Contributors |
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xiii | |
Preface |
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xix | |
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Part I Components of the Organic Extracellular Matrix of Bone and Cartilage |
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Structure, Biosynthesis and Gene Regulation of Collagens in Cartilage and Bone |
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3 | (2) |
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5 | (2) |
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7 | (2) |
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9 | (5) |
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14 | (3) |
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Collagen Genes and Transcriptional Regulation |
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17 | (4) |
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Factors Regulating Collagen Biosynthesis |
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21 | (4) |
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25 | (16) |
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26 | (15) |
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Fibrillogenesis and Maturation of Collagens |
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41 | (1) |
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42 | (2) |
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44 | (6) |
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50 | (5) |
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50 | (5) |
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Vitamin K Dependent Proteins of Bone and Cartilage |
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55 | (1) |
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55 | (1) |
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56 | (3) |
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59 | (4) |
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63 | (1) |
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64 | (7) |
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65 | (6) |
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Noncollagenous Proteins; Glycoproteins and Related Proteins |
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71 | (1) |
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Cartilage Extracellular Matrix |
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72 | (5) |
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Bone, Extracellular Matrix |
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77 | (2) |
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79 | (6) |
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80 | (5) |
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Proteoglycans and Glycosaminoglycans |
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85 | (1) |
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86 | (1) |
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Proteoglycans in Cartilage |
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87 | (1) |
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88 | (5) |
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Leucine-rich Proteoglycans in Cartilage and Bone |
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93 | (3) |
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96 | (3) |
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96 | (3) |
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99 | (1) |
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Insulin-like Growth Factors |
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99 | (1) |
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The Transforming Growth Factor-Beta/Bone Morphogenetic Protein Superfamily |
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100 | (3) |
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Fibroblast Growth Factors |
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103 | (1) |
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104 | (1) |
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Additional Growth Factors |
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105 | (1) |
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106 | (9) |
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107 | (8) |
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Prostaglandins and Proinflammatory Cytokines |
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115 | (1) |
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115 | (2) |
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The Role that Cytokines have in Osteoclast Formation and Function |
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117 | (1) |
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The Role that Proinflammatory Cytokines have in Bone and Cartilage Metabolism |
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118 | (11) |
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121 | (8) |
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Integrins and Other Adhesion Molecules |
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129 | (1) |
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129 | (1) |
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Molecular Structure of Adhesion Molecules |
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130 | (4) |
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Adhesion Molecules in Cells of the Osteoblast Lineage |
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134 | (5) |
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Adhesion Molecules in Osteoclasts |
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139 | (3) |
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Adhesion Molecules in Chondrocytes |
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142 | (2) |
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144 | (9) |
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144 | (9) |
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153 | (1) |
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Structure and Regulation of the TNAP Gene |
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153 | (2) |
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155 | (2) |
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157 | (3) |
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160 | (5) |
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161 | (4) |
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165 | (1) |
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Tartrate-Resistant Acid Phosphatase (TRACP) |
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166 | (7) |
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Prostatic Acid Phosphatase (PAP) |
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173 | (8) |
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176 | (5) |
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181 | (1) |
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181 | (1) |
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182 | (2) |
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184 | (2) |
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186 | (15) |
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192 | (9) |
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Part II Structure and Metabolism of the Extracellular Matrix of Bone and Cartilage |
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Mineralization, Structure and Function of Bone |
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201 | (1) |
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The Structure and Function of Bone |
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201 | (3) |
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204 | (5) |
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Bone Modeling and Remodeling |
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209 | (4) |
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209 | (4) |
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Bone Structure and Strength |
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213 | (1) |
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Gravity and the Need for Stiffness, Flexibility, Lightness and Speed |
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213 | (1) |
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The Material Composition and Structural Design of Bone |
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214 | (2) |
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Bone Modeling and Remodeling -- The Mechanism of Bone's Construction during Growth and Decay with Advancing Age |
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216 | (1) |
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217 | (2) |
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219 | (2) |
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219 | (2) |
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221 | (1) |
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221 | (1) |
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Developmental Signals for Cartilage and Bone Tissue Formation |
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222 | (5) |
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227 | (9) |
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The Osteoclast: A Functionally Unique Cell for Physiologically Regulated Resorption of Bone Mineral |
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236 | (6) |
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242 | (17) |
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242 | (17) |
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259 | (1) |
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259 | (1) |
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The Control of Osteoclasts |
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260 | (1) |
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Signaling in the Control of Osteoclast Activity |
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261 | (1) |
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Signals from the Osteoblast Lineage that Control Osteoclast Formation |
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261 | (1) |
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Hormone and Cytokine Influences on the Contact-dependent Regulation of Osteoclasts |
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261 | (1) |
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Discovery of the Physiological Signaling Mechanisms in Osteoclast Control |
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262 | (1) |
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263 | (1) |
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Coupling of Bone Formation to Resorption -- Release of Growth Factors from bone Matrix |
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264 | (2) |
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Coupling of Bone Formation to Resorption -- Autocrine/Paracrine Regulation by Differentiating Osteoblasts |
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266 | (1) |
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Coupling of Bone Formation to Resorption -- Are Osteoclasts a Source of Coupling Activity? |
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266 | (7) |
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267 | (6) |
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Parathyroid Hormone: Structure, Function and Dynamic Actions |
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273 | (1) |
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Structure of the PTH Gene |
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273 | (1) |
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274 | (1) |
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Control of Gene Expression |
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275 | (3) |
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Biosynthesis of Parathyroid Hormone |
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278 | (1) |
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Metabolism of Parathyroid Hormone |
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278 | (1) |
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Receptor Interactions of Parathyroid Hormone and Parathyroid Hormone-Related Protein |
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279 | (1) |
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Structure of the PTH/PTHrP (PTH1R) Receptor |
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279 | (2) |
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Activation of the Cyclic Adenosine Monophosphate Second-Messenger System by Parathyroid Hormone |
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281 | (1) |
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Identification of a Second PTH Receptor |
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282 | (1) |
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Physiological Actions of PTH |
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282 | (2) |
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Cell-to-Cell Communication: Osteoblasts and Osteoclasts |
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284 | (1) |
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Preferential Actions of PTH at Selected Skeletal Sites |
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285 | (8) |
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287 | (6) |
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Interaction of Parathyroid Hormone-related Peptide with the Skeleton |
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293 | (1) |
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293 | (1) |
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Molecular Biology and Mechanism of Action |
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294 | (4) |
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The Skeletal Actions of PTHrP |
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298 | (3) |
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301 | (6) |
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302 | (5) |
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The Vitamin D Hormone and its Nuclear Receptor: Mechanisms Involved in Bone Biology |
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307 | (1) |
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308 | (1) |
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Nuclear Vitamin D Receptor |
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309 | (3) |
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312 | (2) |
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Pathology and Therapy Related to Vitamin D Availability, Metabolism, and Function |
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314 | (5) |
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319 | (8) |
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319 | (8) |
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Sex Steroid Effects on Bone Metabolism |
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327 | (1) |
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327 | (1) |
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Molecular Structures, Synthesis, Mechanism of Action of Major Sex Steroids, and Transcriptional Coregulator Function |
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328 | (3) |
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Effects of Sex Steroids on Bone Cells and Bone Turnover |
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331 | (4) |
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Effects of Estrogens and Androgens on Bone Metabolism in Men Versus Women |
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335 | (1) |
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Effects of Sex Steroids on Extraskeletal Calcium Homeostasis |
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336 | (1) |
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337 | (8) |
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338 | (7) |
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Physiology of Calcium and Phosphate Homeostases |
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345 | (1) |
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345 | (1) |
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Body Distribution of Calcium |
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346 | (1) |
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Determinants of Extracellular Calcium Concentration |
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346 | (3) |
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Relative Importance of the Various Calcium Fluxes in Controlling Extracellular Calcium Homeostasis |
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349 | (1) |
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Homeostatic Responses to Hypocalcemia |
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349 | (3) |
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352 | (1) |
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Body Distribution of Phosphorus |
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353 | (1) |
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Determinants of Extracellular Phosphate Concentration |
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353 | (3) |
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Homeostatic Responses to Changes in Phosphate Supply or Demand |
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356 | (1) |
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357 | (4) |
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357 | (4) |
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The Central Control of Bone Remodeling |
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361 | (1) |
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362 | (3) |
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Sympathetic Nervous System |
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365 | (4) |
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Neuropeptide Y and the Y Receptors |
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369 | (2) |
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Interaction between Leptin and Y2-Regulated Bone Antiosteogenic Pathways |
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371 | (2) |
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373 | (4) |
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373 | (4) |
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New Concepts in Bone Remodeling |
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377 | (1) |
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An Overview of the Remodeling Cycle |
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377 | (3) |
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Functions of Bone Remodeling |
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380 | (1) |
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The Role of Apoptosis in Regulating Bone Balance |
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381 | (2) |
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Possible Mechanisms whereby a Reduction in Activation Frequency may Protect against Fracture |
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383 | (8) |
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386 | (5) |
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Products of Bone Collagen Metabolism |
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391 | (1) |
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Products of Bone Collagen Synthesis, the Procollagen Propeptides |
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392 | (5) |
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Degradation Products of Type I Collagen |
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397 | (5) |
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402 | (5) |
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403 | (4) |
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Supramolecular Structure of Cartilage Matrix |
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407 | (1) |
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407 | (1) |
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Light and Electron Micrography |
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408 | (1) |
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Biochemistry of Cartilage |
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409 | (2) |
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Studies of Fibril Structures by X-ray Diffraction |
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411 | (1) |
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Structure of Fibril Fragments Obtained by Mechanical Disruption of Tissue |
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411 | (1) |
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Studies of Collagen Cross-linking in Cartilage Fibrils |
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412 | (1) |
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Reconstitution of Aggregates from Soluble Collagens and other Macromolecules |
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412 | (2) |
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Studies of Transgenic Mice and of Human Genetic Matrix Diseases |
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414 | (1) |
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Correlating Structure With the Biomechanical Role of Articular Cartilage |
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415 | (1) |
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Models of Cartilage Fibril Structure |
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416 | (1) |
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417 | (4) |
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418 | (3) |
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Products of Cartilage Metabolism |
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421 | (1) |
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The Chondrocyte and its Extracellular Matrix |
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422 | (2) |
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Products of Collagen Metabolism |
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424 | (5) |
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Products of Aggrecan Metabolism |
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429 | (5) |
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Products of the Metabolism of other Proteoglycans |
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434 | (1) |
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Products of the Metabolism of Link Protein and Hyaluronan |
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435 | (2) |
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Other Products of Chondrocyte Metabolism |
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437 | (1) |
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438 | (13) |
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439 | (12) |
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Fluid Dynamics of the Joint Space and Trafficking of Matrix Products |
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451 | (1) |
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Interpretation of Marker Data and Strategies for Dealing with Them |
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451 | (5) |
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456 | (1) |
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456 | (1) |
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Transgenic Models of Bone Disease |
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457 | (1) |
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Generation of Mouse Models |
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457 | (3) |
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Transgenic Models in Bone Biology |
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460 | (5) |
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Perspectives and Future Directions |
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465 | (6) |
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465 | (6) |
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Part III Markers of Bone and Cartilage Metabolism |
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The Role of Genetic Variation in Osteoporosis |
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Johannes P.T.M. van Leeuwen |
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471 | (1) |
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Osteoporosis has Genetic Influences |
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471 | (2) |
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Genome-wide Approaches to Find the Genes |
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473 | (3) |
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Association Analysis of Candidate Gene Polymorphisms |
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476 | (2) |
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478 | (2) |
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480 | (2) |
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Osteoporosis Candidate Genes: Collagen Type Iα1 and the Vitamin D Receptor |
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482 | (1) |
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483 | (4) |
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484 | (3) |
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Measurement of Calcium, Phosphate and Magnesium |
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487 | (8) |
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495 | (4) |
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499 | (8) |
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502 | (5) |
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Measurement of Parathyroid Hormone |
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507 | (1) |
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507 | (2) |
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Different Immunometric Assays for the Detection of PTH |
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509 | (1) |
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Primary Hyperparathyroidism |
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510 | (1) |
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Hyperparathyroidism in Renal Osteodystrophy |
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510 | (1) |
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Pseudohypoparathyroidism (PHP) |
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510 | (1) |
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511 | (2) |
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511 | (2) |
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New Horizons for Assessment of Vitamin D Status in Man |
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Measurement of Vitamin D3 (Cholecalciferol) and Vitamin D2 (Ergocalciferol) |
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513 | (1) |
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Measurement of 25-Hydroxyvitamin D |
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513 | (11) |
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Measurement of 1,25-Dihydroxyvitamin D |
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524 | (5) |
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525 | (4) |
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Measurement of Biochemical Markers of Bone Formation |
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529 | (1) |
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529 | (1) |
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Propeptides of Type I Procollagen |
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530 | (3) |
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Total Alkaline Phosphatase |
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533 | (1) |
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Bone Alkaline Phosphatase |
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533 | (2) |
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535 | (2) |
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537 | (4) |
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537 | (4) |
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Measurement of Biochemical Markers of Bone Resorption |
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541 | (2) |
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543 | (10) |
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Non-Collagenous Proteins of the Bone Matrix |
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553 | (2) |
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555 | (10) |
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557 | (8) |
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Variability in the Measurement of Biochemical Markers of Bone Turnover |
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565 | (1) |
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Sources of Pre-Analytical Variability in the Measurement of Biochemical Markers of Bone Turnover |
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566 | (5) |
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Statistical Consideration of Variability |
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571 | (6) |
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577 | (6) |
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578 | (5) |
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Validation of Biochemical Markers of Bone Turnover |
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583 | (1) |
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Validation of Biochemical Markers by Calcium Kinetics |
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584 | (4) |
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Validation of Biochemical Markers by Bone Histomorphometry |
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588 | (4) |
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592 | (3) |
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592 | (3) |
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Genetic Markers of Joint Disease |
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595 | (1) |
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595 | (2) |
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597 | (1) |
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598 | (7) |
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Juvenile Rheumatoid Arthritis |
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605 | (1) |
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606 | (5) |
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606 | (5) |
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Laboratory Assessment of Postmenopausal Osteoporosis |
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611 | (1) |
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612 | (4) |
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Management of Postmenopausal Osteoporosis |
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616 | (8) |
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624 | (5) |
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624 | (5) |
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Monitoring Anabolic Treatment |
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629 | (1) |
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Cellular and Regulatory Mechanisms of the Anabolic Actions of Parathyroid Hormone |
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630 | (1) |
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Pharmacokinetics of Teriparatide in Human Subjects |
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631 | (1) |
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Actions of Parathyroid Hormone to Improve Bone Quality |
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632 | (10) |
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642 | (7) |
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642 | (7) |
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Monitoring of Antiresorptive Therapy |
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649 | (1) |
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Effects of Pretreatment Bone Turnover and Mineral Density on Therapeutic Outcomes |
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650 | (1) |
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The Role of Markers of Bone Turnover in Monitoring Antiresorptive Osteoporosis Therapy |
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651 | (10) |
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Interpretation of Changes in Bone Turnover Markers |
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661 | (10) |
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665 | (6) |
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Age-related Osteoporosis and Skeletal Markers of Bone Turnover |
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671 | (1) |
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Epidemiology and Pathogenesis of Age-Related Osteoporosis-Relationship to Bone Turnover |
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672 | (7) |
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Markers of Bone Turnover and Age-Related Osteoporosis - Clinical Implications |
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679 | (4) |
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683 | (6) |
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683 | (6) |
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Steroid-Induced Osteoporosis |
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689 | (1) |
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689 | (1) |
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689 | (1) |
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690 | (1) |
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Effects of Glucocorticoids on Histological Indices of Bone Turnover |
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691 | (1) |
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Effect of Glucocorticoids on Markers of Bone Turnover |
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692 | (2) |
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Evaluation of Steroid-Treated Patients |
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694 | (1) |
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694 | (7) |
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695 | (6) |
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Transplantation Osteoporosis: Biochemical Correlates of Pathogenesis and Treatment |
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Carolina A. Moreira Kulak |
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701 | (1) |
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702 | (3) |
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705 | (1) |
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706 | (1) |
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706 | (1) |
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Bone Marrow Transplantation |
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707 | (1) |
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Mechanisms of Bone Loss After Transplantation |
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707 | (2) |
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Prevention and Management of Transplantation Osteoporosis |
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709 | (2) |
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711 | (6) |
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711 | (6) |
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Carolina A. Moreira Kulak |
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717 | (1) |
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Hyperthyroidism and Osteoporosis |
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717 | (7) |
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Osteoporosis Secondary to Hypogonadism |
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724 | (6) |
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Anticonvulsant Drugs and Osteoporosis |
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730 | (9) |
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732 | (7) |
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739 | (2) |
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741 | (1) |
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Incidence and Epidemiology |
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742 | (1) |
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Calciopenic Rickets and Osteomalacia |
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743 | (4) |
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Phosphopenic Rickets and Osteomalacia |
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747 | (3) |
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Normal Mineral Rickets and Osteomalacia |
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750 | (5) |
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751 | (4) |
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Assessment of Bone and Joint Diseases: Renal Osteodystrophy |
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755 | (2) |
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Biochemical Assessment of Renal Osteodystrophy |
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757 | (4) |
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Skeletal Imaging in Renal Osteodystrophy |
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761 | (1) |
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762 | (5) |
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762 | (5) |
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Primary Hyperparathyroidism |
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767 | (1) |
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767 | (1) |
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768 | (2) |
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Bone Markers in Primary Hyperparathyroidism |
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770 | (2) |
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Cytokines in Primary Hyperparathyroidism |
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772 | (1) |
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Treatment of Primary Hyperparathyroidism |
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772 | (3) |
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775 | (4) |
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775 | (4) |
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779 | (1) |
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Etiology and Pathogenesis |
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779 | (5) |
|
|
784 | (9) |
|
|
788 | (5) |
|
|
|
|
|
793 | (1) |
|
|
794 | (2) |
|
Use of Markers of Bone Turnover for the Diagnosis of Bone Metastases |
|
|
796 | (6) |
|
Use of Markers of Bone Turnover for the Monitoring of Tumor Bone Disease |
|
|
802 | (4) |
|
Prediction of the Development of Bone Metastases |
|
|
806 | (5) |
|
|
806 | (5) |
|
|
|
|
|
811 | (1) |
|
|
812 | (5) |
|
Osteosclerosis and Hyperostosis |
|
|
817 | (6) |
|
|
823 | (2) |
|
|
825 | (6) |
|
|
826 | (5) |
|
|
|
|
|
|
831 | (1) |
|
|
832 | (1) |
|
|
833 | (1) |
|
|
834 | (1) |
|
|
834 | (1) |
|
Bisphosphonate Therapy in OI |
|
|
835 | (3) |
|
Medical Therapies Other than Bisphosphonates |
|
|
838 | (1) |
|
Potential Future Therapies |
|
|
839 | (1) |
|
|
839 | (4) |
|
|
839 | (4) |
|
Rheumatoid Arthritis and other Inflammatory Joint Pathologies |
|
|
|
|
|
|
843 | (1) |
|
|
843 | (1) |
|
Effects of Joint Inflammation on Skeletal Remodeling |
|
|
844 | (8) |
|
Effects of Joint Inflammation on Cartilage Remodeling |
|
|
852 | (6) |
|
|
858 | (13) |
|
|
858 | (13) |
|
Osteoarthritis and Degenerative Spine Pathologies |
|
|
|
|
|
871 | (1) |
|
|
872 | (1) |
|
|
872 | (1) |
|
|
873 | (1) |
|
Current Diagnostic Procedures |
|
|
873 | (1) |
|
Biochemical Aspects of Osteoarthritis |
|
|
873 | (1) |
|
|
874 | (4) |
|
Markers of Cartilage Metabolism |
|
|
878 | (4) |
|
Spine Degeneration and Markers |
|
|
882 | (1) |
|
|
883 | (1) |
|
|
884 | (1) |
|
|
884 | |