Basic and Applied Bone Biology

Description

Cover......Page 1 BASIC AND APPLIED BONE BIOLOGY......Page 2 Copyright......Page 3 Dedication......Page 4 List of Contributors......Page 5 Biographies......Page 7 Preface (First Edition)......Page 8 Preface (Second Edition)......Page 10 Part I: Basic Bone Biology and Physiology ......Page 11 The Functions of Bone......Page 12 Bone Is Organized as a Multiscale Material......Page 13 Collagen......Page 14 Enzymatically Mediated Collagen Cross-Linking......Page 16 Collagen Orientation......Page 17 Bone Mineral......Page 18 Proteoglycans and Glycosaminoglycans......Page 19 SIBLING Proteins......Page 21 Woven Bone......Page 22 Plexiform Bone......Page 23 Primary Osteons......Page 24 Secondary Bone......Page 25 Cancellous Bone1......Page 26 Skeletal Envelopes......Page 28 Blood Supply......Page 29 Bone Fluid Compartments......Page 31 Tissue Material (Intrinsic) Properties......Page 32 Microdamage Accumulation......Page 34 Suggested Readings......Page 35 2 - Bone Marrow and the Stem Cell Niche......Page 36 Niches in Development......Page 37 Imaging of Niches......Page 38 Mesenchymal Stromal/Stem Cell Populations......Page 39 Endothelial Cells......Page 40 Osteoclasts......Page 41 Niches and Malignancies......Page 42 The Future......Page 43 Suggested Readings......Page 44 Osteoclast Morphology and Function......Page 45 Osteoclast Differentiation and Fusion......Page 49 Regulation of Osteoclast Generation and Survival......Page 52 Osteoblast Morphology and Function......Page 53 Osteoblast Formation and Differentiation......Page 54 Osteoblast Apoptosis......Page 55 Bone Lining Cells......Page 56 Osteocytes......Page 57 Osteocyte Morphology and Functions......Page 58 Preservation of Osteocyte Viability by Mechanical Stimuli......Page 59 Aging and Osteocyte Apoptosis......Page 60 Regulation of Bone Mineralization by Osteocytes......Page 61 Suggested Readings......Page 63 Soluble Ligands......Page 64 Signal Transduction Cascades......Page 65 The RANKL–RANK–OPG System......Page 66 Wnts......Page 68 Noncanonical Wnt Signaling......Page 70 Kremen......Page 71 Insulin-Like Growth Factor......Page 72 Fibroblast Growth Factors......Page 75 Interleukins......Page 77 Tumor Necrosis Factor......Page 79 Bone Morphogenetic Proteins......Page 80 Transforming Growth Factor Beta......Page 81 Regulation of Transforming Growth Factor Beta Bioavailability......Page 82 Prostaglandins......Page 83 Notch......Page 84 Ephrin–Ephrin Receptor......Page 85 Connexins......Page 86 Local Angiogenic Factors That Regulate Bone Cell Activity......Page 87 Cell Surface Attachment Molecules......Page 88 Suggested Readings......Page 90 Endochondral Ossification......Page 92 Bone Modeling......Page 96 Radial Growth......Page 97 Bone Remodeling......Page 98 Events That Signal Remodeling......Page 99 Resorption......Page 100 Reversal......Page 101 Bone Remodeling Cycle Duration......Page 102 Bone Remodeling Balance......Page 103 Mineralization......Page 104 Laboratory Assessment of Modeling and Remodeling......Page 105 Suggested Readings......Page 107 Part II: Assessment of Bone Structure and Function ......Page 108 Conventional Radiography......Page 109 Dual-Energy X-ray Absorptiometry......Page 111 Clinical Diagnostic Computed Tomography......Page 114 Dual Energy or Spectral Imaging Scanning......Page 118 Microcomputed Tomography......Page 119 Quantitative Computed Tomography (Densitometry)......Page 121 Modeling Analysis......Page 122 Magnetic Resonance Imaging......Page 124 Radionuclide Imaging......Page 125 Positron Emission Tomography and Positron Emission Tomography–Computed Tomography......Page 127 Summary......Page 128 Ultrasound......Page 129 Bone Is a Hierarchical Structure......Page 130 Stress and Strain in Axial Loading......Page 131 Axial Loading in Tension and Compression......Page 134 Torsion......Page 135 Bending......Page 136 Bone Mass: Cancellous Bone......Page 138 Cortical Bone Size (Mass) and Architecture......Page 139 Bone Tissue Material Properties......Page 140 The Bone Extracellular Matrix: Type I Collagen......Page 141 The Bone Extracellular Matrix: Inorganic Hydroxyapatite......Page 142 Methods of Testing the Mechanical Properties of Bone Tissue......Page 143 Other Measures of Bone “Strength”......Page 144 Suggested Readings......Page 145 Specimen Collection......Page 146 In Vivo Labeling......Page 147 Specimen Processing......Page 148 Histomorphometric Analysis......Page 150 Bone Architecture and Geometry......Page 151 Tissue Types......Page 152 Cell Number and Activity......Page 153 Dynamic Histomorphometry......Page 154 Osteocytes......Page 156 Assumptions and Technical Aspects......Page 157 Osteoporosis......Page 158 Secondary Hyperparathyroidism......Page 159 Antiresorptive Therapy......Page 160 Anabolic Therapy......Page 162 Suggested Readings......Page 163 Linkage Analysis......Page 164 Genome-Wide Association Studies......Page 165 Whole Exome and Whole Genome Analysis......Page 167 Omics Analysis of Bone Phenotypes......Page 168 Animals Derived From Homologous Recombination in ES Cells......Page 169 Superovulation......Page 170 DNA Preparation for Microinjection......Page 171 Transfer of Injected Embryos to Recipient Females......Page 172 Microinjection of Genetically Modified Embryonic Stem Cells......Page 175 Generation of ES cell Lines......Page 176 Collection of Blastocysts......Page 177 Transfer of Injected Blastocysts to Recipient Females......Page 178 Identification of Chimeric Animals......Page 179 Designer DNA Nucleases: The CRISPR Revolution......Page 180 Transgenic Animals and Bone Biology......Page 184 Bone Cell–Specific Promoters......Page 185 Conditional Models Using Cre-LoxP Technology......Page 186 Bridging Human Disorders and Mouse Models of Bone Diseases......Page 187 Secondary Challenges and Genetic Background Impacts on Skeletal Phenotypes......Page 188 Suggested Readings......Page 189 Part III: Skeletal Adaptation ......Page 191 Development and Maturation......Page 192 Infancy and Childhood Skeletal Growth......Page 193 Puberty and Adolescence......Page 195 Race and Ethnic Differences......Page 196 Endocrine Regulators......Page 197 Genetic Regulation......Page 198 Timing of Growth Rates......Page 199 Fracture Risk in Children......Page 200 Pregnancy......Page 201 Skeletal Expansion and Age......Page 202 Skeletal Mass and Age......Page 203 Other reading......Page 205 Wolff’s Law—A Historical Perspective......Page 206 Strain Magnitude......Page 207 Strain Frequency......Page 208 Intrinsic Loading Models......Page 209 Invasive (Surgical) Models......Page 210 Noninvasive Models......Page 211 Bone Responds Only Above (or Below) a Threshold of Strain or Strain Rate......Page 212 Rate-Related Phenomena are Critical to Response......Page 213 The Mechanostat......Page 214 Modeling and Remodeling are Antagonistic Processes......Page 215 Bone Formation on the Different Envelopes is Controlled by Local Conditions......Page 216 A Test of Wolff’s Law......Page 217 Mechanotransduction on a Smaller Scale: Cell Types and Their Environment......Page 219 Fluid Flow in Bone Tissue Has Manifold Cellular Effects......Page 220 Cellular Deformation and Stimulation......Page 221 Ion Channels......Page 223 Cell Adhesion and the Cytoskeleton......Page 224 G Protein Signaling......Page 225 Coordinating the Biochemical Response to Mechanical Stimulation......Page 226 Childhood and Adolescence......Page 229 Skeletal Responses to Physical Activity and Exercise in Adulthood......Page 230 Principle of Specificity......Page 231 Principle of Progressive Overload......Page 233 Principle of Diminished Returns......Page 235 Suggested Readings......Page 236 Types of Bone Fracture......Page 237 Inflammatory Response......Page 238 Hard Callus Formation (Endochondral Ossification)......Page 239 Bone Remodeling......Page 241 Methods of Evaluation......Page 242 Cellular Events of Fracture Repair......Page 243 Molecular Regulation of Chondrogenesis and Osteogenesis During Fracture Repair......Page 244 Prostaglandins......Page 246 Platelet-Derived Growth Factor......Page 247 Vascular Endothelial Growth Factor......Page 248 Skeletal Muscle Interactions......Page 249 Aging......Page 250 Glucocorticoids......Page 251 Parathyroid Hormone......Page 252 Denosumab......Page 253 Summary......Page 254 Suggested Readings......Page 255 Part IV: Hormonal and Metabolic Effects on Bone ......Page 256 Distribution of Calcium and Phosphorus in the Body......Page 257 Mineral Accrual and Loss Over the Life Span......Page 259 Regulation of Whole Body Calcium Metabolism......Page 260 Intestinal Calcium Absorption......Page 261 Renal Calcium Reabsorption......Page 264 25-Hydroxyvitamin D Metabolism......Page 266 1,25-Dihydroxyvitamin D Regulation and Metabolism......Page 267 Vitamin D Actions......Page 268 Parathyroid Hormone and Parathyroid Hormone-Related Peptide......Page 269 Control of PTH Production and Release......Page 270 Estrogen......Page 272 Hormones of Pregnancy and Lactation......Page 273 Regulation of Whole Body Phosphate Metabolism......Page 274 Intestinal Phosphate Absorption......Page 276 Fibroblast Growth Factor 23 is an Important Hormone in Phosphate Reabsorption and Vitamin D Regulation......Page 279 Influence of Iron on FGF23 Metabolism......Page 280 Summary......Page 281 Suggested Readings......Page 282 Macro- and Micronutrient Roles in Bone Health......Page 283 When and How Nutrients Influence Bone Mass......Page 288 Perturbing Calcium Metabolism......Page 289 Diet Versus Fortified Foods Versus Supplements......Page 291 Acid–Base Balance, Fruit and Vegetable Intakes, and Bone Health......Page 292 Dietary Bioactives and Their Mechanisms......Page 293 Obesity, Osteoporosis, and Fracture Risk......Page 294 Effects of Weight Loss on Bone......Page 295 Challenges for Studying Effects of Nutrient Interventions on Bone Outcomes......Page 296 Suggested Readings......Page 298 PTH Receptors and Downstream Signaling......Page 299 Downregulation of Sost/Sclerostin by PTH......Page 300 Sex Steroids......Page 301 Sex Steroid Receptor Signaling......Page 302 Sex Steroids During Growth......Page 303 Changes in Bone Cells Induced by Estrogen Deficiency......Page 304 Epidemiology and Progression of Glucocorticoid-Induced Bone Disease......Page 305 Glucocorticoid Receptors and Downstream Signaling......Page 306 Thyroid Hormone......Page 307 Growth Hormone......Page 308 Insulin......Page 310 Leptin......Page 311 Other Hormones......Page 313 Part V: The Interaction of Bone With Other Organ Systems ......Page 314 Embryogenesis and Development......Page 315 Muscle Structure......Page 317 The Mechanical Interaction of Muscle and Bone......Page 319 Endocrine Cross Talk Between Muscle and Bone......Page 320 Myostatin......Page 322 Musclin......Page 323 RANKL......Page 324 Fibroblast Growth Factor 23......Page 325 Osteogenesis Imperfecta......Page 326 Cachexia......Page 327 Sarcopenia......Page 328 Suggested Readings......Page 330 Innate Immunity......Page 331 Adaptive Immunity......Page 332 B Cells and Bone Remodeling......Page 335 T Cells and Bone Remodeling......Page 336 Infections and Bone Cells......Page 337 Endocrine Activation of Immune-Mediated Bone Loss......Page 339 Role of Immune Activation in Estrogen Deficiency......Page 340 Role of T Cells in Parathyroid Hormone Responses in Bone......Page 341 Rheumatoid Arthritis......Page 342 Suggested Readings......Page 344 Introduction to the Nervous System......Page 346 Innervation of Bone......Page 347 Neural Connections Between Bone and Brain......Page 350 The Sympathetic Nervous System......Page 353 Leptin......Page 355 Serotonin......Page 357 Neuropeptide Y......Page 358 Dopamine......Page 359 Pituitary Adenylate Cyclase–Activating Polypeptide and Vasoactive Intestinal Peptide......Page 360 Calcitonin Gene–Related Peptide......Page 361 Substance P......Page 362 Bone Feedback to the Brain......Page 363 Suggested Readings......Page 364 Introduction to the Microbiome......Page 365 Preclinical Manipulations of the Microbiome......Page 367 The Effects of the Microbiome on Bone Mass, Remodeling, and Strength......Page 368 Mechanisms Linking the Microbiome to Bone......Page 369 Suggested Readings......Page 370 20 - Bone and Kidney......Page 371 Renal Osteodystrophy......Page 373 Bone Imaging......Page 374 Pathogenesis of Abnormal Bone in Patients With CKD......Page 376 Abnormal Hormones......Page 378 CKD-MBD—Biochemical Abnormalities......Page 379 CKD-MBD—Vascular Calcification......Page 380 Summary......Page 381 Suggested Readings......Page 382 Part VI: Skeletal Disease and Treatment ......Page 383 Definition......Page 384 Risk Factors......Page 386 Pathogenesis......Page 388 Calcium and Vitamin D......Page 389 Estrogen......Page 391 Selective Estrogen Receptor Modulators......Page 392 Bisphosphonates......Page 393 Denosumab......Page 398 Anabolic Therapies......Page 399 Teriparatide......Page 400 Antisclerostin Antibody......Page 401 Treatment Guidelines and Decisions......Page 402 Sequential Treatments......Page 403 Concurrent Antiremodeling Agent and Anabolic......Page 404 Suggested Readings......Page 405 22 - Bone and Cancer......Page 406 Abnormalities of Bone Remodeling Induced by Cancer in Bone......Page 407 Mechanisms Responsible for Bone Metastasis......Page 408 Changes in the Phenotype of Cancer Cells Induced by the Bone Microenvironment......Page 409 Generation of the Premetastatic Niche in Bone......Page 410 Contributions of Bone Cells to Tumor Cell Dormancy, Reactivation, Chemoresistance, and Tumor Progression in Bone......Page 411 Role of Osteoclasts in the Development and Progression of Bone Metastasis......Page 412 Role of Osteoblasts in the Development and Growth of Bone Metastasis......Page 413 Bone Turnover Markers and Other Biomarkers of Cancer in Bone......Page 416 Bone-Targeted Therapies for Bone Metastasis......Page 417 Suggested Readings......Page 418 Introduction......Page 419 Fracture Risk in Type 1 Diabetes......Page 421 Skeletal Changes in Diabetes......Page 424 Bone Geometry and Architecture in Type 1 Diabetes......Page 425 Mineral Homeostasis and Bone Turnover in Diabetes......Page 427 Osteocalcin......Page 428 Bone Tissue Material Properties......Page 429 Insulin......Page 430 GLP-1 Receptor Agonists......Page 431 Sodium-Glucose Cotransporter 2 Inhibitors......Page 432 Amylin Analogs......Page 433 Conclusions......Page 434 Suggested Readings......Page 435 A......Page 436 B......Page 437 C......Page 438 E......Page 440 F......Page 441 H......Page 442 I......Page 443 M......Page 444 N......Page 445 O......Page 446 P......Page 447 Q......Page 448 S......Page 449 T......Page 451 W......Page 452 Z......Page 453 Back Cover......Page 454