About the Book
Bone is a complex biological material that consists of both an inorganic and organic phase, which undergoes continuous dynamic biological processes within the body. This complex structure and the need to acquire accurate data have resulted in a wide variety of methods applied in the physical analysis of bone in vivo and in vitro. Each method has it
Table of Contents:
LIST OF CONTRIBUTORS, PREFACE, SECTION 1 INTRODUCTION, 1. ANATOMY, PHYSIOLOGY AND DISEASE, 1.1. Introduction, 1.2. Bone morphology and organization, 1.3. Bone tissue I: the role of bone cells, 1.3.1. The osteoclast, 1.3.2. The osteoblast, 1.3.3. The osteocytes, 1.4. Bone tissue II: the bony matrix, 1.5. Bone composition: mineralization of bone matrix, 1.6. Metabolic disorders of bone, 1.6.1. Introduction, 1.7. Osteoporosis, 1.7.1. Introduction, 1.7.2. Pathophysiology of osteoporosis, 1.7.3. Etiologic factors in osteoporosis, 1.7.4. Epidemiology, 1.8. Summary, References, 2. BIOLOGICAL SAFETY CONSIDERATIONS, 2.1. Introduction, 2.2. Duties and responsibilities, 2.3. Environmental protection, 2.4. Risk assessment, 2.5. Quantifying risk, 2.6. Acceptable risk, 2.7. Risk reduction, 2.8. Hierarchy of risk reduction, 2.9. Specific risks associated with the processing of bone, 2.9.1. Hazard identification, 2.10. Mechanical hazards, 2.10.1. Sawing bone, 2.10.2. Electrical hazards, 2.10.3. Chemical hazards, 2.11. Hazard identification, 2.11.1. Toxicity hazard, 2.11.2. Corrosive hazards, 2.11.3. Exposure limits, 2.11.4. Reactive hazards, 2.11.5. Flammability hazards, 2.12. Extinguishers, 2.13. Risk reduction and control: chemicals, 2.13.1. Fume cupboards, 2.13.2. Biological hazards, 2.14. Hazard categories of biological agents, 2.15. Hazard identification and hazard reduction at source, 2.15.1. For human bone, 2.15.2. For animal bone, 2.16. Prion diseases, 2.17. Biological control measures, 2.17.1. Allergens: control of exposure, 2.17.2. Microbiological safety cabinets, 2.17.3. Disinfectants, 2.17.4. Disinfection of cryostats, 2.17.5. Fumigation, 2.17.6. Disinfection of mechanical testing equipment and machine tools, 2.17.7. Autoclaves, 2.17.8. Disposal of biological waste, 2.17.9. Removal of equipment, 2.18. Use of personal protective equipment, 2.19. General managerial considerations, 2.19.1. Restricted access and permits to work, 2.19.2. Occupational health screening, 2.19.3. Prophylactic treatment, 2.20. Contents of a risk assessment, 2.20.1. Conveying the information to personnel, 2.20.2. Who should compile a risk assessment?, 2.21 Transport, packaging and labelling of biological samples, 2.22. Ionizing and non-ionizing radiation, 2.22.1. Ultraviolet light sources and lasers, 2.22.2. Genetic modification, References, 3. RADIATION SAFETY CONSIDERATIONS, 3.1. Introduction, 3.1.1. Units of radiation measurement, 3.1.2. Radiation detector, 3.2. Radiation dose to the patient, 3.2.1. Introduction, 3.2.2. Patient doses from dual X-ray absorptiometry, 3.2.3. Patient doses from fan beam DXA, 3.2.4. Doses from vertebral morphometry using DXA, 3.2.5. Paediatric doses from DXA, 3.2.6. Patient doses from QCT, 3.2.7. Patient dose from other techniques, 3.3. Staff dose from DXA, 3.4. Staff dose from other techniques, 3.5. Reduction of occupational dose, 3.6. Dose reduction techniques in DXA applications, 3.7. Problems with measuring patient and staff dose from absorptiometric techniques, 3.8. Conclusion, References, 4. INSTRUMENT EVALUATION, 4.1. Introduction, 4.2. Measurement errors, 4.2.1. Types of measurement error, 4.3. Equipment validation, 4.3.1. Precision, 4.3.2. Accuracy, 4.3.3. When are two measurements significantly different?, 4.4. Statistical methods in equipment validation, 4.4.1 Method-comparison studies, 4.4.2. Bland and Altman plot, 4.4.3. Regression analysis and correlations, 4.4.4. Clinical evaluation of a new device, 4.5. Quality assurance (QA), 4.5.1. Introduction, 4.5.2. Tools for QA, References, SECTION 2 INVASIVE TECHNIQUES, 5. MECHANICAL TESTING, 5.1. Introduction, 5.1.1. Bone, 5.1.2. Bone structure, 5.1.3. Why study the mechanical properties of bone?, 5.1.4. Basic concepts in bone mechanics and definition of terms, 5.2. Equipment and specimen consideration, 5.2.1. Equipment, 5.2.2. Specimen handling, 5.3. Methods of measuring the mechanical properties of bone tissue, 5.3.1. Uniaxial compressive test, 5.3.2. Uniaxial tensile test, 5.3.3. Bending test, 5.3.4. Torsion test, 5.3.5. Fatigue, 5.3.6. Indentation/hardness tests, 5.3.7. Ultrasound, 5.3.8. Conclusion, 5.4. Methods of measuring the mechanical properties of the trabeculae, 5.4.1. Microhardness, 5.4.2. Nano-indentation, 5.4.3. Buckling, 5.4.4. Ultrasound technique, 5.4.5. Other techniques, 5.4.6. Conclusions, 5.5. Factors Influencing the Mechanical Properties of Bone, 5.5.1. Specimen configuration, 5.5.2. Specimen preservation, 5.5.3. Bone hydration, 5.5.4. Sterilization, 5.5.5. Strain rate, 5.5.6. Age and disease, 5.5.7. Temperature, 5.5.8. Miscellaneous, 5.6. Mechanical properties of bone, 5.6.1. Introduction, 5.6.2. Mechanical properties of cancellous bone, 5.6.3. Mechanical properties of cortical bone, References, 6. HISTOMORPHOMETRY, 6.1. Introduction, Section A: Microarchitecture using computerized and, manual techniques, 6.2. Trabecular architecture—non-invasive, non-destructive, 6.3. Trabecular architecture—two-dimensional histology, 6.4. The trabecular analysis system (TAS), 6.5. Trabecular architecture—three-dimensional image, 6.5.1. Serial section techniques, 6.5.2. Thick slice technique, Section B: Microfracture and microcallus, Section C: Matrix remodelling, 6.6. Computer-assisted histomorphometry, 6.6.1. The OsteoMeasure system, 6.6.2. Tetracycline labelling and staining of the, calcification front, 6.7. Acknowledgments, References, 7. MICROSCOPY AND RELATED TECHNIQUES, 7.1. Introduction, Section A: Molecular labelling, 7.2. Radioisotope-labelling of bone—autoradiography, 7.3. Cryomicrotomy, bone bistology and Immunohistochemistry, 7.3.1. Immunohistochemistry, 7.3.2. Immunohistochemistry of the extracellular matrix, 7.3.3. Immunohistochemistry and colloidal gold labelling, 7.3.4. In situ hybridization, 7.4. Laser confocal microscopy, Section B: Mineral microanalysis and morphology, 7.5. Mineral density, 7.5.1. Ashing and volume displacement, 7.5.2. Density gradient fractionation of powdered bone, 7.6. Mineral Microanalysis, 7.6.1. Microradiography, 7.6.2. Backscattered electron image analysis, 7.6.3. Electron probe X-ray microanalysis (by specialist Dr Roger C Shore), 7.7. Mineral morphology, 7.7.1. Scanning electron microscopy, 7.7.2. High velocity impact (‘slam’) freezing, 7.7.3. Atomic and chemical force microscopy (by specialist Prof. Jennifer Kirkham), 7.8 Acknowledgments, References, SECTION 3 IONIZING RADIATION TECHNIQUES, 8. ABSORPTIOMETRIC MEASUREMENT, 8.1. Introduction, Section A: Fundamental principles of radiation physics, 8.2. Fundamentals of radiation physics, 8.2.1. γ-rays, 8.2.2. X-rays, 8.2.3. Inverse square law, 8.3. Interaction of X-rays and γ-rays with matter, 8.3.1. Introduction, 8.3.2. Interaction mechanism, 8.3.3. Attenuation in tissue, Section B: Instrumentation and principles, 8.4. Generation of X-ray, 8.4.1. Introduction, 8.4.2. X-ray spectrum, 8.4.3. Factors affecting the X-ray spectrum, 8.5. Physical principles of absorptiometry, 8.5.1. Single energy (γ-ray or X-ray) absorptiometry, 8.5.2. Dual energy absorptiometry, 8.5.3. Implementation of DXA, Section C: Clinical applications, 8.6. Sites measured, 8.6.1. Lumbar spine, 8.6.2. Lateral spine, 8.6.3. Proximal femur, 8.6.4. Peripheral sites, 8.6.5. Total body and body composition, 8.6.6. Vertebral morphometry, 8.7. Radiation dose to the patient, 8.8. Sources of in vivo measurement error, 8.8.1. Accuracy, 8.8.2. Precision, 8.8.3. Other error sources, 8.9. Quality assurance and quality control, 8.9.1. Quality assurance, 8.9.2. Cross calibration, 9. QUANTITATIVE COMPUTED TOMOGRAPHY, 9.1. Introduction, 9.2. Single-slice spinal bone mineral density measurement, 9.3. Physical significance of QCT measurements, 9.4. Measurement of BMD using volumetric CT images of the spine and hip, References, 10. PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY AND MICRO-COMPUTED TOMOGRAPHY, 10.1. Introduction, 10.2. Development of pQCT, 10.3. pQCT machine description, 10.4. Bone properties and variables measured by pQCT, 10.5. pQCT accuracy and precision for bone mineral and bone geometry assessments, 10.6. Clinical utility of pQCT, 10.7. Use of pQCT in pre-clinical testing, 10.8. Introduction to μCT, 10.9. What can be measured with μCT?, 10.10. Summary, References, 11. RADIOGRAMMETRY, 11.1. Overview, 11.2. Introduction, Section A: Fundamental principles of radiogrammetry, 11.3. Basic one-dimensional radiogrammetric measurements from two-dimensional planar images, 11.4. The cortical index, 11.5. Precision of basic one-dimensional radiogrammetry measurement, 11.6. Extending radiogrammetry from one-dimensional to two-dimensional measurement, 11.7. Conversion of two-dimensional radiogrammetric measurements to bone volume per area, 11.8. Conversion of calculated bone volume to bone mineral density (BMD), 11.9. Extending radiogrammetry to two-dimensional areas and three-dimensional volumes from two-dimensional cross-sectional slices, 11.10. Extending radiogrammetry from two-dimensional slice measurement to true three-dimensional, Section B: Limiting factors in radiogrammetry, 11.11. Image sharpness and image geometry, Section C: The clinical application of radiogrammetry, 11.12. Implementing a new radiogrammetry technique in a clinical setting, 11.13. Choosing an appropriate target condition, 11.14. Choosing the target bone, 11.15. Choosing the modality, 11.16. Establishing the image geometry, 11.17. Choosing the means of measurement, 11.18. The need for comparative reference, 11.19. Measurement validity, 11.20. Further research opportunities in radiogrammetry, References, 12. IN VIVO NEUTRON ACTIVATION ANALYSIS AND PHOTON SCATTERING, 12.1. Introduction, 12.2. In vivo neutron activation analysis (IVNAA), 12.2.1. Delayed gamma techniques, 12.2.2. Prompt gamma techniques, 12.2.3. Clinical applications and conclusion, 12.3. Photon scattering methodologies in measurement of bone density, 12.3.1 Theory, 12.3.2. Techniques, 12.3.3. Conclusions, References, SECTION 4 NON-IONIZING TECHNIQUES, 13. MAGNETIC RESONANCE IMAGING, 13.1. Introduction, 13.2. Quantitative magnetic resonance (QMR), 13.3. Imaging of trabecular bone structure, 13.3.1. In vitro studies, 13.3.2. Animal models, 13.3.4. In vivo human studies, 13.4. Conclusion, 13.5. Acknowledgment, References, 14. QUANTITATIVE ULTRASOUND, Section A: Fundamentals of ultrasound propagation, 14.1. Terminology, 14.1.1. Ultrasound, 14.1.2. Frequency, 14.2. Ultrasound propagation through materials, 14.2.1. Spring model propagation, 14.2.2. Modes of wave propagation, 14.2.3. Velocity of ultrasound waves, 14.2.4. Propagation velocity dependence, 14.2.5. Phase and group velocity, 14.3. Amplitude, intensity and attenuation, 14.3.1. Amplitude and intensity, 14.3.2. Attenuation, 14.3.3. Broadband ultrasound attenuation, 14.4. Interface behaviour, 14.4.1. Acoustic impedance, 14.4.2. Normal incidence at a tissue interface, 14.4.3. Non-normal incidence at a tissue interface, 14.4.4 Coupling, 14.5. Ultrasound wave formats, 14.5.1. Continuous, tone-burst and pulsed waves, 14.5.2. Bandwidth theorem, 14.5.3. Frequency spectrum and Q factor, Section B: Instrumentation, 14.6. The ultrasound transducer and beam profile, 14.6.1. Piezoelectric effect and transducer, 14.6.2. Transducer design, 14.6.3. Beam profile, 14.6.4. Focusing, 14.7. Instrumentation, 14.7.1 Pulse–echo technique, 14.7.2. Transmission technique, 14.7.3. Simple radio-frequency (RF) system, 14.7.4. Integrated pulse–echo system, 14.7.5. Rectilinear scanning, 14.7.6. Backscattering analysis, Section C: Theoretical modelling, 14.8. Biot theory, 14.9. Schoenberg’s theory, 14.10 Other models, Section D: In vitro experiments, 14.11. Bone samples, 14.11.1. Source, 14.11.2. Sample size and shape, 14.11.3. Sample preparation, 14.12. Measurement: methodology and analysis, 14.12.1. Coupling, 14.12.2. Transducers, 14.12.3. Transit time velocity measurements, 14.12.4. Alternative velocity measurements, 14.12.5. Critical angle reflectometry, 14.12.6. Attenuation, 14.12.7. Error sources, 14.13. In vitro experimental findings, 14.13.1. QUS and bone density, 14.13.2. QUS and mechanical properties, 14.13.3. QUS and bone structure, Section E: In vivo clinical assessment, 14.14. Commercial systems, 14.14.1. Anatomical sites, 14.14.2. Methodology: coupling, 14.14.3. Methodology: measurement variables, 14.14.4. Quality assurance, 14.14.5. Cross-calibration, 14.14.6. Artefacts and sources of errors, 14.15. In vivo application of ultrasound, 14.15.1. In vivo studies, 14.15.2. In vivo QUS measurement, 14.15.3. Age-related change, 14.15.4. Velocity diagnostic sensitivity, 14.15.5. BUA diagnostic sensitivity, 14.15.6. QUS and longitudinal monitoring, 14.15.7. Paediatric application, 14.15.8. Application to rheumatoid arthritis, References, 15 FINITE ELEMENT MODELLING, 15.1. Introduction, Section A: Finite element analysis of bone: general considerations, 15.2. Fundamentals of FE analysis, 15.3. FE analysis applied to bone, 15.3.1 Structural and solid mechanics FE analysis, 15.3.2. Poroelastic FE analysis, 15.3.3. Other types of FE analysis, 15.4. Generation of FE models, 15.5. Equipment and software, Section B: Bone mechanical characterization and fe modelling at different levels of structural organization, 15.6. The whole bone (apparent) level, 15.6.1. Structural characterization, 15.6.2. Mechanical characterization, 15.6.3. FE modelling, 15.7. The trabecular bone level, 15.7.1. Structural characterization, 15.7.2. Mechanical characterization, 15.7.3. FE modelling, 15.8. Bone tissue and ultrastructural level, 15.8.1. Structural characterization, 15.8.2. Mechanical characterization, 15.8.3. FE modelling, Section C: FE analysis of bone and bones at the organ level:, contemporary applications and results, 15.9. Analysis of bone mechanical properties and loading, 15.9.1. Bone failure load, 15.9.2. Bone fracture healing and tissue differentiation analysis, 15.9.3. Consequences of orthopaedic implants and interventions, 15.10. Clinical assessment of bone mechanical properties, 15.11. Simulation of mechanically induced biological processes, 15.11.1. Bone remodelling, 15.11.2. Tissue differentiation and fracture healing, Section D: FE analysis at the bone trabecular level: recent applications and results, 15.12. Analysis of bone mechanical properties and loading, 15.12.1. Elastic properties, 15.12.2. Strength and yield properties, 15.12.3. Assessment of physiological bone tissue loading, 15.13. Clinical assessment of bone mechanical properties, 15.14. Simulation of mechanically induced biological processes, 15.14.1. Bone remodelling, 15.15. Summarizing conclusion, References, 16 VIBRATION ANALYSIS, Section A: Introduction, 16.1. Condition monitoring of machinery, 16.2. Modal analysis, 16.3. Non-destructive testing, 16.3.1. Transverse (flexural) vibration methodology, 16.4. Vibrational measurements applied to bone, Section B: Material properties of whole long bones, 16.5. Frequency response measurements, 16.5.1. Early studies, 16.5.2. Impulse frequency response (IFR) technique, 16.5.3. Bone resonance analysis (BRA) technique, 16.5.4. Comparison of IFR and BRA techniques, 16.5.5. Mechanical response tissue analysis (MRTA), 16.5.6. Effect of soft tissue on frequency, 16.6. Longitudinal wave propagation, 16.6.1. One-point method, 16.6.2. Two-point method, 16.7. Association of resonant frequency with torsional and bending stiffness, 16.8. Use of vibration to monitor treatment effect, 16.9. Vibration modelling studies, 16.9.1. Ulnar model, 16.9.2. Tibia model, 16.9.3. Femur model, 16.10. Summary, Section C: The use of vibration in the monitoring of fracture healing, 16.11. Introduction, 16.12. Low frequency wave propagation, 16.12.1. Propagation and measurement of low frequency waves (‘stress waves’), 16.12.2. In vitro results, 16.12.3. In vivo results, 16.13. Resonant frequency measurement, 16.13.1. Swept sinusoidal vibration, 16.13.2. Impulse-response method, 16.14. Modelling of the effect of healing, 16.15. Other measurements, 16.16. Summary, Section D: The use of vibration in the diagnosis of prosthesis loosening, 16.17. Summary, References, 17 HUMAN STUDIES, 17.1. Introduction, Section A: Presentation of BMD, 17.2. Units of measure, 17.3. Reference population, 17.4. T-scores, 17.5. Z-scores, Section B: Interpretation of BMD Results, 17.6. WHO criteria, 17.7. Limitations of WHO criteria, 17.8. NOF recommendations, 17.9. Fracture risk assessment, Section C: Utility of BMD, 17.10. Who should be tested?, 17.11. How to apply BMD, 17.12. Diagnostic algorithms, Section D: Which Site to Measure, 17.13. Available sites, 17.14. Limitations, 17.15. Combining sites to increase diagnostic power, Section E: Treatment Considerations, Section F: Measurement errors, 17.16. Conclusions, References, 18 ANIMAL STUDIES, 18.1. Introduction, 18.2. Animals models, 18.2.1. Introduction, 18.2.2. Modelling osteoporosis in animals, 18.2.3. Rat as a model for osteoporosis, 18.2.4. Sheep as a model of osteoporosis, 18.3. Bone status measurements, 18.3.1. Introduction, 18.3.2. Bone density, 18.3.3. Bone structure, 18.3.4. Bone biomechanical properties, 18.4. Techniques for measuring bone density, 18.4.1. Dual X-ray absorptiometry (DXA), 18.4.2. Peripheral dual X-ray absorptiometry, 18.4.3. Peripheral quantitative computed tomography (pQCT), 18.5. Techniques for measuring bone structure, 18.5.1. Introduction, 18.5.2. Radiography, microradiography and radiogrammetry, 18.5.3. Peripheral quantitative computed tomography (pQCT), 18.5.4. Micro-computed tomography (μCT), 18.5.5. Synchrotron radiation μCT, 18.5.6. μCT three-dimensional assessment, 18.5.7. Magnetic resonance imaging (MRI) microscopy, 18.5.8. Histomorphometry, 18.6. Bone strength measurement, 18.7. Summary and perspectives, References, INDEX
About the Author :
Dr Christian M Langton Centre for Metabolic Bone Disease, Hull Royal Infirmary, Anlaby Road, Hull HU3 2RW, UK Dr Christopher F Njeh The John Hopkins University, School of Medicine, Division of Radiation Oncology, The Harry and Jeanette Weinberg Building, 401 North Broadway, Suite 1440, Baltimore, MD 21231-1240, USA
