Non-invasive Predictors of Human Cortical Bone Mechanical Properties: T2-Discriminated 1H NMR Compared with High Resolution X-ray

Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, 1H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that 1H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These 1H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk

Ethical and Scientific Considerations Regarding Animal Testing and Research

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of animal use, principles which have since been referred to as the ‘‘3 Rs’’. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the ‘‘3 Rs’’ capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals, the individual interests of animals, or an updated understanding of potential harms associated with animal research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress 50 Years Later, which aims to spur ethical and scientific advancement

Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice - what their phenotypes reveal about mechanisms of estrogen action

Natural, synthetic and environmental estrogens have numerous effects on the development and physiology of mammals. Estrogen is primarily known for its role in the development and functioning of the female reproductive system. However, roles for estrogen in male fertility, bone, the circulatory system and immune system have been established by clinical observations regarding sex differences in pathologies, as well as observations following menopause or castration. The primary mechanism of estrogen action is via binding and modulation of activity of the estrogen receptors (ERs), which are ligand-dependent nuclear transcription factors. ERs are found in highest levels in female tissues critical to reproduction, including the ovaries, uterus, cervix, mammary glands and pituitary gland. Since other affected tissues have extremely low levels of ER, indirect effects of estrogen, for example induction of pituitary hormones that affect the bone, have been proposed. The development of transgenic mouse models that lack either estrogen or ER have proven to be valuable tools in defining the mechanisms by which estrogen exerts its effects in various systems. The aim of this article is to review the mouse models with disrupted estrogen signaling and describe the associated phenotypes

:4; Personal non-commercial use only

ABSTRACT. Objective. To develop novel quantitative and semiquantitative bone erosion measures at metacarpophalangeal (MCP) and wrist joints in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT), and to correlate these measurements with disease duration and bone marrow edema (BME) patterns derived from magnetic resonance imaging (MRI). Methods. Sixteen patients with RA and 7 healthy subjects underwent hand and wrist HR-pQCT and 3-Tesla MRI. Bone erosions of the MCP2, MCP3, and distal radius were evaluated by measuring maximal erosion dimension on axial slices, which is a simple and fast measurement, and then were graded (grades 0-3) based on the maximal dimension. Correlation coefficients were calculated between (1) sum maximal dimensions, highest grades, and sum grades of bone erosions; (2) erosion measures and the clinical evaluation; (3) erosion measures and BME volume in distal radius. Results. The inter-and intrareader agreements of maximal erosion dimensions were excellent (intraclass correlation coefficients 0.89, 0.99, and root mean square error 9.4%, 4.7%, respectively). Highest grades and sum grades were significantly correlated to sum maximal dimensions of all erosions. Number of erosions, sum maximal erosion dimensions, highest grades, and sum grades correlated significantly with disease duration. Number of erosions, sum maximal dimensions, and erosion grading of the distal radius correlated significantly with BME volume. Conclusion. HR-pQCT provides a sensitive method with high reader agreement in assessment of structural bone damage in RA. The good correlation of erosion measures with disease duration as well as BME volume suggests that they could become feasible measures of erosions in RA

Personal non-commercial use only

ABSTRACT. Objective. To develop novel quantitative and semiquantitative bone erosion measures at metacarpophalangeal (MCP) and wrist joints in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT), and to correlate these measurements with disease duration and bone marrow edema (BME) patterns derived from magnetic resonance imaging (MRI). Methods. Sixteen patients with RA and 7 healthy subjects underwent hand and wrist HR-pQCT and 3-Tesla MRI. Bone erosions of the MCP2, MCP3, and distal radius were evaluated by measuring maximal erosion dimension on axial slices, which is a simple and fast measurement, and then were graded (grades 0-3) based on the maximal dimension. Correlation coefficients were calculated between (1) sum maximal dimensions, highest grades, and sum grades of bone erosions; (2) erosion measures and the clinical evaluation; (3) erosion measures and BME volume in distal radius. Results. The inter-and intrareader agreements of maximal erosion dimensions were excellent (intraclass correlation coefficients 0.89, 0.99, and root mean square error 9.4%, 4.7%, respectively). Highest grades and sum grades were significantly correlated to sum maximal dimensions of all erosions. Number of erosions, sum maximal erosion dimensions, highest grades, and sum grades correlated significantly with disease duration. Number of erosions, sum maximal dimensions, and erosion grading of the distal radius correlated significantly with BME volume. Conclusion. HR-pQCT provides a sensitive method with high reader agreement in assessment of structural bone damage in RA. The good correlation of erosion measures with disease duration as well as BME volume suggests that they could become feasible measures of erosions in RA. (J Rheumatol First Releas