposition is switched on. This is in disagreement with the commonly used rules having a so-called lazy zone

Towards disappearing user interfaces for ubiquitous computing: human enhancement from sixth sense to super senses

The enhancement of human senses electronically is possible when pervasive computers interact unnoticeably with humans in Ubiquitous Computing. The design of computer user interfaces towards “disappearing” forces the interaction with humans using a content rather than a menu driven approach, thus the emerging requirement for huge number of non-technical users interfacing intuitively with billions of computers in the Internet of Things is met. Learning to use particular applications in Ubiquitous Computing is either too slow or sometimes impossible so the design of user interfaces must be naturally enough to facilitate intuitive human behaviours. Although humans from different racial, cultural and ethnic backgrounds own the same physiological sensory system, the perception to the same stimuli outside the human bodies can be different. A novel taxonomy for Disappearing User Interfaces (DUIs) to stimulate human senses and to capture human responses is proposed. Furthermore, applications of DUIs are reviewed. DUIs with sensor and data fusion to simulate the Sixth Sense is explored. Enhancement of human senses through DUIs and Context Awareness is discussed as the groundwork enabling smarter wearable devices for interfacing with human emotional memories

Protein disorder-order interplay to guide the growth of hierarchical mineralized structures

A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder–order interplay using elastin-like recombinamers to program organic–inorganic interactions into hierarchically ordered mineralized structures. The materials comprise elongated apatite nanocrystals that are aligned and organized into microscopic prisms, which grow together into spherulite-like structures hundreds of micrometers in diameter that come together to fill macroscopic areas. The structures can be grown over large uneven surfaces and native tissues as acid-resistant membranes or coatings with tuneable hierarchy, stiffness, and hardness. Our study represents a potential strategy for complex materials design that may open opportunities for hard tissue repair and provide insights into the role of molecular disorder in human physiology and pathology

Optics and Quantum Electronics

Contains table of contents for Section 2 and reports on eighteen research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001)Charles Stark Draper Laboratory (Grant DL-H-285408)Charles Stark Draper Laboratory (Grant DL-H-2854018)National Science Foundation (Grant EET 87-03404)National Science Foundation (Grant ECS 84-06290)U.S. Air Force - Office of Scientific Research (Contract F49620-88-C-0089)AT&T Bell FoundationNational Science Foundation (Grant ECS 85-52701)National Institutes of Health (Grant 5-RO1-GM35459)Massachusetts General Hospital (Office of Naval Research Contract N00014-86-K-0117)Lawrence Livermore National Laboratory (Subcontract B048704

Are CT-Based Finite Element Model Predictions of Femoral Bone Strengthening Clinically Useful?

Purpose of Review: This study reviews the available literature to compare the accuracy of areal bone mineral density derived from dual X-ray absorptiometry (DXA-aBMD) and of subject-specific finite element models derived from quantitative computed tomography (QCT-SSFE) in predicting bone strength measured experimentally on cadaver bones, as well as their clinical accuracy both in terms of discrimination and prediction. Based on this information, some basic cost-effectiveness calculations are performed to explore the use of QCT-SSFE instead of DXA-aBMD in (a) clinical studies with femoral strength as endpoint, (b) predictor of the risk of hip fracture in low bone mass patients. Recent Findings: Recent improvements involving the use of smooth-boundary meshes, better anatomical referencing for proximal-only scans, multiple side-fall directions, and refined boundary conditions increase the predictive accuracy of QCT-SSFE. Summary: If these improvements are adopted, QCT-SSFE is always preferable over DXA-aBMD in clinical studies with femoral strength as the endpoint, while it is not yet cost-effective as a hip fracture risk predictor, although pathways that combine both QCT-SSFE and DXA-aBMD are promising

Optics and Quantum Electronics

Contains reports on eleven research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAALO03-86-K-O002)Charles Stark Draper Laboratory, Inc. (Grant DL-H-2854018)National Science Foundation (Grant DMR 84-18718)National Science Foundation (Grant EET 87-03404)National Science Foundation (ECS 85-52701)US Air Force - Office of Scientific Research (Contract AFOSR-85-0213)National Institutes of Health (Contract 5-RO1-GM35459)US Navy - Office of Naval Research (Contract N00014-86-K-0117

Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility