The new edition of this two-volume reference incorporates progress made over the past five years at both the basic science and clinical levels. Important new conceptual themes include insights into skeletal differentiation and regulation, particularly regarding complementary actions of Hedgehog and PTH-related proteins; the RANK/RANK-ligand osteo-protegerin system as a central feature of osteoclast biology; the skeletal phenotypes of mouse gene knockout models; the discovery of a second estradiol receptor which is relatively enriched in bone; and the molecular basis of bisphosphonate action. The 75 chapters include new contributions that discuss major European epidemiological fracture studies, micro-CT assessment of bone architecture, evidence-based analysis of therapy, regulatory considerations for design of osteoporosis trials, skeletal effects of phytoestrogens and selective estradiol receptor modulators, and novel approaches to therapeutics. Illustrated with color and b&w images. Edited by Robert Marcus, David Feldman, and Jennifer Kelsey, all of the Stanford U. School of Medicine. Annotation c. Book News, Inc., Portland, OR (booknews.com)
Osteoporosis is the most comprehensive, authoritative reference on this disease. Some of the topics covered include basic biology, anatomy, physiology, pathophysiology, preclinical issues, experimental medicine, management, and therapeutics. Written by renowned experts in this field, this book is a must-have for the researcher, the academic clinician, or anyone in the field of bone biology.
Key Features
* The source on osteoporosis
* Written by expert investigators in their respective fields
* Each chapter provides timely, comprehensive, and scholarly discussion
* Fully illustrated in color and black & white
* Covers everything from basic anatomy and physiology to diagnosis, management and treatment
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from:Praise for the First Edition "...a textbook focused solely on this condition and encompassing this diversity of research has been lacking. This book does a terrific job of filling the gap... All the chapters are authoritative and include up-to-date references... Osteoporosis is quite comprehensive..." --NEW ENGLAND JOURNAL OF MEDICINE
"The editors have managed to produce a work which is interesting, comprehensive and up-to-date..." --JOURNAL OF BONE AND JOINT SURGERY
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Key Features * The source on osteoporosis * Written by expert investigators in their respective fields * Each chapter provides timely, comprehensive, and scholarly discussion * Fully illustrated in color and black & white * Covers everything from basic anatomy and physiology to diagnosis, management and treatment
Contributors xvii Preface xxiii Part I Introduction to Normal Bone Physiology and Pathophysiology The Bone Organ System: Form and Function Cassandra A. Lee Thomas A. Einhorn Introduction 3(1) Composition and Organization of Bone 4(5) Cellular Control of Bone Homeostasis 9(4) Bone Modeling and Remodeling 13(3) Bone Biomechanics 16(3) Summary 19(2) References 19(2) Osteoblast Biology Jane B. Lian Gary S. Stein Overview 21(1) Embryonic Origins and Signaling Cascades for Osteogenesis 22(5) In Vivo Tissue Level Organization of Osteoblasts: Phenotypic Features and Function 27(8) Cellular Cross-Talk of Osteoblast Lineage Cells: Functions in Calcium Homeostasis, Bone Turnover, and Hematopoiesis 35(3) Osteoblasts in Vitro: Stages in Development of the Osteoblast Phenotype 38(5) Molecular Mechanisms Mediating Progression of Osteoblast Differentiation 43(6) Concluding Remarks 49(24) References 50(23) Osteoclast Biology F. Patrick Ross Steven L. Teitelbaum Introduction 73(1) Osteoclast Morphology 73(4) Origin of Osteoclasts 77(2) Models of Osteoclast Function 79(2) Osteoclast Attachment and Polarization 81(1) Mechanisms of Bone Resorption 81(2) Humoral Regulation of Osteoclastic Bone Resorption 83(6) Diseases of the Osteoclast 89(18) References 95(12) The Biochemistry of Bone Jayashree A. Gokhale Pamela Gehron Robey Adele L. Boskey Introduction 107(3) Collagen 110(7) Glycosaminoglycan-Containing Proteins 117(10) Glycoproteins 127(20) Gla-Containing Proteins 147(4) Other Proteins 151(4) Requirements for Matrix Mineralization 155(1) Pathways of Matrix Mineralization 156(33) References 160(29) Developmental Biology of Bone Anthony M. Reginato WenFang Wang Bjorn R. Olsen Introduction 189(2) Craniofacial Bone Development 191(1) Axial Bone Development 192(1) Limb Bone Development 193(1) Sonic Hedgehog and Indian Hedgehog in Skeletal Development 194(1) Bone Morphogenetic Proteins, Homologues, and Their Antagonists in Skeletal Development 195(2) Fibroblast Growth Factors and Their Receptors in Skeletal Development 197(2) Chondrocyte Differentiation and Endochondral Bone Formation 199(1) Osteoblast Differentiation and Function 200(1) Cell - Matrix Interactions in Skeletal Development 200(3) Summary and Perspectives 203(10) References 204(9) Mouse Genetics as a Tool to Study Bone Development and Physiology Millan S. Patel Gerard Karsenty Introduction 213(1) The Osteoprotegerin Pathway 214(1) Vitamin D Receptor 215(1) Cbfal 215(1) Independence of Bone Resorption from Bone Formation during Bone Remodeling 216(1) Bone Formation Is Centrally Regulated in Vivo 217(4) References 218(3) Parathyroid Hormone and Parathyroid Hormone-Related Protein Robert A. Nissenson Introduction 221(1) Parathyroid Hormone (PTH) 221(5) Parathyroid Hormone-Related Protein (PTHrP) 226(4) Mechanism of Action of PTH and PTHrP 230(17) References 236(11) Calcitonin Ana O. Hoff Gilbert J. Cote Robert F. Gagel Introduction 247(1) Calcitonin Gene Products 247(2) Calcitonin Structure/Function Relationships 249(1) Secretion and Metabolism 250(1) Physiology and Mechanism of Action 250(3) The Calcitonin Receptor Superfamily 253(1) Summary 253(4) References 253(4) Vitamin D: Biology, Action, and Clinical Implications David Feldman Peter J. Malloy Coleman Gross Introduction 257(1) Vitamin D Metabolism 258(3) Pathways of Activation and Inactivation of Vitamin D 261(5) Mechanism of 1,25(OH)2D Action 266(6) Nongenomic Effects of Vitamin D 272(1) Physiology: Regulation of Serum Calcium 273(2) Genetic Disorders and Vitamin D Receptor Polymorphisms 275(5) 1,25(OH)2D3 Analogues with Decreased Calcemic Activity 280(1) Actions of Vitamin D in Classical Target Organs to Regulate Mineral Homeostasis 281(3) Actions of 1,25(OH)2D in Nonclassical Target Organs 284(4) Vitamin D and Osteoporosis 288(17) References 289(16) Regulation of Bone Cell Function by Estrogens Barry S. Komm Peter V. N. Bodine Introduction 305(1) What Is an Estrogen? 305(1) Estrogen Receptors 306(4) ERα and ERβ Knockout Mice 310(1) Estrogens and Bone: Overview 311(1) Estrogen Receptors in Bone Cells 311(4) Estrogenic Responses in Bone Cells 315(12) Estrogen-Related Receptor-α and Osteopontin Gene Expression 327(1) Nongenomic Actions of Estrogens in Bone Cells 327(1) Summary 328(11) References 328(11) Skeletal Biology of Androgens Kristine M. Wiren Eric S. Orwoll Introduction 339(1) The Cellular Biology of the Skeletal Effects of Androgens 339(3) Androgen Actions in Bone 342(4) The Role of Androgen Metabolism 346(2) Animal Studies of the Skeletal Effects of Androgen 348(5) The Role of Aromatization: Effects of Replacement Sex Steroids after Castration 353(1) Gender Specificity in the Actions of Sex Steroids 354(1) The Animal Model of Androgen Resistance 354(1) Summary 354(7) References 355(6) Coupling of Bone Resorption and Formation during Bone Remodeling Thomas J. Martin Gideon A. Rodan Introduction 361(1) Sequence of Cellular Events in Bone Remodeling 362(1) Interaction of Osteoblast Lineage Cells with Osteoclasts 363(1) Similarities between Bone Remodeling and Inflammation 363(1) Factors Proposed to Mediate the Coupling of Bone Formation to Bone Resportion 364(1) Bone Mass Homeostasis 365(1) Role of Mechanical Function (Strain) in the Coupling of Bone Resorption to Bone Formation 366(1) Integrated View of the Coupling of Bone Resorption and Bone Formation 367(6) References 368(5) Cytokines and Bone Remodeling Gregory R. Mundy Babatunde Oyajobi Kathy Traianedes Sarah Dallas Di Chen Introduction 373(1) Evidence for a Role of Cytokines in Osteoclastic Bone Resorption 374(1) The Osteoclast as a Cell Source of Cytokines Involved in Osteoclastic Resorption 375(1) The Osteoblast as a Cell Source of Cytokines Involved in Osteoclastic Resorption 376(1) RANK Ligand and Its Signaling Receptor, RANK 376(2) Osteoprotegerin 378(2) Macrophage-Colony-Stimulating Factor and Its Signaling Receptor, c-fms 380(1) Interleukin (IL)-1 and IL-1 Signaling in Osteoclast-like Cells 380(2) Tumor Necrosis Factor 382(1) Interleukin-6 382(1) Vascular Endothelial Growth Factor 383(1) IL-15, IL-17, and IL-18 383(1) Arachidonic Acid Metabolites: Prostaglandins and Leukotrienes 384(3) Transforming Growth Factor-β 387(3) Bone Morphogenetic Proteins 390(2) Conclusion 392(13) References 393(12) Bone Growth Factors Xuezhong Qin Reinhard Gysin Subburaman Mohan David J. Baylink Introduction 405(1) Bone Growth Factors 405(17) Conclusions 422(11) References 422(11) Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis A. M. Parfitt Introduction 433(1) Skeletal Heterogeneity 434(2) Purposes of Bone Remodeling 436(3) Implications for Understanding Osteoporosis 439(10) References 444(5) Basic Biology of Bisphosphonates H. Fleisch Introduction 449(1) Chemistry 449(2) Actions 451(8) Pharmacokinetics 459(2) Animal Toxicology 461(10) References 462(9) Part II Structure and Biomechanics Skeletal Development: Mechanical Consequences of Growth, Aging, and Disease Marjolein C. H. van der Meulen Dennis R. Carter Gary S. Beaupe Developmental Mechanics in Skeletogenesis 471(2) Mechanical Regulation of Bone Biology 473(2) Mechanobiologic Self-Design of Bones 475(10) Adaptational Mechanics in Aging and Disease 485(4) References 486(3) Inhibition of Osteopenia by Biophysical Intervention Clinton T. Rubin Stefan Judex Kenneth J. McLeod Xi-Xian Qin Introduction 489(1) Wolffs Law of Bone Adaption 490(1) Structural Demands on the Vertebrate Skeleton 491(3) Modulation of Bone Tissue by Biophysical Stimuli 494(6) Attenuation of Wolffs Law by Systemic Disorders 500(2) Clinical Application of Biophysical Stimuli 502(3) Summary 505(4) References 505(4) Biomechanics of Age-Related Fractures Mary L. Bouxsein Introduction 509(2) Biomechanics of Bone: Basic Concepts and Age-Related Changes 511(6) Biomechanics of Hip Fractures 517(4) Biomechanics of Vertebral Fractures 521(4) Summary and Clinical Implications 525(10) References 526(9) Part III Epidemiology and Risk Factors Introduction to Epidemiologic Methods Jennifer L. Kelsey MaryFran Sowers Introduction 535(1) Descriptive and Analytic Studies 536(1) Study Designs 536(6) Some Useful Epidemiologic Concepts 542(1) Some Frequently Used Statistics 542(2) Criteria for Deciding Whether an Association Is Causal 544(1) Sample Size Considerations 545(1) Measurement Error 546(5) Measuring Diet and Bone Turnover Status as Examples of Measurement Issues 551(2) Conclusions 553(4) References 553(4) Magnitude and Impact of Osteoporosis and Fractures L. Joseph Melton III Cyrus Cooper Introduction 557(1) Magnitude of the Problem 557(2) Fracture Epidemiology 559(3) Impact of Osteoporotic Fractures 562(1) Future Projections 563(1) Conclusions 564(5) References 565(4) Race, Ethnicity, and Osteoporosis Marie Luz Villa Lorene Nelson Dorothy Nelson We Are All Individuals 569(1) Defining Terms 569(1) Ethnoepidemiology of Osteoporosis 570(4) Racial and Ethnic Influences on Risk for Osteoporosis 574(5) Summary 579(6) References 580(5) Epidemiology of Osteoporotic Fractures in Europe Chris de Laet Jonathan Reeve Introduction 585(1) Hip Fractures 586(3) Vertebral Fractures 589(6) General Conclusions 595(4) References 595(4) Bone Mineral Acquisition in Utero, during Infancy, and throughout Childhood Bonny L. Specker Ran Namgung Reginald C. Tsang Introduction 599(1) Measurement of Bone Mass in Infants and Children 599(2) Bone Acquisition in Utero 601(5) Bone Acquisition in Preterm Infants 606(3) Bone Mineral Acquisition in Term Infants and Children 609(5) Summary 614(7) References 614(7) Bone Acquisition in Adolescence Jean-Philippe Bonjour Rene Rizzoli Introduction 621(1) Measurement of Bone Mass Development 621(1) Bone Mass Gain during Puberty 622(4) Calcium-Phosphate Metabolism during Puberty 626(1) Determinants of Bone Mass Gain 627(12) References 633(6) Genetics and Genomics of Osteoporosis Andre G. Uitterlinden Johannes P.T.M. van Leeuwen Huibert A. P. Pols Introduction 639(2) Top-Down and Bottom-Up Genomic Approaches 641(5) Considerations and Complicating Factors 646(2) The Map of Osteoporosis Genes 648(15) Applications and Prospects 663(6) References 664(5) Nutrition and Risk for Osteoporosis Robert P. Heaney Introduction 669(2) Problems in the Investigation of the Effects of Nutrition on Bone 671(3) The Notion of a Nutrient Requirement 674(1) The Natural Intake of Calcium and Vitamin D 675(1) Calcium 676(14) Vitamin D 690(1) Vitamin K 691(1) Other Essential Nutrients 692(9) References 694(7) Physical Activity and Osteoporosis Belinda R. Beck Janet Shaw Christine M. Snow Introduction 701(1) Design Considerations 701(1) Effects of Loading Bone 702(3) Physical Activity and Bone 705(6) Hormone Response to Chronic Exercise 711(1) Meta-analyses and Reviews 712(1) Falling and Fracture 712(1) Therapeutic Suggestions 713(1) References 714(105) Premenopausal Reproductive and Hormonal Characteristics and the Risk for Osteoporosis MaryFran Sowers Introduction 721(1) Pregnancy 722(1) Age at First Pregnancy 723(1) Parity and Nulliparity 724(1) Lactation 725(2) Ovarian Activity or Menstrual Cycle Characteristics and Bone Mass 727(1) Dysfunctional Ovulation 728(2) Oral Contraceptive Use 730(2) Progestin-Injectible Contraceptives 732(1) Oophorectomy 733(1) Summary and Implications 734(7) References 734(7) Postmenopausal Endogenous and Exogenous Hormones, Degree of Obesity, Thiazide Diuretics, and Risk of Osteoporosis Jane A. Cauley Loran M. Salamone Introduction 741(1) Thiazide Diuretics 741(8) Exogenous Estrogen 749(5) Endogenous Estrogen, Bone Mass, and Fractures 754(2) Obesity 756(7) Overall Summary 763(8) References 763(8) The Effects of Tobacco and Alcohol Use on Bone Ego Seeman Introduction 771(1) Tobacco and Bone 772(10) Alcohol and Bone 782(8) Conclusions and Questions 790(5) References 791(4) Falls as Risk Factors for Fractures Ann V. Schwartz Elizabeth Capezuti Jeane Ann Grisso Introduction 795(1) Risk Factors for Falls 796(2) Risk Factors for a Fall-Related Injury 798(2) Prevention of Falls and Fall-Related Fractures 800(3) Summary and Directions for Future Research 803(6) References 803(6) Assessing Fracture Risk Charles W. Slemenda C. Conrad Johnston Siu L. Hui Introduction 809(1) Skeletal Elements of Fracture Risk 810(2) Nonskeletal Elements of Fracture Risk Assessment 812(1) Measuring Bone Loss for Risk Assessment: Necessary or Useful? 813(1) Monitoring Bone Mass 814(1) The Expression of Risk 815(1) Summary 816(3) References 816(3) Outcomes of Osteoporotic Fractures Gail A. Greendale Elizabeth Barrett-Conner Introduction 819(1) Definitions of Functional Outcomes Related to Fracture 819(1) Outcomes of Wrist Fractures 820(1) Outcomes of Vertebral Fractures 821(5) Outcomes of Hip Fractures 826(2) Conclusions 828 References 828 Part IV Pathophysiology The Nature of Osteoporosis Robert Marcus Sharmilla Majumder Defining Osteoporosis 3(2) The Nature of Osteoporotic Bone 5(10) Conclusions 15(4) References 16(3) Local and Systemic Factors in the Pathogenesis of Osteoporosis Lawrence R. Raisz Introduction 19(1) Limited Role of Systemic Hormones 20(1) Local Factors 20(1) Cytokines 21(1) Prostaglandins 21(1) Growth Factors 22(1) Colony-Stimulating Factors 22(1) Further Considerations of Interactions of Systemic Hormones and Mediators 22(1) Conclusions 23(6) References 24(5) Animal Models for in Vivo Experimentation in Osteoporosis Research Donald B. Kimmel Introduction 29(1) A Perspective on in Vivo Animal Experimentation 30(1) Criteria for Animal Models in Osteoporosis: A Time for Compromise 30(1) The Criteria 31(2) Animal Models for Human Osteoporosis 33(16) References 39(10) The Type I/Type II Model for Involutional Osteoporosis: Update and Modification Based on New Observations B. Lawrence Riggs Sundeep Khosla L. Joseph Melton III Introduction 49(2) Validating Evidence 51(4) Tests of Validity 55(1) Conceptual Problems 55(2) Summary and Conclusions 57(2) References 57(2) Bone Remodeling Findings in Osteoporosis Robert R. Recker M. Janet Barger-Lux Introduction 59(1) Background 59(6) Histomorphometric Findings in Osteoporosis 65(3) Bone Remodeling at the Whole-Organisms Level 68(1) Summary 68(3) References 69(2) The Role of Parathyroid Hormone and Vitamin D in the Pathogenesis of Osteoporosis John P. Bilezikian Shonni J. Silverberg Introduction 71(1) Vitamin D and Osteoporosis 72(3) Parathyroid Function in Osteoporosis 75(5) Summary 80(5) References 80(5) Postmenopasual Osteoporosis: How the Hormonal Changes of Menopause Cause Bone Loss Roberto Pacifici Steroid Biosynthesis and Menopause 85(1) Mechanism of Action of Estrogen in Bone 86(10) Summary and Conclusions 96(7) References 97(6) Osteoporosis in Men: Epidemiology, Pathophysiology, and Clinical Characterization Eric S. Orwoll Robert F. Klein Introduction 103(1) Fractures in Men 103(4) The Major Determinants of Skeletal Health in Men 107(6) Osteoporosis 113(8) The Evaluation of Osteoporosis in Men 121(4) Therapy 125(6) Hypogonadism 131(4) Alcoholism 135(1) Tobacco 135(1) Renal Stone Disease 135(16) References 135(16) Osteoporosis in Childhood and Adolescence Laura K. Bachrach Introduction 151(2) Anorexia Nervosa 153(1) Reproductive Disorders 154(2) Other Endocrine Disorders 156(3) Systemic Disease 159(2) Idiopathic Juvenile Osteoporosis 161(1) Summary and Future Directions 162(7) References 162(7) Glucocorticoid-Induced Osteoporosis: Basic Pathological Mechanisms, Clinical Features, and Management in the New Millennium Gary M. Leong Jacqueline R. Center N. Kathryn Henderson John A. Eisman Introduction 169(1) The Scope of the Problem and Economic Considerations 170(1) Effect of Glucocorticoids on Bone Density and Fracture Incidence 170(1) Glucocorticoid-Induced Muscle Weakness 171(1) Glucocorticoids: Methods of Administration and Dosage Effects 171(1) The Pathogenesis and Molecular Basis of Glucocorticoid Action on Bone Metabolism and Development 172(7) Glucocorticoids and Calcium Homeostasis 179(1) Treatment Options 180(5) Treatment and Fracture Outcomes 185(1) Management of Glucocorticoid-Induced Osteoporosis in Children 185(10) References 185(10) Familial Osteoporosis Alan L. Burshell Steven R. Smith Introduction 195(1) Importance of and Obstacles to the Study of Familial Osteoporosis 195(1) Genetic Analysis of Complex Traits 196(1) Animal Models 197(1) Selection of Families 198(1) Epidemiologic Data 198(3) Polymorphisms and Bone Mineral Density 201(1) Collagen as a Candidate Gene for Familial Osteoporosis 201(3) Conclusions 204(3) References 204(3) Immobilization Osteopenia B. Jenny Kiratli Overview 207(1) Clinical Conditions of Immobilization 208(1) Evidence of Skeletal Response to Immobilization 209(6) Relevant Sequelae in Spinal Cord Injury Patients 215(6) Intervention Attempts 221(3) Clinical Relevance 224(5) References 224(5) Thyroid Hormone and the Skeleton Daniel Baran Introduction 229(1) Thyroid Hormone and Skeletal Growth and Maturation 229(1) Thyroid Hormone and Mineral Metabolism 230(1) Thyroid Hormone and Skeletal Metabolism 230(1) Bone Mass and Fracture Risk in Thyroid Disease 231(1) Prevention of Thyroid Hormone-Induced Bone Loss 231(6) References 232(5) Osteoporosis in Gastrointestinal, Pancreatic, and Hepatic Diseases Daniel D. Bikle Physiologic Considerations 237(3) Gastrointestinal Diseases 240(5) Hepatic Diseases 245(4) Bone Disease Complicating Therapy 249(10) References 251(8) Primary Hyperparathyroidism and Hyperparathyroid Bone Disease Lorraine A. Fitzpatrick Hunter Health III Introduction 259(1) The Actions of Parathyroid Hormone on Bone 259(2) PTH Secretion in Primary Hyperparathyroidism 261(1) Clinical Manifestations of Bone Disease in Primary Hyperparathyroidism 261(4) Effects of Therapy on Bone Mass in Primary Hyperparathyroidism 265(1) Summary and Conclusions 266(5) References 266(5) Osteogenesis Imperfecta and Other Defects of Bone Development as Occasional Causes of Adult Osteoporosis Jay R. Shapiro Scope of the Problem 271(1) Osteogenesis Imperfecta as a Cause of Adult Osteoporosis 272(11) Histology of Bone in Osteoporosis Imperfecta 283(7) Osteoporosis in the Heritable Disorders of Connective Tissue 290(4) Osteoporosis in Inherited Hematologic Disorders 294(1) Osteoporosis in Inherited Hepatic Disease 295(8) References 295(8) Osteoporosis Secondary to Illnesses and Medications Adina Schneider Elizabeth Shane Introduction 303(1) Hematologic Disorders 303(6) Metabolic Disorders 309(5) Medications 314(13) References 319(8) Transplantation Osteoporosis Sol Epstein Elizabeth Shane Immunosuppression and Osteoporosis 327(1) Immunosuppressive Agents 328(2) Clinical Impact of Transplantation on Bone 330(3) Evaluation of Candidates for Transplanation 333(1) Management of Transplanation Osteoporosis 334(7) References 337(4) Osteoporosis Associated with Pregnancy Lynn Kohlmeier Robert Marcus Introduction 341(1) Calcium Homeostasis during Pregnancy and Lactation 341(1) Osteoporosis Associated with Pregnancy 342(3) Osteoporosis Associated with Heparin Therapy during Pregnancy 345(1) Osteoporosis Associated with Magnesium Sulfate Therapy during Pregnacy 346(1) Paradoxical Bone Mineralization in Twin-to-Twin Transfusion Syndrome 346(5) References 346(5) Osteoporosis Associated with Rheumatologic Disorders Steven R. Goldring Introduction 351(1) Rheumatoid Arthritis 351(5) Juvenile Rheumatoid Arthiritis 356(1) Seronegative Spondyloarthropathies 356(2) Systemic Lupus Erythematosus 358(5) References 359(4) Oral Bone Loss and Systemic Osteopenia Marjorie K. Jeffcoat Michael S. Reddy Arthur A. DeCarlo Introduction 363(2) Diagnosis 365(3) Risk Factors for Intraoral Bone Loss 368(3) Patterns of Progression of Oral Bone Loss 371(1) Residual Ridge Resorption 372(1) Etiologic and Host Response Factors in Oral Bone Resorption 372(4) Oral Bone Loss and Systemic Osteopenia: Are They Related? 376(1) Treatment 377(1) Summary 378(7) References 378(7) Localized Osteoporosis D. J. Schurman W. J. Maloney R. L. Smith Introduction 385(1) Mechanical Stress and Normal Bone Architecture 386(2) Localized Osteoporosis: Generalizations 388(1) Localized Osteoporosis and Fracture 388(1) Internal Fixation Devices 389(2) Inflammatory Disease-Associated Localized Osteoporosis 391(1) Reflex Sympathetic Dystrophy 391(1) Transient Osteoporosis of the Hip 391(1) Total Hip Replacement 392(2) Prosthetic Design 394(1) Immobilization Osteoporosis: Animal Studies of Localized Bone Loss 395(1) Aging 396(1) Hormones and Drugs 396(1) Local Cellular Mechanisms 397(1) Summary 397(6) References 397(6) Part V Evaluation and Management Evaluation of the Patient with Osteoporosis or at Risk for Osteoporosis Michael Kleerekoper Introduction 403(1) The Decision to Measure BMD 403(2) What BMD to Measure 405(1) The Evaluation of the Patient with Low BMD 406(2) Summary and Conclusions 408(3) References 408(3) Imaging of Osteoporosis Michael Jergas Harry K. Genant Introduction 411(1) Principal Radiographic Findings in Osteopenia and Osteoporosis 411(3) Diseases Characterized by Generalized Osteopenia 414(8) Regional Osteoporosis 422(11) References 428(5) Clinical Use of Bone Densitometry Kenneth G. Faulkner Densitometry Techniques 433(386) Basic Principles of Densitometry 440(2) Performing Densitometry Measurments with DXA 442(6) Monitoring the DXA Scanner 448(3) Uses of Bone Densitometry 451(6) Conclusions 457(2) References 457(2) Biochemical Markers of Bone Turnover in Osteoporosis Patrick Garnero Pierre D. Delmas Introduction 459(1) Biochemical Markers of Bone Formation 460(1) Biochemical Markers of Bone Resorption 461(7) Clinical Uses of Bone Markers in Osteoporosis 468(11) References 473(6) Osteoporosis and Its Nonskeletal Consequences: Their Impact on Treatment Decisions Deborah T. Gold Kenneth W. Lyles Kathy M. Shipp Marc K. Drezner Introduction 479(1) Primary Nonskeletal Outcomes of Osteoporosis 480(1) Other Nonskeletal Consequences of Osteoporosis 481(2) Conclusions 483(2) References 483(2) An Orthopedic Perspective of Osteoporosis Michael H. Heggeness Kenneth B. Mathis Introduction 485(1) Biomechanics 485(1) Discussion of Specific Injuries 486(11) Prevention of Fracture 497(4) References 498(3) Clinical Use of Bone Biopsy P. Chavassieux M. Arlot P. J. Meunier Introduction 501(1) Methodology 501(4) Indications for Bone Biopsy 505(3) Conclusions 508(5) References 508(5) PART VI Pharmacology and Therapeutics Design Considerations for Clinical Investigations of Osteoporosis Robert P. Heaney Background: Inference from Phenomena Subject to Variation 513(1) Types of Investigational Designs 514(1) Principal Types of Bias with Various Designs 515(6) When Controlled Trials and Observational Studies Disagree 521(1) Design Alternatives 522(2) Design Issues of Special Relevance to Investigation of Bone 524(7) Burden of Proof and the Null Hypothesis 531(2) References 532(1) Development and Evaluation of New Drugs for Osteoporosis Henry Bone Introduction 533(1) Selection of Drugs for Clinical Development 533(1) Role of Preclinical Testing 534(1) Relationship of Bone Mass to Strength 534(1) Animal Testing 534(2) Human Testing 536(3) References 538(1) Evidence-Based Decision Making in Osteoporosis Ann B. Cranney Gordon H. Guyatt Introduction 539(1) Clinical Decision Making in Osteoporosis 539(1) Collecting the Evidence 540(1) Strength of the Evidence/Study Design 540(1) Magnitude of the Treatment Effect 541(1) Osteoporosis Outcomes and Their Relevance to Patients 542(1) Threshold Level of Treatment 543(1) Consideration of Patient Values 543(1) Conclusions 543(2) References 543(2) The Role of Calcium in the Treatment of Osteoporosis Bess Dawson-Hughes Calcium Absorption 545(2) Calcium and Bone 547(2) Calcium Sources 549(4) References 551(2) Vitamin D and Its Metabolites in the Management of Osteoporosis Ian R. Reid Introduction 553(1) Vitamin D in the Pathogenesis of Osteoporosis 554(1) Animal Models 555(1) Postmenopausal Osteoporosis 556(15) Other Osteoporoses 571(1) Conclusions 571(6) References 571(6) Estrogens and Osteoporosis Robert Lindsay Felicia Cosman Introduction 577(1) Epidemiology 577(1) Pathophysiology 578(7) The Effects of Estrogen Intervention 585(10) Summary 595(8) References 595(8) Selective Estrogen Receptor Modulators (SERMs) Ethel S. Siris Douglas B. Muchmore Introduction 603(1) Mechanism of Action of SERMs 603(4) Clinical Application of SERMs 607(14) References 616(5) Phytoestrogen and Other Phytochemical Effects on Bone Richard Prince Introduction 621(1) Definition 622(1) Classification and Biological Action of Phytoestrogens 622(1) Concentration in Plants 623(1) Bioavailability 624(1) The Epidemiology of Phytoestrogens as Nutraceutical Agents 624(1) Specific Phytoestrogens in Relation to Bone and Mineral Physiology and Anatomy 624(3) Conclusions 627(4) References 627(4) Bisphosphonates in the Management of Postmenopausal Osteoporosis Socrates E. papapoulous Introduction 631(1) Pharmacokinetics-Pharmacodynamics 632(2) Treatment Protocols 634(2) Effects on Bone Mineral Density 636(1) Antifracture Efficacy 636(4) Special Issues of Bisphosphonate Therapy and Unanswered Questions 640(2) Long-Term Effects on Bone Metabolism 642(2) Adverse Effects 644(2) Conclusions 646(5) References 646(5) Calcitonin for Treatment of Osteoporosis Roberto Civitelli Introduction 651(1) Clinical Efficacy in Osteoporotic Syndromes 651(11) Clinical Pharmacology 662(4) Analgesic Action 666(2) Future Directions 668(7) References 668(7) Fluoride Therapy for Osteoporosis K.-H. William Lau David J. Baylink Introduction 675(1) Molecular Mechanisms of Action of Fluoride on Bone Cells 675(3) Pharmacokinetics and Metabolism of Fluoride 678(1) Relevance of Serum Fluoride Concentrations to Biological Responses 679(2) Skeletal Responses to Fluoride Therapy 681(4) Side Effects of Fluoride Therapy 685(2) Clinical Efficacy of Fluoride Therapy 687(4) Strategies for Improving Fluoride Therapy 691(2) Conclusion 693(6) References 694(5) A New Perspective on Fluoride Therapy Charles Y. C. Pak Introduction 699(1) Pharmacokinetic Studies 699(3) Long-Term Randomized Clinical Trials 702(3) Analysis of Spinal Fracture Data from 12 Trials According to Relative Fluoride Absorption 705(1) Analysis of Appendicular Fracture Data from 12 Trials According to Relative Fluoride Absorption 705(1) Discussion 706(3) References 708(1) Androgens and Androgenic Progestins Sundeep Khosla Introduction 709(1) Classification of Androgens and Progestins 709(3) Androgens 712(5) Progesterone and Androgenic Progestins 717(2) Tibolone 719(1) Conclusions 719(6) References 719(6) Treatment with PTH Peptides Lis Mosekilde Jonathan Reeve Rationale for the Treatment of Osteoporosis with Parathyroid Peptides or Other Anabolic Agents 725(1) Historical Background 726(1) Biological Basis of the Actions of Parathyroid Peptides 727(1) Effects of PTH in Animal Models 727(8) Clinical Studies 735(6) Conclusions 741(6) References 742(5) Growth Hormone, Insulin-like Growth Factors: Potential Applications and Limitations in the Management of Osteoporosis Christian Wuster Clifford Rosen Introduction 747(1) Physiology of Growth-Hormone-Releasing Hormone (GHRH)-GH-IGF-I 748(4) The Role of GH-IGF-I in Skeletal Physiology 752(1) Pathophysiology of Osteoporosis: Role of GH-IGFs 753(2) Growth Hormone Therapy for Osteoporosis 755(4) IGF-I for the Treatment of Osteoporosis 759(3) Summary 762(7) References 763(6) New Approaches to Osteoporosis Therapeutics S. Aubrey Stoch Michael Chorev Michael Rosenblatt Introduction 769(1) Parathyroid Hormone and Parathyroid Hormone-Related Protein 770(6) Calcium Receptor Antagonists 776(3) Stimulation of Bone Formation and Inhibition of Resorption by Statins 779(1) Inhibition of Bone Resorption with αvβ3 Integrin Antagonists 780(5) Osteoprotegerin 785(7) Cathepsin K 792(4) Inhibitors of Src in Osteoporosis 796(4) Combined Therapies 800(6) Summary 806(13) References 806(13) Index 819
Dr. Marcus is Professor-Emeritus, Stanford University, where he served on the full-time medical faculty for almost 25 years, before joining the Emeritus faculty in 2001. At Stanford, he was located at the Veterans Affairs Medical Center, Palo Alto California, where he served as Director of the Aging Study Unit of the Geriatrics Research, Education, & Clinical Center from 1982-2001. Dr. Marcus enjoyed a long career as a clinical investigator in the fields of bone and mineral metabolism and osteoporosis medicine. His own research interests included diagnosis and therapy of primary hyperpara-thyroidism, interactions of the parathyroid-vitamin D axis with estrogen, age-related changes in the growth hormone-IGF axis, effects of growth hormone replacement for older men and women, metabolic and musculoskeletal effects of resistance exercise in older men and women, adolescent bone acquisition, and osteoporosis therapeutics. Dr. Marcus laboratory was a study site for many of the pivotal clinical trials in the osteoporosis field. These include the NIH Post-menopausal Estrogen/Progestin Interventions Trial (PEPI), Mercks Fracture Intervention Trial (FIT), Lillys Multiple Outcomes of Raloxifene Intervention (MORE), and Lillys registration trial of recombinant PTH(1-34) in the treatment of postmenopausal women with osteoporosis. In 2001. Dr. Marcus joined the US Affiliate of Eli Lilly & Company to support Lillys program in Osteoporosis and Skeletal Medicine. From 2003 until his retirement from Lilly in 2008, Dr. Marcus was the lead physician for the Forteo team at Lilly. He has published more than 150 research papers, editorials, and reviews. Dr. Marcus served as President of the American Society for Bone & Mineral Research in 2000-2001.
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