Osteoporosis

Osteoporosis

4th Edition - June 13, 2013
  • Editors: Robert Marcus, David Dempster, Jane Cauley, David Feldman
  • eBook ISBN: 9780123982520

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Description

Now in its fourth edition, Osteoporosis is a classic reference on this disease, comprising a tremendous wealth of knowledge in a single source not found elsewhere. Written by renowned experts in the field, this two-volume work is a must-have for academic and medical libraries, physicians, researchers, and any company involved in osteoporosis research and development. This newest edition covers everything from basic anatomy and physiology to diagnosis, management and treatment in which direct care costs for osteoporotic fractures in the United States reach up to $18 billion each year. Worldwide, 200 million women ages 60 to 80 suffer from osteoporosis and have a lifetime risk of fracture between 30% and 40%, continuing to make osteoporosis a critical challenge in medicine.

Key Features

  • Recognizes the critical importance of the Wnt signaling pathway for bone health
  • Incorporates new chapters on osteocytes, phosphatonins, mouse genetics, and CNS and bone
  • Examines essential updates on estrogen prevention and treatment and the recent results from the WHO
  • Discusses the controversial topics of screening and clinical trial design for drug registration
  • Includes essential updates on therapeutic uses of calcium, vitamin D, SERMS, bisphosphonates, and parathyroid hormone
  • Offers critical reviews of reproductive and hormonal risk factors, ethnicity, nutrition, therapeutics, management, and economics

Readership

Academic and medical libraries as well as professionals in bone biology, endocrinology, osteology, neuroendocrinology; drug companies developing osteoporosis medications

Table of Contents

  • Preface to the Fourth Edition

    Contributors

    Editor’s Note

    Part I: Introduction

    Chapter 1. The Bone Organ System: Form and Function

    Introduction

    Composition and Organization of Bone

    Cellular Components of Bone

    Bone Homeostasis

    Basic Bone Mechanics

    Summary

    References

    Chapter 2. The Nature of Osteoporosis

    Defining Osteoporosis

    Material and Structural Basis of Skeletal Fragility

    Summary

    References

    Chapter 3. Reflections on Osteoporosis

    Introduction

    Definition

    Diagnosis

    Fragility Fractures

    Bone Density and Fracture Risk

    Pathogenesis

    Prevention

    Treatment

    Summary

    References

    Chapter 4. Reflections on Development of Concepts of Intercellular Communication in Bone

    Introduction

    Calcium Homeostasis – Developments of the 1960s

    Discovery of Calcitonin

    Inhibition of Bone Resorption by Calcitonin

    Lessons from an Osteogenic Sarcoma

    Emergence of Bone Cell Biology

    Could Osteoblasts Regulate Osteoclasts?

    The Origin of Osteoclasts – Mid-1970s

    Osteoblast Regulation of Osteoclasts

    Control of Osteoclast Formation

    Hormone and Cytokine Control of Osteoclast Formation

    The Physiologic Signaling Mechanisms in Osteoclast Control

    Bone Remodeling

    Coupling of Bone Formation to Resorption

    Coupling Factor – from Matrix or Cells?

    Communication from Osteocytes

    Is There a Single “Coupling Factor”, Analogous to RANKL?

    PTHrP as a Local Control Process

    How Might PTHrP Participate?

    Summary

    Acknowledgments

    References

    Chapter 5. Osteo-Odyssey: A Memoir

    Starting Out: From A to B One

    Being the First Postdoc in Larry’s Lab

    In the Academic World: Projects and People

    The Bone World Beyond the Laboratory: ASBMR and NOF

    References

    Part II: Cellular, Molecular, and Developmental Biology of Bone

    Chapter 6. Development of the Skeleton

    Overview

    Patterning the Skeleton

    Endochondral Bone Formation

    Signaling Pathways that Regulate Endochondral Bone Formation

    Intramembranous Bone Formation

    References

    Chapter 7. The Skeletal Stem Cell

    Introduction

    Defining Skeletal Stem Cells

    Migration of Skeletal Stem Cells

    Kinetics of Skeletal Cell Turnover

    Potential Use of Skeletal Stem Cells as Therapy

    Interactions with the Hematopoietic System

    Summary

    References

    Chapter 8. Osteoclast Biology

    Introduction

    Osteoclast Formation

    Osteoclast Function

    Conclusions

    Acknowledgments

    References

    Chapter 9. Osteoblast Biology

    Overview

    Phenotypic Properties of Osteogenic Lineage Cells

    Developmental Sequence of Osteoblast Phenotype Development

    Markers of Osteoblast Maturation Stages

    Genetic and Epigenetic Control of Gene Expression Regulating Skeletal Biology and Pathology

    Concluding Remarks

    Acknowledgments

    References

    Chapter 10. Osteocyte Biology

    Introduction

    Osteocyte Ontogeny

    Osteoid-Osteocytes

    Osteocyte Selective Genes/Proteins and Their Potential Functions

    Morphology of Osteocytes: Lacunocanalicular System and Dendrite Formation

    Osteocyte Cell Models

    Mechanisms and Response of Osteocytes to Mechanical Forces

    Osteocyte Signals for Bone Formation

    Osteocyte Signals for Bone Resorption

    Osteocyte Apoptosis and Autophagy

    Osteocyte Modification of Their Microenvironment

    Osteocyte Regulation of Phosphate Metabolism

    Role of Gap Junctions and Hemichannels in Osteocyte Communication

    Osteocytes in the Embryonic and the Adult Skeleton

    The Implications of Osteocyte Biology for Bone Disease

    Conclusions

    Acknowledgment

    References

    Chapter 11. The Regulatory Role of Matrix Proteins in Mineralization of Bone

    Introduction

    Collagenous Proteins

    Intermediate Cartilage Matrix

    Osteoadherin, Keratocan, and Lumican

    Bone-Enriched Matrix Proteins

    Alkaline Phosphatase

    Osteonectin

    RGD-Containing Glycoproteins

    Osteocalcin

    Matrix Gla Protein

    Periostin

    The Mineralization of Bone Matrix

    Acknowledgments

    References

    Part III: Skeletal Hormones and Regulatory Factors

    Chapter 12. Parathyroid Hormone and Parathyroid Hormone-Related Protein

    Introduction

    Synthesis and Secretion of Parathyroid Hormone

    Metabolism of Parathyroid Hormone

    Bone-Resorbing Action of Parathyroid Hormone

    Effects of PTH on Bone Formation

    Renal Actions of Parathyroid Hormone

    Parathyroid Hormone-Related Protein as a Mediator of Humoral Hypercalcemia of Malignancy

    Physiological Roles of Parathyroid Hormone-Related Protein

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

    Acknowledgments

    References

    Chapter 13. Vitamin D: Biology, Actions, and Clinical Implications

    Introduction

    Vitamin D: Synthesis and Metabolism

    Pathways of Activation and Inactivation of Vitamin D

    Mechanism of 1,25(OH)2D Action

    Nongenomic Actions of Vitamin D

    Genetic Disorders

    1,25(OH)2D3 Analogs

    Action of Vitamin D in Classical Target Organs to Regulate Mineral Homeostasis

    Actions of 1,25(Oh)2D in Nonclassical Target Organs

    Vitamin D and Osteoporosis

    References

    Chapter 14. Regulation of Bone Cell Function by Estrogens

    Introduction

    Estrogen Biosynthesis

    Estrogen Receptors

    Activities in Bone Attributable to Estrogen Receptor α and/or Estrogen Receptor β

    Estrogen Receptor Pharmacology

    Summary

    References

    Chapter 15. Androgens and Skeletal Biology: Basic Mechanisms

    Introduction

    Androgens and the Role of Androgen Metabolism

    Cellular Biology of the Androgen Receptor in the Skeleton

    The Consequences of Androgen Action In Bone Cells

    The Skeletal Effects of Androgen: Animal Studies

    Animal Models of Altered Androgen Responsiveness

    The Role of Androgen Receptors Versus Aromatization of Testosterone

    Androgen Deficiency and Bone Loss: Similarities Between Animal Models and Humans at a Clinical Level

    Summary

    References

    Chapter 16. Phosphatonins

    Introduction

    Phosphorus Homeostasis

    Phosphatonins

    Fibroblast Growth Factor-23

    Secreted Frizzled-Related Protein 4

    Matrix Extracellular Phosphoglycoprotein (MEPE)

    Fibroblast Growth Factor 7

    Summary

    References

    Chapter 17. Skeletal Growth Factors

    Introduction

    Platelet-Derived Growth Factor

    Vascular Endothelial Growth Factor

    Fibroblast Growth Factor

    Transforming Growth Factor Beta

    Bone Morphogenetic Proteins

    Insulin-Like Growth Factor

    Insulin-Like Growth Factor Binding Proteins

    Hepatocyte Growth Factor

    Acknowledgments

    References

    Chapter 18. WNT Signaling in Skeletal Homeostasis and Diseases

    Introduction

    Wnt Signaling

    Wnt Signaling in Skeletal Development, Homeostasis, and Diseases

    Wnt Signaling Interacts with Other Pathways in Bone Mass Regulation

    Wnt Signaling and Mechanical Loading

    Targeting the Wnt Pathway for Therapeutic Intervention

    Summary

    References

    Part IV: Skeletal Structure and Biomechanics

    Chapter 19. The Mechanical Behavior of Bone

    Introduction

    Introduction to Bone Mechanics

    Role of Bone Composition and Microstructure on Bone Mechanical Properties

    Mechanical Behavior of Whole Bone

    Age-Related Changes in Bone Mechanics that Contribute to Fracture

    Summary

    References

    Chapter 20. Cellular and Molecular Mechanotransduction in Bone

    Introduction

    Bone Mechanotransduction

    Forms of Mechanical Stimulation – Tissue Mechanics

    Cellular and Pericellular Mechanics

    Mechanosensing Mechanisms

    Mechanically Activated Intracellular Signaling Pathways

    Cell–cell Pathways that are Activated or Mediate Effects of Mechanical Stimuli

    Conclusion and Implications for Osteoporosis

    References

    Chapter 21. Adaptation of Skeletal Structure to Mechanical Loading

    Introduction and Background

    Diaphyseal Compact Bone

    Cancellous Bone

    Toward a More Mechanistic Understanding of Functional Adaptation in Bone

    Conclusion

    References

    Chapter 22. Biomechanics of Hip and Vertebral Fractures

    Introduction

    Biomechanics of Hip Fractures

    Biomechanics of Vertebral Fractures

    Summary and Clinical Implications

    References

    Chapter 23. Prevention of Osteoporosis by Physical Signals: Defining a Potential Role for Nondrug Strategies in the Treatment of Musculoskeletal Injury and Disease

    Introduction

    Bone’s Sensitivity to Mechanical Signals

    Structural Demands on the Skeleton

    Regulation of Bone Morphology by Physical Signals

    Anabolic Potential of Low-magnitude Mechanical Signals

    Regulating the Bone Cell Response to Mechanical Signals

    Translating Mechanobiology to the Clinic

    Summary

    Acknowledgments

    References

    Part V: Epidemiology of Osteoporosis

    Chapter 24. Epidemiologic Methods in Studies of Osteoporosis

    Introduction

    Descriptive and Analytic Studies

    Study Designs in Analytical Epidemiologic Studies

    Some Useful Epidemiologic Concepts

    Frequently Used Statistics

    Criteria for Deciding whether an Association Matters

    Sample Size Considerations

    Measurement Error

    Discrepant Results Between Studies Examining Similar Research Questions

    Summary

    Acknowledgments

    References

    Chapter 25. Genetic Determinants of Osteoporosis

    Introduction

    Finding Risk Gene Variants for Complex Traits

    Identifying Osteoporosis Risk Gene Variants

    Applications and Prospects

    References

    Chapter 26. Race, Ethnicity, and Osteoporosis

    Introduction

    Background and Definitions

    Ethnoepidemiology of Osteoporosis

    Summary

    References

    Chapter 27. Geographic Variability in Hip and Vertebral Fractures

    Introduction

    Hip Fractures

    Vertebral Fractures

    Conclusion

    Acknowledgements

    References

    Chapter 28. Nutrition and Risk for Osteoporosis

    Introduction

    Problems in the Investigation of Nutritional Effects on Bone

    The Notion of A Nutrient Requirement

    The Natural Intake of Calcium and Vitamin D

    Calcium

    Vitamin D

    Protein

    Vitamin K

    Other Essential Nutrients

    Conclusion

    References

    Chapter 29. Physical Activity and Exercise in the Maintenance of the Adult Skeleton and the Prevention of Osteoporotic Fractures

    Introduction

    The Adult Skeleton and Aging

    Theoretical Basis for Physical Activity and Exercise

    Physical Activity/Exercise Modes

    Exercise and Pharmacological Agents

    Exercise and Fracture Rates

    Exercise Prescription Recommendations

    Conclusions

    References

    Chapter 30. Premenopausal Reproductive and Hormonal Characteristics and the Risk for Osteoporosis

    Introduction

    Pregnancy

    Age at First Pregnancy

    Parity and Nulliparity

    Lactation

    Ovarian Activity or Menstrual Cycle Characteristics and Bone Mass

    Dysfunctional Ovulation

    Oral Contraceptive Use

    Progestin-Injectable Contraceptives

    Oophorectomy

    Summary and Implications

    References

    Chapter 31. Clinical and Epidemiological Studies: Skeletal Changes across Menopause

    Introduction

    Methodological Issues in Studying Menopause

    Pathophysiology of Skeletal Changes at Menopause

    Changes in Bone Density across Menopause

    Bone Structure/Size Changes

    Bone Turnover

    Mechanisms Underlying Bone Loss at Menopause

    Fracture Risk

    Summary

    References

    Chapter 32. Osteoporosis in Men: Epidemiology, Pathophysiology, and Clinical Characterization

    Fractures in Men

    The Incidence of Fractures

    The Determinants of Fracture

    The Major Determinants of Skeletal Health in Men

    Age-Related Bone Loss

    Causes of Age-Related Bone Loss

    Osteoporosis

    The Evaluation of Osteoporosis in Men

    Acknowledgements

    References

    Chapter 33. Falls as Risk Factors for Fracture

    Introduction

    Risk Factors for Falls

    Risk Factors for Injurious Falls

    Falls Prevention Strategies

    Methodologic Approaches to Analyzing Falls

    Summary and Implications

    References

    Chapter 34. Nonskeletal Risk Factors for Osteoporosis and Fractures

    Introduction

    Physical Characteristics

    Anthropometric Variables

    Lifestyle Factors

    References

    Chapter 35. Outcomes Following Osteoporotic Fractures

    Introduction

    Definition

    Risk of Refracture

    Risk of Mortality

    Fracture Burden

    Conclusion

    References

    Part VI: General Pathophysiology of Osteoporosis

    Chapter 36. Skeletal Heterogeneity and the Purposes of Bone Remodeling: Implications for the Understanding of Osteoporosis

    Introduction

    Skeletal Heterogeneity

    The Purposes of Bone Remodeling

    Implications for Understanding Osteoporosis

    References

    Chapter 37. On the Evolution and Contemporary Roles of Bone Remodeling

    Introduction

    The Basics of Bone Remodeling

    Skeletal Involvement in Managing Metabolic Imperatives: Roles and Consequences

    Calcium, Remodeling, and Skeletal Structure

    An Evolutionary Theory on the Origin of Continuous Bone Remodeling

    Bone Remodeling and Reproduction

    Lactational and Postmenopausal Bone Loss as Antagonistic Pleiotropies

    Bone Remodeling, Skeletal Microcracks, and Fatigue Damage

    Effects of Remodeling Inhibition on Bone Strength

    The Partnership of Bone Remodeling and Modeling

    Summary

    References

    Chapter 38. Cytokines and the Pathogenesis of Osteoporosis

    Introduction

    Receptor Activator of Nuclear Factor-Kappab Ligand (RANKL), Receptor Activator of Nuclear Factor-Kappab (RANK) and Osteoprotegerin (OPG)

    Macrophage Colony-Stimulating Factor

    Additional Colony Stimulating Factors

    Interleukin-1

    Tumor Necrosis Factor

    Additional Tumor Necrosis Factor Superfamily Members

    Interleukin-6

    Additional Interleukin-6 Family Members

    Interleukin-8 and Other Chemokines

    Interleukin-10

    Interleukin 12

    Interleukin 15

    Interleukin 17, Interleukin 23, and Interleukin 27

    Interleukin 18

    Interferons

    Additional Cytokines

    References

    Chapter 39. Animal Models for Osteoporosis

    Introduction

    Goals of Animal Models for Osteoporosis

    Specific Animal Models

    Mouse

    Evaluation of the Osteopenic Skeleton in Animal Models

    Fracture Repair

    Summary

    References

    Chapter 40. Bone and Fat

    Introduction

    Bone and Fat—Epidemiological Studies

    Physiology of Adipose Tissue and Energy Expenditure

    Adipocytic and Osteoblastic Differentiation

    Hormonal Factors that Regulate Bone and Energy Metabolism

    Drug-induced Changes in Bone and Fat

    References

    Chapter 41. Bone Mineral Acquisition in Utero and During Infancy and Childhood

    Introduction

    Quantitative Assessment of Bone Health in Infants and Children

    Bone Acquisition in Utero

    Bone Acquisition in the Preterm Infant

    Bone Acquisition in Term Infants and Children

    References

    Chapter 42. Bone Acquisition in Adolescence

    Introduction

    Measuring Bone Acquisition

    Overview of Bone Accrual During Adolescence

    Determinants of Bone Acquisition During Adolescence

    Summary and Future Directions

    References

    Chapter 43. Osteoporosis in Childhood and Adolescence

    Introduction

    Principles of Bone Development

    Definition and Diagnosis of Osteoporosis in Children and Adolescents

    Pathogenesis and Treatment of Specific Disorders

    Summary and Future Directions

    References

    Chapter 44. Osteoporosis Associated with Pregnancy

    Introduction

    Calcium Homeostasis

    Osteoporosis Associated With Pregnancy

    Osteoporosis Associated with Heparin Therapy During Pregnancy

    Osteoporosis Associated with Magnesium Sulfate Therapy During Pregnancy

    Paradoxical Bone Mineralization in Twin-To-Twin Transfusion Syndrome

    Acknowledgments

    References

    Chapter 45. Osteoporosis in Premenopausal Women

    Introduction

    Diagnosis of Osteoporosis in Premenopausal Women

    Secondary Causes of Osteoporosis in Premenopausal Women

    Treatment Considerations for Premenopausal Women with Low Trauma Fractures And/Or Low BMD

    Summary and Conclusions

    References

    Chapter 46. Estrogen Deficiency, Postmenopausal Osteoporosis, and Age-Related Bone Loss

    Introduction

    Age- and Sex-Specific Skeletal Changes

    Secretion and Metabolism of Sex Steroids

    Direct Effects of Sex Steroids on Bone

    Indirect Effects of Sex Steroids On Bone

    Hormonal Determinants of Skeletal Growth And Maturation

    Hormonal Determinants of Age-Related Bone Loss in Women

    Hormonal Determinants of Age-Related Bone Loss in Men

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

    Other Factors Contributing to Osteoporosis

    References

    Part VII: Spectrum of Secondary Osteoporosis

    Chapter 47. Immobilization Osteoporosis

    Introduction

    Animal Studies

    Cellular and Molecular Mechanisms of Reduced Bone Formation after Unloading

    Human Studies

    References

    Chapter 48. Osteoporosis Associated with Illnesses and Medications

    Introduction

    Metabolic Disorders

    Medications

    References

    Chapter 49. Glucocorticoid-Induced Osteoporosis

    Introduction

    Epidemiology of Glucocorticoid-Induced Osteoporosis

    Prevention and Treatment

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

    Other Musculoskeletal Effects of Glucocorticoids

    Treatment Options and Fracture Risk Reduction

    Management of Glucocorticoid-Induced Osteoporosis in Children

    References

    Chapter 50. Anticonvulsant-Related Bone Disease

    Introduction and Historical Perspective

    Epidemiology

    Clinical Manifestations

    Specific Antiepileptic Drugs

    Mechanisms of Action

    Treatment

    References

    Chapter 51. Thyroid Hormone and the Skeleton

    Introduction

    Thyroid Hormone and Skeletal Growth and Maturation

    Thyroid Hormone and Mineral Metabolism

    Thyroid Hormone and Skeletal Metabolism

    Bone Mass and Fracture Risk in Thyroid Disease

    Prevention of Thyroid Hormone-Induced Bone Loss

    References

    Chapter 52. The Skeletal Actions of Parathyroid Hormone in Primary Hyperparathyroidism and in Osteoporosis

    Introduction

    Parathyroid Hormone, Primary Hyperparathyroidism, and the Skeleton

    Parathyroid Hormone And Osteoporosis

    Summary

    Acknowledgment

    References

    Chapter 53. Osteogenesis Imperfecta and Other Defects of Bone Development as Occasional Causes of Adult Osteoporosis

    Scope of the Problem

    Osteogenesis Imperfecta as a Cause of Adult Osteoporosis

    Type I Collagen and Osteogenesis Imperfecta

    Clinical Overview of Osteogenesis Imperfecta

    Type IV Osteogenesis Imperfecta (Omim 166,220)

    Recessive forms of Osteogenesis Imperfecta

    Genotype Expression in Osteogenesis Imperfecta

    The Pathophysiology of Osteogenesis Imperfecta

    Organ Involvement in Osteogenesis Imperfecta

    Osteoporosis in the Heritable Disorders of Connective Tissue

    References

    Chapter 54. HIV and Osteoporosis

    Aging and HIV

    Etiology of Low Bone Mineral Density in HIV

    Other Contributing Factors

    Vitamin D Deficiency

    Special Populations

    Nonskeletal Risk Factors for Fracture

    Treatment Considerations

    Summary

    Reference

    Chapter 55. Obesity, Diabetes, and Fractures

    Obesity and Fractures

    Diabetes Mellitus, Bone Mass, and Fractures

    Conclusions

    References

    Chapter 56. Osteoporosis in Organ Transplant Patients

    Skeletal Effects of Immunosuppressive Drugs

    Effects of Vitamin D on Immunity and Graft Rejection

    Effect of Transplantation on Bone and Mineral Metabolism

    Evaluation and Management of Osteoporosis in Patients Awaiting Transplantation

    Prevention and Treatment of Transplantation Osteoporosis

    Summary and Conclusions

    References

    Chapter 57. Osteoporosis Associated with Rheumatologic Disorders

    Introduction

    Rheumatoid Arthritis

    Juvenile Idiopathic Arthritis

    Seronegative Spondyloarthropathies

    Systemic Lupus Erythematosus

    Acknowledgments

    References

    Chapter 58. Osteoporosis Associated with Chronic Kidney Disease

    Introduction

    Stages Of Chronic Kidney Disease

    Epidemiology

    Pathophysiology

    Skeletal Manifestations Of Chronic Kidney Disease

    Extraskeletal Calcifications

    Treatment

    Hypercalciuria

    References

    Chapter 59. Oral Bone Loss and Systemic Osteoporosis: Weighing the Risk Benefit Ratio of Treatment

    Introduction

    Diagnosis

    Risk Factors for Intraoral Bone Loss

    Patterns of Progression of Oral Bone Loss

    Oral Bone Loss and Systemic Osteopenia: are They Related?

    Treatment of Oral and Systemic Bone Loss

    Bisphosphonates: Risk or Benefit?

    References

    Part VIII: Cancer and Osteoporosis

    Chapter 60. Cancer Treatment-Induced Bone Loss in Patients with Breast Cancer: Pathophysiology and Clinical Perspectives

    Introduction

    Identifying Fracture Risk in Women With Breast Cancer

    Bone Loss in Premenopausal Women Receiving Cancer Treatments

    Maintaining Bone Health in Breast Cancer Patients

    Disease Modifying Effects of Bone Targeted Treatments

    Safety

    Conclusions

    Acknowledgments

    References

    Chapter 61. Pathophysiology—Prostate Cancer

    Introduction

    Normal Bone Physiology

    Osteoporosis and Androgen Deprivation Therapy Among Men

    Distinction Between Osteoporotic Fractures and Disease-related Fractures

    Therapy: Classes of Agents

    Clinical Trials With BMD and Fracture End Points

    Risk Assessment in Men With Prostate Cancer

    Safety of Available Therapies

    Conclusions and Recommendations

    References

    Chapter 62. Mechanisms of Bone Destruction in Myeloma

    Introduction

    Prevalence and Presentation of Myeloma Bone Disease

    The Clinical and Economic Burden of Myeloma Bone Disease

    Pathophysiology of Myeloma Bone Disease

    Pathogenesis of the Increased Osteoclast Activity in Myeloma

    Osteoblast Suppression in Myeloma

    Treatment of Myeloma Bone Disease

    Conclusions

    References

    Part IX: Diagnosis and Evaluation

    Chapter 63. Evaluation of the Patient at Risk for Osteoporosis

    Introduction

    Medical History

    Physical Exam

    Laboratory Studies

    Imaging

    Invasive Procedures

    Treatment Decisions

    Conclusions

    References

    Chapter 64. Imaging of Osteoporosis

    Introduction

    Principal Radiographic Findings in Osteopenia and Osteoporosis

    Diseases Characterized by Generalized Osteopenia

    Regional Osteoporosis

    References

    Chapter 65. Osteoporosis: Who Should be Treated? Who Should be Screened?

    Introduction

    Who Should be Treated?

    FRAX Risk Calculator

    Potential Impact of Frax Results

    Who Should be Screened for OSTEOPOROSIS—BASED Upon Cost Effectiveness

    How Well are Osteoporosis Treatment and Screening Guidelines Followed?

    Summary

    References

    Chapter 66. Clinical Use of Bone Densitometry

    Introduction

    The Evolution of Bone Densitometry

    Dual Energy X-ray Absorptiometry

    Other Technologies for the Measurement of Bone Density

    The Diagnosis of Osteoporosis Based on the Measurement of Bone Density

    Assessing Fracture Risk With Bone Densitometry

    FRAX®

    DXA-based Vertebral Fracture Assessment

    DXA-based Aortic Calcification Assessment

    Monitoring Changes in Bone Density After Pharmacologic Treatment

    Guidelines for Bone Density Testing

    Summary

    References

    Chapter 67. Biochemical Markers of Bone Turnover in Osteoporosis

    Introduction

    Biochemical Markers of Bone Formation

    Biochemical Markers of Bone Resorption

    Analytical and Preanalytical Variability

    Clinical Use of Bone Turnover Markers in Postmenopausal Osteoporosis

    Bone Turnover Markers in Men

    Bone Turnover MARKERS—CLINICAL Studies Versus Clinical Practice

    Conclusion: What We Know, What We Need to Know

    References

    Chapter 68. Fracture Risk Assessment: The Development and Application of FRAX®

    Introduction

    Development and Construct of FRAX®

    Calibration of FRAX®

    Performance Characteristics

    Reversibility of Risk

    Validation

    Intervention Thresholds

    Interpretation and Limitations of FRAX®

    Risk Factors Not Considered in FRAX®

    Other Applications of FRAX®

    References

    Part X: PATIENT MANAGEMENT

    Chapter 69. Orthopedic Aspects of Osteoporosis

    Orthopedic Aspects of Osteoporosis

    Geriatric Fracture Care and Care Treatment Pathways

    Osteoporotic Bone and Orthopedic Hardware

    Lower Extremity Fractures

    Upper Extremity Fractures

    Spine and Pelvic Fractures

    Osteoporosis and Elective Orthopedic Procedures

    Osteoporosis Care in Orthopedic Patients

    References

    Chapter 70. Falls Prevention Interventions

    Epidemiology of Falls and Fall-related Injuries in Older People

    Risk Factors of Falls

    Fall Risk Screening and Assessment

    Fall Prevention Strategies

    Summary

    References

    Chapter 71. Physical Therapy, Physical Modalities, and Exercise Regimens in the Management of Osteoporosis

    Introduction

    Physical Therapist Practice

    Prevention of Fracture

    Management of the Patient Following A Vertebral Fracture

    Management of the Patient Following A Hip Fracture

    Exercise Prescription and Exercise Programs

    Conclusion

    References

    Chapter 72. Calcium in the Treatment of Osteoporosis

    Introduction

    Cotherapy and Therapy

    Bone Remodeling, Osteoporosis, and Calcium

    The Critical Role of Protein Intake

    Calcium Sources and Amounts

    Conclusion

    Note

    References

    Chapter 73. Vitamin D and its Metabolites and Analogs in the Management of Osteoporosis

    Introduction

    Nomenclature

    Vitamin D in the Pathogenesis of Osteoporosis

    Animal Models

    Postmenopausal Osteoporosis

    Other Forms of Osteoporosis

    Conclusions

    Note

    References

    Chapter 74. Alternative Therapy through Nutrients and Nutraceuticals

    Introduction

    Phytoestrogens

    Dehydroepiandrosterone

    Antioxidants

    Bicarbonates

    B-Vitamins and Homocysteine

    Minerals

    Conclusion

    References

    Part XI: Pharmacotherapeutics

    Chapter 75. Design Considerations for Clinical Investigations of Osteoporosis

    Background: Inference from Phenomena Subject to Variation

    Types of Investigational Designs

    Principal Types of Bias with Various Designs

    When Controlled Trials and Observational Studies Disagree

    Design Alternatives

    Design Issues of Special Relevance to Investigation of Bone

    Ethics of the Placebo

    The Dilemma

    Burden of Proof and the Null Hypothesis

    References

    Chapter 76. Lessons from Bone Histomorphometry on the Mechanisms of Action of Osteoporosis Drugs

    Introduction

    Anticatabolic Therapies

    Anabolic Therapies

    References

    Chapter 77. Estrogen and Estrogen Analogs for Prevention and Treatment of Osteoporosis

    Introduction

    Estrogen—The First Osteoporosis Therapy

    Estrogen Analogs

    Points to Consider

    References

    Chapter 78. Androgens

    Introduction

    Androgens

    Effects of Testosterone on Bone in Men

    Effects of Testosterone on Bone in Women

    References

    Chapter 79. Calcitonin in Osteoporosis

    Introduction

    Clinical Pharmacology

    Clinical Efficacy in Postmenopausal Osteoporosis

    Clinical Efficacy in Other Forms of Osteoporosis

    Therapeutic Regimens

    Analgesic Effect

    Safety

    Acknowledgments

    References

    Chapter 80. Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis

    Introduction and History

    Pharmacokinetics and Pharmacodynamics

    Treatment of Postmenopausal Osteoporosis: Efficacy

    Bisphosphonate Safety

    Bisphosphonate Drug Holidays

    Summary

    References

    Chapter 81. Osteonecrosis of the Jaw and Atypical Femoral Fractures

    Introduction

    Osteonecrosis of the Jaw

    Atypical Femur Fractures

    References

    Chapter 82. Condition Critical: Compliance and Persistence with Osteoporosis Medications

    Introduction

    Terminology for Medication-based Behaviors

    Compliance and Persistence With Osteoporosis Medications: the Problem

    Medication-related Reasons for Noncompliance and Nonpersistence

    Compliance and Persistence With Osteoporosis Medications: a Solution(s)?

    What Went Wrong? Problems With Recent Interventions

    Summary

    References

    Chapter 83. Denosumab for the Treatment of Osteoporosis

    Introduction

    Denosumab

    Efficacy

    Bone Histology and Histomorphometry

    Withdrawal of Therapy

    Safety and Tolerability

    Denosumab in Other Populations

    Summary

    References

    Chapter 84. Strontium Ranelate in the Prevention of Osteoporotic Fractures

    Introduction

    The Antifracture Efficacy of Strontium Ranelate

    The Antifracture Effects of Strontium Ranelate in Specific Populations

    Microstructure

    Quality of Life and COST-effectiveness

    Safety of Strontium Ranelate

    Preclinical Studies With Strontium Ranelate

    Recent Developments

    Conclusion

    Conflicts of Interest Statement

    References

    Chapter 85. Parathyroid Hormone Treatment for Osteoporosis

    Introduction

    Candidates for Anabolic Therapy

    Mode of Action

    Postmenopausal Osteoporosis

    Parathyroid Hormone (1–84) as Monotherapy

    Parathyroid Hormone and Antiresorptive Combination/sequential Therapy

    Parathyroid Hormone and Hormone Therapy

    Parathyroid Hormone Treatment of MEN

    Parathyroid Hormone in Special Populations

    Persistence of Effect

    Rechallenge With Parathyroid Hormone

    Conclusion Regarding Osteoporosis Treatment

    Other Possible Clinical Applications for Parathyroid Hormone Treatment

    References

    Chapter 86. New Approaches to Osteoporosis Therapeutics

    Introduction

    Therapeutic Approaches with Osteoanabolic Therapy

    Denosumab: New Concepts Related to Mechanisms of Action

    Cathepsin K Inhibition

    Newer Developments with Bisphosphonate Therapy

    Therapeutics Based Upon the Wnt Signaling Pathway

    Therapeutics Based Upon Other Signaling Pathways

    Acknowledgements

    References

    Chapter 87. The Past, Present, and Uncertain Future of Therapeutic Innovation in Osteoporosis

    Introduction

    The Past in Osteoporosis Therapeutics: A SHORT TAKE on How We Got Here

    The Limitations of Currently Available Drug Therapies

    Threats to Pharmaceutical Innovation in Osteoporosis Therapy

    The Big Picture: A Sobering Challenge

    Where Do We Go From Here?

    Suggested Information Sources

    References

    Color Plates

    Color Plates

    Index

Product details

  • No. of pages: 2116
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: June 13, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780123982520

About the Editors

Robert Marcus

Robert Marcus
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), Merck’s Fracture Intervention Trial (FIT), Lilly’s Multiple Outcomes of Raloxifene Intervention (MORE), and Lilly’s 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 Lilly’s 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.

Affiliations and Expertise

Professor Emeritus, Department of Medicine, Stanford University School of Medicine, CA, USA

David Dempster

David Dempster
David W. Dempster, PhD, is Professor of Clinical Pathology and Cell Biology at Columbia University in New York. He obtained his PhD from the University of Glasgow in Scotland and completed postdoctoral studies in Switzerland and France. Dr. Dempster is a Past President of the International Society of Bone Morphometry and a member of the Scientific Advisory Council of the National Osteoporosis Foundation. He is also a Fellow of the Royal Microscopical Society. Dr. Dempster’s iconic micrographs of osteoporotic bone have been widely reproduced in the scientific and popular press, including being displayed at the Smithsonian Institution in Washington, DC. Dr. Dempster is an Associate Editor of Osteoporosis International, and serves on the editorial boards of the Journal of Bone and Mineral Research, Bone and the Journal of Clinical Densitometry. His research studies have been continuously supported by the National Institutes of Health for the past 25 years. Dr. Dempster has published over 200 research papers on the pathophysiology and treatment of bone disese.

Affiliations and Expertise

Professor of Clinical Pathology and Cell Biology, Columbia University School of Medicine; Director Emeritus, Regional Bone Center, Helen Hayes Hospital, New York, NY, USA

Jane Cauley

Dr. Cauley, DrPH, is a Distinguished Professor and Executive Vice Chair, Department of Epidemiology, Graduate School of Public Health (GSPH), University of Pittsburgh (Pennsylvania). Her primary research interest is the epidemiology of osteoporosis especially the large worldwide ethnic and geographic variability in fracture, osteoporosis screening and treatment, risk factors for fractures and the consequences of osteoporosis in both men and women. Her research has also focused on women's health and aging, falls, the interaction between endogenous and exogenous hormones, risk factors, and disease outcomes. She was principal investigator for several large cohort studies including the Study of Osteoporotic Fractures (SOF) and the Osteoporotic Fractures in Men (MrOS) study. She is a co-investigator for the Study of Women’s Health Across the Nation (SWAN) with particular emphases on skeletal health and physical function and body composition changes, novel measures of hip strength and the trabecular bone score across menopause. She initiated breast cancer follow-up in SOF and was the first to demonstrate an association between bone mineral density (BMD) and breast cancer, suggesting that BMD could be used as a cumulative measure of lifetime exposure to estrogen. Dr. Cauley has authored more than 800 papers for scientific journals and 28, book chapters. She co-edited a book entitled the Epidemiology of Aging, published in 2012.

Affiliations and Expertise

Distinguished Professor of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, United States

David Feldman

Affiliations and Expertise

Stanford University School of Medicine, Stanford, California, USA

Latest reviews

(Total rating for all reviews)

  • RayShenefelt Sat Dec 21 2019

    comprehensive coverage

    This multi-authored, thick 2 volume book is multi-authored. It is very comprehensive. There is quite a bit of duplication of information among various authors, but this helps to provide perspective.