Osteoporosis, Two-Volume Set

Front Cover

Osteoporosis

Copyright Page

Contents

Contributors

Preface

Part I: Introduction

Chapter 1: The Bone Organ System: Form and Function

I. Introduction

II. Composition and Organization of Bone

III. Cellular Components of Bone

IV. Bone Homeostasis

V. Bone Mechanics

VI. Summary

References

Chapter 2: The Nature of Osteoporosis

I. Defining Osteoporosis

II. Material and Structural Basis of Skeletal Fragility

III. Conclusions

References

Chapter 3: The Economics of Osteoporosis

I. Introduction

II. Cost of Illness Studies: Characterizing the Magnitude of the Health Problem

III. Cost-Effectiveness Analyses: Identifying Efficient Osteoporosis Care Strategies

IV. Future Research Directions

Acknowledgments

References

Chapter 4: Reflections on Osteoporosis

I. Introduction

II. Definition

III. Diagnosis

IV. Fragility Fractures

V. Bone Density and Fracture Risk

VI. Pathogenesis

VII. Prevention

VIII. Treatment

IX. Conclusions

References

Chapter 5: Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis

I. Introduction

II. Skeletal Heterogeneity

III. The Purposes of Bone Remodeling

IV. Implications for Understanding Osteoporosis

References

Part II: Basic Science of Bone Biology

Chapter 6: Osteoblast Biology

I. Overview

II. Embryonic Development of the Osteoblast Phenotype: Lessons for Bone Formation in the Postnatal Skeleton

III. Development Sequence of Osteoblast Phenotype Development

IV. Phenotype Properties of Osteogenic Lineage Cells

V. Molecular Mechanisms Mediating Progression of Osteoblast Growth and Differentiation

VI. Conclusion

Acknowledgments

References

Chapter 7: Osteoclast Biology

I. Introduction

II. Key Osteoclast Differentiation Pathways

III. The Fully Differentiated Osteoclast: Mechanisms of Bone Degradation

IV. Bone Resorption Coordinated by Intermediate Proteins

V. Osteoclast Death

VI. Mechanistic Approaches to Modification of Osteoclastic Activity In Vivo

VII. Regulation of Osteoclastic Differentiation and Activity In Vivo

VIII. Interaction of Hormonal and Local Signals with Osteoclast Activity

IX. Diseases with Altered Bone Resorption

References

Chapter 8: Osteocytes

I. Introduction

II. Osteocyte Ontogeny

III. Osteoid-Osteocytes

IV. Osteocyte Selective Genes/Proteins and their Potential Functions

V. Morphology of Osteocytes: Lacunocanalicular System and Dendrite Formation

VI. Osteocyte Cell Models

VII. Mechanisms and Response of Osteocytes to Mechanical Forces

VIII. Osteocyte Signals for Bone Formation

IX. Osteocyte Signals for Bone Resorption

X. Osteocyte Apoptosis

XI. Osteocyte Modification of their Microenvironment

XII. Osteocyte Density

XIII. Role of Gap Junctions and Hemichannels in Osteocyte Communication

XIV. Osteocytes in the Embryonic and the Adult Skeleton

XV. The Implications of Osteocyte Biology for Bone Disease

XVI. Conclusions

Acknowledgment

References

Chapter 9: The Regulatory Role of Matrix Proteins in Mineralization of Bone

I. Introduction

II. Collageneous Proteins

III. Intermediate Cartilage Matrix

IV. Bone-Enriched Matrix Proteins

V. The Mineralization of Bone Matrix

Acknowledgments

References

Chapter 10: Development of the Skeleton

I. Introduction

II. Patterning the Skeleton

III. Endochondral Bone Formation

IV. Intramembranous Bone Formation

References

Chapter 11: Mouse Genetics as a Tool to Study Bone Development and Physiology

I. Introduction: Historical Perspective and Significance

II. Introduction To Mouse Skeletal Physiology

III. Inbred Strains of Mice

IV. Recombinant Inbred strains

V. Congenic Strains

VI. Recombinant Congenic Strains

VII. Summary

References

Chapter 12: Parathyroid Hormone and Parathyroid Hormone-Related Protein

I. Introduction

II. Secretion of Parathyroid Hormone

III. Metabolism of Parathyroid Hormone

IV. Bone Resorbing Action of Parathyroid Hormone

V. Effects of Parathyroid Hormone on Bone Formation

VI. Renal Actions of Parathyroid Hormone

VII. Parathyroid Hormone-Related Protein as a Mediator of Malignancy-Associated Hypercalcemia

VIII. Physiological Roles of Parathyroid Hormone-Related Protein

IX. Mechanism of Action of Parathyroid Hormone and Parathyroid Hormone-Related Protein

Acknowledgments

References

Chapter 13: Vitamin D: Biology, Action, and Clinical Implications

I. Introduction

II. Vitamin D Synthesis and Metabolism

III. Pathways of Activation and Inactivation of Vitamin D

IV. Mechanism of 1,25(OH)2 D Action

V. Nongenomic Actions of Vitamin D

VI. Physiology: Regulation of Serum Calcium

VII. Genetic Disorders

VIII. 1,25(OH)2 D3 Analogs with Decreased Calcemic Activity

IX. Actions of Vitamin D in Classical Target Organs to Regulate Mineral Homeostasis

X. Actions of 1,25(OH)2D in Nonclassical Target Organs

XI. Vitamin D and Osteoporosis

References

Chapter 14: Regulation of Bone Cell Function by Estrogens

I. Introduction

II. What is an Estrogen?

III. Estrogen Receptors

IV. ERalpha and ERbeta Knockout Mice (ERKO and ßERKO)

V. Estrogens and Bone

VI. Estrogen Receptors in Bone Cells

VII. Estrogenic Responses in Bone Cells

VII. Estrogen-Related Receptor-alpha and Osteopontin Gene Expression

IX. Nongenomic Actions of Estrogens in Bone Cells

X. Conclusion

References

Chapter 15 Androgens and Skeletal Biology: Basic Mechanisms

I. Introduction

II. Androgens and the Role of Androgen Metabolism

III. Cellular Biology of the Androgen Receptor in the Skeleton

IV. The Consequences of Androgen Action in Bone Cells

V. The Skeletal Effects of Androgen: Animal Studies

VI. Animal Models of Altered Androgen Responsiveness

VII. Effects on the Periosteum: The Role of Androgen Receptor versus Aromatization of Testosterone

VIII. Summary

References

Chapter 16: Phosphatonins

I. Introduction

II. Phosphorus Homeostasis

III. Phosphatonins

IV. Fibroblast Growth Factor 23

V. Secreted Frizzled-Related Protein 4

VI. Matrix Extracellular Phosphoglycoprotein

VII. Fibroblast Growth Factor 7

VIII. Summary

References

Chapter 17: Wnt Signaling in Bone

I. Wnts

II. The Wnt/beta-Catenin Signaling Pathway

III. Other Wnt Pathways

IV. Mutations in Wnt Pathway Components and Altered Bone Mass

V. Wnt Signaling and Bone Cell Function

VI. Wnt Signaling and the Bone Response to Mechanical Loading

VII. Conclusions and Future Directions

References

Chapter 18: Cytokines and Bone Remodeling

I. Introduction

II. Evidence for a Role of Cytokines in Osteoclastic Bone Resorption

III. The Osteoclast as a Cell Source of Cytokines Involved in Osteoclastic Resorption

IV. The Osteoblast as a Cell Source of Cytokines Involved in Osteoclastic Resorption

V. Rank Ligand and Its Signaling Receptor, RANK

VI. Osteoprotegerin

VII. Macrophage–Colony-Stimulating Factor and Its Receptor, C-fms

VIII. Vascular Endothelial Growth Factor

IX. Tumor Necrosis Factor

X. Interleukin-6 (IL-6)

XI. Interleukin-15 (IL-15), Interleukin-17 (IL-17), and Interleukin-1 8 (IL-18)

XII. Bone Morphogenetic Proteins

XIII. Hedgehog (Hh) Signaling Molecules

XIV. Sclerostin

XV. Parathyroid Hormone-Related Peptide (Pthrp)

XVI. Neuronal Regulation of Bone Remodeling

XVII. Conclusion

References

Chapter 19: Skeletal Growth Factors

I. Introduction

II. Platelet-Derived Growth Factor

III. Vascular Endothelial Growth Factor

IV. Fibroblast Growth Factor

V. Transforming Growth Factor Beta

VI. Bone Morphogenetic Protein

VII. Insulin-Like Growth Factor

VIII. Insulin-Like Growth Factor Binding Proteins

IX. Hepatocyte Growth Factor

Acknowledgments

References

Chapter 20: Intercellular Communication during Bone Remodeling

I. Introduction

II. Sequence of Cellular Events in Bone Remodeling

III. Cell Interactions Early in Remodeling

IV. Interaction of Osteoblast Lineage Cells with Osteoclasts

V. Factors Proposed to Mediate the Coupling of Bone Formation to Resorption

VI. Osteoclast Products in the Coupling Process

VII. Similarities between Bone Remodeling and Inflammation

VIII. Bone Mass Homeostasis

IX. The Role of Mechanical Function (Strain) in the Coupling of Bone Resorption to Bone Formation

X. Integrated View of the Coupling of Bone Resorption and Bone Formation

References

Part III: Structure and Biomechanics

Chapter 21: Skeletal Development: Mechanical Consequences of Growth, Aging, and Disease

I. Developmental Mechanics in Skeletogenesis

II. Mechanical Regulation of Bone Biology

III. Mechanobiologic Self-Design of Bones

IV. Adaptational Mechanics in Aging and Disease

References

Chapter 22: Inhibition of Osteoporosis by Biophysical Intervention

I. Introduction

II. Bone’s Sensitivity to Mechanical Signals

III. Structural Demands on the Skeleton

IV. Regulation of Bone Morphology by Biophysical Stimuli

V. Osteogenic Potential of Low-Magnitude, High-Frequency Signals

VI. Regulating the Bone Cell Response Mechanical Signals

VII. Biophysical Stimuli in the Clinic

VIII. Summary

Acknowledgments

References

Chapter 23: Biomechanics of Age-Related Fractures

I. Introduction

II. Biomechanics of Bone: Basic Concepts and Age-Related Changes

III. Biomechanics of Hip Fractures

IV. Biomechanics of Vertebral Fractures

V. Summary and Clinical Implications

References

Chapter 24: Bone Quality

I. Introduction

II. Chapter Objective

III. The Brooklyn Bridge: A Paradigm for Understanding Bone Quality

IV. Factors Impacting Bone Quality

V. Conclusions

Acknowledgements

References

Part IV: Epidemiology and Risk Factors

Chapter 25: Epidemiologic Methods in of Osteoporosis

I. Introduction

II. Descriptive and Analytic Studies

III. Study Designs

IV. Some Useful Epidemiologic Concepts

V. Some Frequently Used Statistics

VI. Criteria for Deciding Whether an Association is Causal

VII. Sample Size Considerations

VIII. Measurement Error

IX. Conclusions

Acknowledgments

References

Chapter 26: Race, Ethnicity and Osteoporosis

I. Introduction

II. Background and Defi nitions

III. Ethnoepidemiology of Osteoporosis

IV. Ethnic Influences on Risk for Osteoporosis

V. Summary

References

Chapter 27: The Study of Osteoporotic Fractures: Major Findings and Contributions

I. Overview

II. Summary of Key Findings

III. What is a Vertebral Fracture?

IV. Ethnic Differences in Osteoporosis

V. Sleep Disturbance and Risk of Falls and Fractures

VI. Consequences of Fracture: Mortality

VII. Breast Cancer

VIII. Hip Osteoarthritis

IX. SOF Online

X. Summary

SOF Research Group

Acknowledgments

References

Chapter 28: Bone Mineral Acquisition In Utero and during Infancy and Childhood

I. Introduction

II. Quantitative Assessment of Bone Health in Infants and Children

III. Bone Acquisition In Utero

IV. Bone Acquisition in the Preterm Infant

V. Bone Acquisition in Term Infants and Children

References

Chapter 29: Bone Acquisition in Adolescence

I. Introduction

II. Bone Development

III. Mechanical Factors

IV. Nonmechanical Factors

V. Summary

References

Chapter 30: Genetic Determinants of Osteoporosis

I. Introduction

II. Finding Risk Gene Variants for Complex Traits

III. Osteoporosis Risk Gene Variants

IV. Applications and Prospects

References

Chapter 31: Nutrition and Risk for Osteoporosis

I. Introduction

II. Problems in the Investigation of Nutritional Effects on Bone

III. The Notion of a Nutrient Requirement

IV. The Natural Intake of Calcium and Vitamin D

V. Calcium

VI. Vitamin D

VII. Protein

VIII. Vitamin K

IX. Other Essential Nutrients

X. Conclusion

References

Chapter 32: Physical Activity in Prevention of Osteoporosis and Associated Fractures

I. Introduction

II. Bone Adaptation to Physical Loading

III. Physical Activity and Bone

IV. Prevention of Falls and Fall-Related Fractures by Physical Activity

V. Conclusions and Recommendations

References

Chapter 33: Premenopausal Reproductive and Hormonal Characteristics and the Risk for Osteoporosis

I. Introduction

II. Pregnancy

III. Age at First Pregnancy

IV. Parity and Nulliparity

V. Lactation

VI. Ovarian Activity or Menstrual Cycle Characteristics and Bone Mass

VII. Dysfunctional Ovulation

VIII. Oral Contraceptive Use

IX. Progestin-Injectable Contraceptives

X. Oophorectomy

XI. Summary and Implications

References

Chapter 34: Nonskeletal Risk Factors for Osteoporosis and Fractures

I. Physical Characteristics

II. Anthropometric Variables

III. Lifestyle Factors

References

Chapter 35: Falls as Risk Factors for Fracture

I. Introduction

II. Risk Factors for Falls

III. Risk Factors for Injurious Falls

IV. Falls Prevention Strategies

V. Summary and Implications

References

Chapter 36: Assessment of Fracture Risk

I. Introduction

II. Definition of Osteoporotic Fracture

III. Epidemiology of Osteoporotic Fracture

IV. Synthesis of Risk Factors and Risk Assessment Models

V. Summary and Future Directions

References

Chapter 37: Outcomes of Osteoporotic Fractures

I. Introduction

II. Definitions of Functional Outcomes Related to Fracture

III. Osteoporosis-Relevant Quality of Life Assessments

IV. Outcomes of Wrist Fractures

V. Outcomes of Vertebral Fractures

VI. Outcomes of Hip Fractures

VII. Conclusions

References

Part V: Pathophysiology

Chapter 38: Local and Systemic Factors in the Pathogenesis of Osteoporosis

I. Introduction

II. Role of Systemic Hormones

III. Local Factors

IV. Cytokines

V. Prostaglandins

VI. Growth Factors

VII. Colony-Stimulating Factors

VIII. Further Considerations of Interactions of Systemic Hormones and Local Mediators

IX. Conclusions

References

Chapter 39: Animal Models for Osteoporosis

I. Introduction

II. Goals of Animal Models for Osteoporosis

III. Specifi c Animal Models

IV. Evaluation of the Osteopenic Skeleton Animal Models

V. Fracture Repair

VI. Summary

References

Chapter 40: Estrogen, Bone Homeostasis, and Osteoporosis

I. Introduction

II. Secretion and Metabolism of Sex Steroids

III. Direct Effects of Sex Steroids on Bone

IV. Indirect Effects of Sex Steroids on Bone

V. Age- and Sex-Specific Skeletal Changes

VI. Hormonal Determinants of Skeletal Growth and Maturation

VII. Hormonal Determinants of Age-Related Bone Loss in Women

VIII. Hormonal Determinants of Age-Related Bone Loss in Men

IX. The Conundrum of Trabecular Bone Loss in Hormone-Sufficient Young Adults

X. Estrogen Deficiency and Age-Related Osteoporosis

XI. Other Factors Contributing to Osteoporosis

XII. Summary and Conclusions

References

Chapter 41: Postmenopausal Osteoporosis: How the Hormonal Changes of Menopause Cause Bone Loss

I. Steroid Biosynthesis and Menopause

II. Mechanism of Action of Estrogen in Bone

III. Mechanisms of Estrogen Regulation of T Cell TNF Production

IV. T Cell Thymic Output and Bone Loss

V. From Animal Models to Human Disease

VI. Conclusions

References

Chapter 42: Osteoporosis in Men: Epidemiology, Pathophysiology, and Clinical Characterization

I. Fractures in Men

II. The Major Determinants of Bone Health in Men

III. Osteoporosis

IV. The Evaluation of Osteoporosis in Men

V. Therapy

References

Chapter 43: Osteoporosis in Childhood and Adolescence

I. Introduction

II. Principles of Bone Development

III. Definition and Diagnosis of Osteoporosis in Children and Adolescents

IV. Pathogenesis and Treatment of Specific Disorders

V. Summary and Future Directions

References

Chapter 44: Glucocorticoid-Induced Osteporosis

I. Introduction

II. Epidemiology of Glucocorticoid-Induced Osteoporosis

III. The Pathogenesis and Molecular Basis of Glucocorticoid Action on Bone Metabolism and Development

IV. Other Musculoskeletal Effects of Glucocorticoids

V. Treatment Options and Fracture Risk Reduction

VI. Management of Glucocorticoid-Induced Osteoporosis in Children

References

Chapter 45: Adult Scoliosis, Degenerative Disease, and BMD: A Subsegmental Analytic Approach

I. Introduction

II. The Biomechanics of Scoliosis

III. The Use of Dual-Energy X-Ray Absorptiometry to Characterize Physiological Changes in the Spine

IV. Postmenopausal Scoliosis Measured by Subsegmental Analysis

V. Conclusions

Appendix

References

Chapter 46: Mechanisms of Immobilization-Induced Bone Loss

I. Transduction of Mechanical Loading

II. Sensing Strain, Fluid Shear Stress, and Compression

III. Bone Responsiveness to Loss of Weight Bearing

IV. Animal and in Vitro Models

References

Chapter 47: Leptin-Dependent Regulation of Bone Mass

I. Introduction

II. Regulation of Bone Formation by Leptin

III. Regulation of Bone Resorption by Leptin

IV. Summary and Perspectives

References

Chapter 48: Thyroid Hormone and the Skeleton

I. Introduction

II. Thyroid Hormone and Skeletal Growth and Maturation

III. Thyroid Hormone and Mineral Metabolism

IV. Thyroid Hormone and Skeletal Metabolism

V. Bone Mass and Fracture Risk in Thyroid Disease

VI. Prevention of Thyroid Hormone-Induced Bone Loss

References

Chapter 49: Osteoporosis in Gastrointestinal, Pancreatic, and Hepatic Diseases

I. Physiologic Considerations

II. Gastrointestinal Diseases

III. Hepatic Diseases

IV. Bone Disease Complicating Therapy

References

Chapter 50: The Skeletal Actions of Parathyroid Hormone in Primary Hyperparathyroidism and in Osteoporosis

I. Introduction

II. Parathyroid Hormone, Primary Hyperparathyroidism, and the Skeleton

III. Parathyroid Hormone and Osteoporosis

IV. Summary

Acknowledgment

References

Chapter 51: Osteogenesis Imperfecta and Other Defects of Bone Development as Occasional Causes of Adult Osteoporosis

I. Scope of the Problem

II. Osteogenesis imperfecta as a Cause of Adult Osteoporosis

III. Histology of Bone and Bone Histomorphometry in Osteogenesis Imperfecta

IV. Osteoporosis in the Heritable Disorders of Connective Tissue

V. Osteoporosis in Inherited Hematologic Disorders

VI. Osteoporosis in Inherited Hepatic Disease

References

Chapter 52: Osteoporosis Associated with Illnesses and Medications

I. Introduction

II. Metabolic Disorders

III. Medications

References

Chapter 53: Transplantation Osteoporosis

I. Immunosuppression and Osteoporosis

II. Immunosuppressive Agents and Utilization of Preclinical Studies Describing Mechanisms of Action

III. Clinical Studies Supporting the Role of Calcineurin Inhibitors in Bone Loss after Transplantation

IV. Other Immune-Modifying Drugs

V. Summary of Immunosuppressant Agents

VI. Clinical Impact of Transplantation on Bone

VII. Evaluation of Candidates for Transplantation

VIII. Management of Transplantation Osteoporosis

IX. Newer Therapeutic Options

References

Chapter 54: Osteoporosis Associated with Cancer Therapy

I. Introduction

II. Breast Cancer

III. Prostate Cancer

IV. Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

V. Hematopoietic Stem Cell Transplantation and Bone Loss

VI. Skeletal Complications of Radiation Therapy

VII. Childhood Cancer

VIII. Thyroid Cancer

IX. Osteonecrosis of the Jaw

X. Conclusion

References

Chapter 55: Osteoporosis Associated with Pregnancy

I. Introduction

II. Calcium Homeostasis

III. Osteoporosis Associated with Pregnancy

IV. Osteoporosis Associated with Heparin Therapy during Pregnancy

V. Osteoporosis Associated with Magnesium Sulfate Therapy during Pregnancy

VI. Paradoxical Bone Mineralization in Twin-to-Twin Transfusion Syndrome

Acknowledgment

References

Chapter 56: Osteoporosis Associated with Rheumatologic Disorders

I. Introduction

II. Rheumatoid Arthritis

III. Juvenile Rheumatoid Arthritis

IV. Seronegative Spondyloarthropathies

V. Systemic Lupus Erythematosus

Acknowledgments

References

Chapter 57: Oral Bone Loss and Systemic Osteopenia: Potential Treatment and Risks

I. Introduction

II. Diagnosis

III. Risk Factors for Intraoral Bone Loss

IV. Patterns of Progression of Oral Bone Loss

V. Oral Bone Loss and Systemic Osteopenia: Are They Related?

VI. Treatment

VII. Summary

References

Chapter 58: Localized Osteoporosis

I. Introduction

II. Mechanical Stress and Normal Bone Architecture

III. Localized Osteoporosis: Generalizations

IV. Localized Osteoporosis and Fracture

V. Internal Fixation Devices

VI. Inflammatory Disease-Associated Localized Osteoporosis

VII. Reflex Sympathetic Dystrophy

VIII. Transient Osteoporosis of the Hip

IX. Total Hip Replacement

X. Prosthetic Design

XI. Immobilization Osteoporosis: Animal Studies of Localized Bone Loss

XII. Aging

XIII. Hormones and Drugs

XIV. Local Cellular Mechanisms

XV. Summary

References

Part VI: Evaluation and Management

Chapter 59: Evaluation of the Patient with Osteoporosis or at Risk for Osteoporosis

I. Introduction

II. The Decision to Measure

III. What BMD to Measure?

IV. The Evaluation of the Patient with Low BMD

V. Summary and Conclusions

References

Chapter 60: Who Should Be Screened: Who Should Be Treated?

I. Introduction

II. Who Should Be Treated?

III. Who to Test?

IV. Summary

References

Chapter 61: Radiology of Osteoporosis

I. Principal Radiographic Findings in Osteopenia and Osteoporosis

II. Diseases Characterized by Generalized Osteopenia

III. Regional Osteoporosis

References

Chapter 62: Clinical Use of Bone Densitometry

I. Densitometry Techniques

II. Basic Principles of Densitometry

III. Performing Densitometry Measurements with DXA

IV. Monitoring the DXA Scanner

V. Uses of Bone Densitometry

VI. Conclusions

References

Chapter 63: Biochemical Markers of Bone Turnover in Osteoporosis

I. Biochemical Markers of Bone Formation

II. Biochemical Markers of Bone Resorption

III. Clinical Use of Bone Turnover Markers in Postmenopausal Osteoporosis

IV. Bone Turnover Markers in Men

V. Conclusion: what we know and what we need to know

References

Chapter 64: The Conundrum of Compliance and Persistence with Oral Bisphosphonates for Postmenopausal Osteoporosis

I. Introduction

II. Compliance and Persistence with Prescription Medications for Chronic Diseases

III. Osteoporosis

IV. Problems with Research in Compliance and Persistence

V. Improving Compliance and Persistence with Bisphosphonate Therapies

VI. Conclusion

Acknowledgment

References

Chapter 65: An Orthopedic Perspective of Osteoporosis

I. Introduction

II. Biomechanics

III. Specific Injuries

IV. Prevention of Fracture

References

Chapter 66: Lessons from Bone Histomorphometry on the Mechanism of Action of Osteoporosis Drugs

I. Introduction

II. Anticatabolic Therapies

III. Anabolic Therapies

References

Part VII: Pharmacology and Therapeutics

Chapter 67: Design Considerations for Clinical Investigations of Osteoporosis

I. Background: Inference from Phenomena Subject to Variation

II. Types of Investigational Designs

III. Principal Types of Bias with Various Designs

IV. When Controlled Trials and Observational Studies Disagree

V. Design Alternatives

VI. Design Issues of Special Relevance to Investigation of Bone

VII. Ethics of the Placebo

VIII. Burden of Proof and the Null Hypothesis

References

Chapter 68: Regulatory Considerations for the Design and Conduct of Osteoporosis Registration Trials

I. Introduction

II. History of Osteoporosis Guidances

III. FDA and EMEA Guidance Documents

IV. New and Future Initiatives

V. Conclusion

References

Chapter 69: Evidence-Based Osteoporosis Care

I. Introduction

II. Hierarchy of Evidence

III. Critical Appraisal of the Literature

IV. Interpreting and Translating the Evidence into Practice

V. Summary

References

Chapter 70: The Role of Calcium in the Treatment of Osteoporosis

I. Introduction

II. Intestinal Calcium Absorption

III. Calcium and Bone Growth

IV. Calcium and Bone Remodeling

V. Calcium and Fracture Risk

References

Chapter 71: Vitamin D and its Metabolites and Analogs in the Management of Osteoporosis

I. Introduction

II. Vitamin D in the Pathogenesis of Osteoporosis

III. Animal Models

IV. Postmenopausal Osteoporosis

V. Other Osteoporoses

VI. Conclusions

References

Chapter 72: Estrogen Therapy: Prevention and Treatment of Osteoporosis

I. Introduction and Historical Perspective

II. Endogenous Estrogen

III. Trends in Estrogen use

IV. Observational Studies on Fracture Prevention

V. Effects of Hormonal Therapy on Bone Mineral Density and Markers of Bone Remodeling

VI. Randomized Clinical Trials of Hormone Therapy with Fracture Outcomes

VII. Effects of Hormone Therapy on Other Disease Outcomes

VIII. Dose, Regimen, and Type of Estrogen

IX. Discontinuation and Extinction of the Effect of Hormone Therapy

X. Estrogen with Calcium

XI. Summary

XII. Conclusion

References

Chapter 73: Estrogen Analogues: Selective Estrogen Receptor Modulators Phytoestrogens

I. Introduction

II. Classifi cation and Chemical Structure of SERMS and Phytoestrogens

III. Cellular Mechanism of Action of SERMS and Phytoestrogens

IV. Animal Data

V. Clinical Application of SERMS and Phytoestrogens

References

Chapter 74: Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis

I. Introduction and History

II. Pharmacokinetics and Pharmacodynamics

III. Treatment of Postmenopausal Osteoporosis: Efficacy

IV. Other Forms of Osteoporosis

V. Bisphosphonate Safety

VI. Conclusions

References

Chapter 75: Calcitonin in Osteoporosis

I. Introduction

II. Clinical Efficacy in Postmenopausal Osteoporosis

III. Clinical Efficacy in Other Forms of Osteoporosis

IV. Clinical Pharmacology

V. Therapeutic Regimens and Safety

VI. Analgesic Effect

VII. Therapeutic Indications

Acknowledgments

References

Chapter 76: Strontium Ranelate

I. The Need for New Therapies for Fracture Prevention

II. Strontium Ranelate

III. Strontium Ranelate and Vertebral Fracture Risk Reduction

IV. Strontium Ranelate and Hip and Other Non-Vertebral Fracture Risk Reduction

V. Strontium Ranelate in Women over 80 Years of Age

VI. Cost-Effectiveness of Strontium Ranelate Tgerapy

VII. Mechanisms of Action

VIII. Strontium Ranelate and the Cellular Machinery of Bone Modeling and Remodeling

IX. Bone Formation and Resorption In Vitro and In Vitro

X. Conclusion

Acknowledgment

References

Chapter 77: Androgens

I. Introduction

II. Androgens

III. Effects of Testosterone on Bone in Men

IV. Effects of Testosterone on Bone in Women

References

Chapter 78: Treatment with PTH Peptides

I. Introduction

II. Candidates for Anabolic Therapy

III. Postmenopausal Osteoporosis

IV. PTH treatment of Men

V. PTH in Special Populations

VI. Persistence of Effect

VII. Rechallenge with PTH

VIII. Pharmacokinetics of PTH Administration

IX. Mode of Action

X. PTH Peptides Under Development

XI. Conclusion

References

Chapter 79: Growth Hormone and Insulin-Like Growth Factors: Potential Applications and Limitations in the Management of Osteoporosis

I. Introduction

II. Physiology of Growth Hormone-Releasing Hormone (GHRH)—GH-IGF-I

III. The Role of GH/IGF-I in Skeletal Physiology

IV. Pathophysiology of Osteoporosis: Role of GH/IGFS

V. Growth Hormone Therapy for Osteoporosis

VI. IGF-I for the Treatment of Osteoporosis

VII. Summary

Acknowledgments

References

Chapter 80: New Approaches to Osteoporosis Therapeutics

I. Introduction

II. Bone Resorption Inhibitors

III. Anabolic Agents

IV. Summary

References

Index