Dynamics of Bone and Cartilage Metabolism - Principles and Clinical Applications

Dynamics of Bone and Cartilage Metabolism

Dynamics of Bone and Cartilage Metabolism

Contents

Contributors

Preface to the Second Edition

Components of the Organic Extracellular Matrix of Bone and Cartilage

Structure, Biosynthesis and Gene Regulation of Collagens in Cartilage and Bone

I. INTRODUCTION

II. THE COLLAGEN FAMILIES

III. BONE COLLAGENS

IV. CARTILAGE COLLAGENS

V. COLLAGEN BIOSYNTHESIS

VI. COLLAGEN GENES AND TRANSCRIPTIONAL REGULATION

VII. FACTORS REGULATING COLLAGEN BIOSYNTHESIS

VIII. CONCLUSIONS

Fibrillogenesis and Maturation of Collagens

I. INTRODUCTION

II. FIBRILLOGENESIS

III. CROSS-LINKING

IV. CONCLUDING REMARKS

Vitamin K Dependent Proteins of Bone and Cartilage

I. ABSTRACT

II. INTRODUCTION

III. OSTEOCALCIN

IV. MATRIX Gla PROTEIN

V. Gas6

VI. VITAMIN K/WARFARIN

Noncollagenous Proteins; Glycoproteins and Related Proteins

I. INTRODUCTION

II. CARTILAGE EXTRACELLULAR MATRIX

III. BONE, EXTRACELLULAR MATRIX

IV. CONCLUDING REMARKS

Proteoglycans and Glycosaminoglycans

I. INTRODUCTION

II. GLYCOSAMINOGLYCANS

III. PROTEOGLYCANS IN CARTILAGE

IV. AGGRECAN

V. LEUCINE-RICH PROTEOGLYCANS IN CARTILAGE AND BONE

VI. PERLECAN IN CARTILAGE

Growth Factors

I. INTRODUCTION

II. INSULIN-LIKE GROWTH FACTORS

III. THE TRANSFORMING GROWTH FACTOR-BETA/BONE MORPHOGENETIC PROTEIN SUPERFAMILY

IV. FIBROBLAST GROWTH FACTORS

V. Wnts

VI. ADDITIONAL GROWTH FACTORS

VII. SUMMARY

Prostaglandins and Proinflammatory Cytokines

I. INTRODUCTION

II. PROSTAGLANDINS

III. THE ROLE THAT CYTOKINES HAVE IN OSTEOCLAST FORMATION AND FUNCTION

IV. THE ROLE THAT PROINFLAMMATORY CYTOKINES HAVE IN BONE AND CARTILAGE METABOLISM

Integrins and Other Adhesion Molecules

I. ABSTRACT

II. INTRODUCTION

III. MOLECULAR STRUCTURE OF ADHESION MOLECULES

IV. ADHESION MOLECULES IN CELLS OF THE OSTEOBLAST LINEAGE

V. ADHESION MOLECULES IN OSTEOCLASTS

VI. ADHESION MOLECULES IN CHONDROCYTES

VII. CONCLUSION

Alkaline Phosphatases

I. INTRODUCTION

II. STRUCTURE AND REGULATION OF THE TNAP GENE

III. PROTEIN STRUCTURE

IV. FUNCTION OF TNAP

V. CLINICAL USE

Acid Phosphatases

I. ACID PHOSPHATASES

II. TARTRATE-RESISTANT ACID PHOSPHATASE (TRACP)

III. PROSTATIC ACID PHOSPHATASE (PAP)

Matrix Proteinases

I. INTRODUCTION

II. ASPARTIC PROTEINASES

III. CYSTEINE PROTEINASES

IV. SERINE PROTEINASES

V. METALLOPROTEINASES

Structure and Metabolism of the Extracellular Matrix of Bone and Cartilage

Mineralization, Structure and Function of Bone

I. ABSTRACT

II. THE STRUCTURE AND FUNCTION OF BONE

III. BONE MINERALIZATION

IV. BONE MODELING AND REMODELING

Bone Structure and Strength

I. INTRODUCTION

II. GRAVITY AND THE NEED FOR STIFFNESS, FLEXIBILITY, LIGHTNESS AND SPEED

III. THE MATERIAL COMPOSITION AND STRUCTURAL DESIGN OF BONE

IV. BONE MODELING AND REMODELING - THE MECHANISM OF BONE'S CONSTRUCTION DURING GROWTH AND DECAY WITH ADVANCING AGE

V. STRENGTH MAINTENANCE

VI. CONCLUSION

The Cells of Bone

I. ABSTRACT

II. INTRODUCTION

III. DEVELOPMENTAL SIGNALS FOR CARTILAGE AND BONE TISSUE FORMATION

IV. OSTEOGENIC LINEAGE CELLS

V. THE OSTEOCLAST: A FUNCTIONALLY UNIQUE CELL FOR PHYSIOLOGICALLY REGULATED RESORPTION OF BONE MINERAL

VI. PERSPECTIVES

Signaling in Bone

I. ABSTRACT

II. INTRODUCTION

III. THE CONTROL OF OSTEOCLASTS

IV. SIGNALING IN THE CONTROL OF OSTEOCLAST ACTIVITY

V. SIGNALS FROM THE OSTEOBLAST LINEAGE THAT CONTROL OSTEOCLAST FORMATION

VI. HORMONE AND CYTOKINE INFLUENCES ON THE CONTACT DEPENDENT REGULATION OF OSTEOCLASTS

VII. DISCOVERY OF THE PHYSIOLOGICAL SIGNALING MECHANISMS IN OSTEOCLAST CONTROL

VIII. RANK SIGNALING

IX. COUPLING OF BONE FORMATION TO RESORPTION - RELEASE OF GROWTH FACTORS FROM BONE MATRIX

X. COUPLING OF BONE FORMATION TO RESORPTION - AUTOCRINE/PARACRINE REGULATION BY DIFFERENTIATING OSTEOBLASTS

XI. COUPLING OF BONE FORMATION TO RESORPTION - ARE OSTEOCLASTS A SOURCE OF COUPLING ACTIVITY?

Parathyroid Hormone: Structure, Function and Dynamic Actions

I. INTRODUCTION

II. STRUCTURE OF THE PTH GENE

III. CHROMOSOME LOCATION

IV. CONTROL OF GENE EXPRESSION

V. BIOSYNTHESIS OF PARATHYROID HORMONE

VI. METABOLISM OF PARATHYROID HORMONE

VII. RECEPTOR INTERACTIONS OF PARATHYROID HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN

VIII. STRUCTURE OF THE PTH/PTHrP (PTH1R) RECEPTOR

IX. ACTIVATION OF THE CYCLIC ADENOSINE MONOPHOSPHATE SECOND-MESSENGER SYSTEM BY PARATHYROID HORMONE

X. IDENTIFICATION OF A SECOND PTH RECEPTOR

XI. PHYSIOLOGICAL ACTIONS OF PTH

XII. CELL-TO-CELL COMMUNICATION: OSTEOBLASTS AND OSTEOCLASTS

XIII. PREFERENTIAL ACTIONS OF PTH AT SELECTED SKELETAL SITES

Interaction of Parathyroid Hormone- related Peptide with the Skeleton

I. ABSTRACT

II. INTRODUCTION

III. MOLECULAR BIOLOGY AND MECHANISM OF ACTION

IV. THE SKELETAL ACTIONS OF PTHrP

V. SUMMARY

The Vitamin D Hormone and its Nuclear Receptor: Mechanisms Involved in Bone Biology

I. INTRODUCTION

II. METABOLISM OF VITAMIN D

III. NUCLEAR VITAMIN D RECEPTOR

IV. VITAMIN D AND BONE CELLS

V. PATHOLOGY AND THERAPY RELATED TO VITAMIN D AVAILABILITY, METABOLISM, AND FUNCTION

VI. CONCLUSIONS

Sex Steroid Effects on Bone Metabolism

I. ABSTRACT

II. INTRODUCTION

III. MOLECULAR STRUCTURES, SYNTHESIS, MECHANISM OF ACTION OF MAJOR SEX STEROIDS, AND TRANSCRIPTIONAL COREGULATOR FUNCTION

IV. EFFECTS OF SEX STEROIDS ON BONE CELLS AND BONE TURNOVER

V. EFFECTS OF ESTROGENS AND ANDROGENS ON BONE METABOLISM IN MEN VERSUS WOMEN

VI. EFFECTS OF SEX STEROIDS ON EXTRASKELETAL CALCIUM HOMEOSTASIS

VII. SUMMARY

Physiology of Calcium and Phosphate Homeostases

I. ABSTRACT

II. INTRODUCTION

III. BODY DISTRIBUTION OF CALCIUM

IV. DETERMINANTS OF EXTRACELLULAR CALCIUM CONCENTRATION

V. RELATIVE IMPORTANCE OF THE VARIOUS CALCIUM FLUXESIN CONTROLLING EXTRACELLULAR CALCIUM HOMEOSTASIS

VI. HOMEOSTATIC RESPONSES TO HYPOCALCEMIA

VII. CALCIUM AND BONE GROWTH

VIII. BODY DISTRIBUTION OF PHOSPHORUS

IX. DETERMINANTS OF EXTRACELLULAR PHOSPHATE CONCENTRATION

X. HOMEOSTATIC RESPONSES TO CHANGES IN PHOSPHATE SUPPLY OR DEMAND

XI. CONCLUSIONS

The Central Control of Bone Remodeling

I. INTRODUCTION

II. ACTIONS OF LEPTIN

III. SYMPATHETIC NERVOUS SYSTEM

IV. NEUROPEPTIDE Y AND THE Y RECEPTORS

V. INTERACTION BETWEEN LEPTIN AND Y2-REGULATED BONE ANTIOSTEOGENIC PATHWAYS

VI. CONCLUDING REMARKS

New Concepts in Bone Remodeling

I. INTRODUCTION

II. AN OVERVIEW OF THE REMODELING CYCLE

III. FUNCTIONS OF BONE REMODELING

IV. THE ROLE OF APOPTOSIS IN REGULATING BONE BALANCE

V. POSSIBLE MECHANISMS WHEREBY A REDUCTION IN ACTIVATION FREQUENCY MAY PROTECT AGAINST FRACTURE

Products of Bone Collagen Metabolism

I. INTRODUCTION

II. PRODUCTS OF BONE COLLAGEN SYNTHESIS, THE PROCOLLAGEN PROPEPTIDES

III. DEGRADATION PRODUCTS OF TYPE I COLLAGEN

IV. CLOSING REMARKS

Supramolecular Structure of Cartilage Matrix

I. SUMMARY

II. INTRODUCTION

III. LIGHT AND ELECTRON MICROGRAPHY

IV. BIOCHEMISTRY OF CARTILAGE

V. STUDIES OF FIBRIL STRUCTURES BY X-RAY DIFFRACTION

VI. STRUCTURE OF FIBRIL FRAGMENTS OBTAINED BY MECHANICAL DISRUPTION OF TISSUE

VII. STUDIES OF COLLAGEN CROSSLINKING IN CARTILAGE FIBRILS

VIII. RECONSTITUTION OF AGGREGATES FROM SOLUBLE COLLAGENS AND OTHER MACROMOLECULES

IX. STUDIES OF TRANSGENIC MICE AND OF HUMAN GENETIC MATRIX DISEASES

X. CORRELATING STRUCTURE WITH THE BIOMECHANICAL ROLE OF ARTICULAR CARTILAGE

XI. MODELS OF CARTILAGE FIBRIL STRUCTURE

XII. FUTURE PERSPECTIVES

Products of Cartilage Metabolism

I. INTRODUCTION

II. THE CHONDROCYTE AND ITS EXTRACELLULAR MATRIX

III. PRODUCTS OF COLLAGEN METABOLISM

IV. PRODUCTS OF AGGRECAN METABOLISM

V. PRODUCTS OF THE METABOLISM OF OTHER PROTEOGLYCANS

VI. PRODUCTS OF THE METABOLISM OF LINK PROTEIN AND HYALURONAN

VII. OTHER PRODUCTS OF CHONDROCYTE METABOLISM

VIII. CONCLUDING STATEMENT

Fluid Dynamics of the Joint Space and Trafficking of Matrix Products

I. INTRODUCTION

II. INTERPRETATION OF MARKER DATA AND STRATEGIES FOR DEALING WITH THEM

III. CONCLUSION

Transgenic Models of Bone Disease

I. INTRODUCTION

II. GENERATION OF MOUSE MODELS

III. TRANSGENIC MODELS IN BONE BIOLOGY

IV. PERSPECTIVES AND FUTURE DIRECTIONS

Markers of Bone and Cartilage Metabolism

The Role of Genetic Variation in Osteoporosis

I. ABSTRACT

II. OSTEOPOROSIS HAS GENETIC INFLUENCES

III. GENOME-WIDE APPROACHES TO FIND THE GENES

IV. ASSOCIATION ANALYSIS OF CANDIDATE GENE POLYMORPHISMS

V. HAPLOTYPES

VI. META-ANALYSES

VII. OSTEOPOROSIS CANDIDATE GENES: COLLAGEN TYPE Ia1 AND THE VITAMIN D RECEPTOR

VIII. SUMMARY

Measurement of Calcium, Phosphate and Magnesium

I. MEASUREMENT OF CALCIUM

II. MEASUREMENT OF PHOSPHATE

III. MEASUREMENT OF MAGNESIUM

Measurement of Parathyroid Hormone

I. ABSTRACT

II. BACKGROUND

III. DIFFERENT IMMUNOMETRIC ASSAYS FOR THE DETECTION OF PTH

IV. PRIMARY HYPERPARATHYROIDISM

V. HYPERPARATHYROIDISM IN RENAL OSTEODYSTROPHY

VI. PSEUDOHYPOPARATHYROIDISM ( PHP)

VII. CONCLUSION

New Horizons for Assessment of Vitamin D Status in Man

I. MEASUREMENT OF VITAMIN D3 ( CHOLECALCIFEROL) AND VITAMIN D2 ( ERGOCALCIFEROL)

II. MEASUREMENT OF 25- HYDROXYVITAMIN D

III. MEASUREMENT OF 1,25-DIHYDROXYVITAMIN D

Measurement of Biochemical Markers of Bone Formation

I. ABSTRACT

II. INTRODUCTION

III. PROPEPTIDES OF TYPE I PROCOLLAGEN

IV. TOTAL ALKALINE PHOSPHATASE

V. BONE ALKALINE PHOSPHATASE

VI. OSTEOCALCIN

VII. DISCUSSION

Measurement of Biochemical Markers of Bone Resorption

I. INTRODUCTION

II. COLLAGEN RELATED MARKERS

III. NON-COLLAGENOUS PROTEINS OF THE BONE MATRIX

IV. OSTECLAST ENZYMES

Variability in the Measurement of Biochemical Markers of Bone Turnover

I. INTRODUCTION

II. SOURCES OF PRE-ANALYTICAL VARIABILITY IN THE MEASUREMENT OF BIOCHEMICAL MARKERS OF BONE TURNOVER

III. STATISTICAL CONSIDERATION OF VARIABILITY

IV. SUMMARY

Validation of Biochemical Markers of Bone Turnover

I. INTRODUCTION

II. VALIDATION OF BIOCHEMICAL MARKERS BY CALCIUM KINETICS

III. VALIDATION OF BIOCHEMICAL MARKERS BY BONE HISTOMORPHOMETRY

IV. CONCLUSIONS

Genetic Markers of Joint Disease

I. INTRODUCTION

II. ANKYLOSING SPONDYLITIS

III. REACTIVE ARTHRITIS

IV. RHEUMATOID ARTHRITIS

V. JUVENILE RHEUMATOID ARTHRITIS

VI. CONCLUSION

Laboratory Assessment of Postmenopausal Osteoporosis

I. INTRODUCTION

II. POSTMENOPAUSAL BONE LOSS

III. MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS

IV. CONCLUSION

Monitoring Anabolic Treatment

I. INTRODUCTION

II. CELLULAR AND REGULATORY MECHANISMS OF THE ANABOLIC ACTIONS OF PARATHYROID HORMONE

III. PHARMACOKINETICS OF TERIPARATIDE IN HUMAN SUBJECTS

IV. ACTIONS OF PARATHYROID HORMONE TO IMPROVE BONE QUALITY

V. CONCLUSIONS

Monitoring of Antiresorptive Therapy

I. INTRODUCTION

II. EFFECTS OF PRETREATMENT BONE TURNOVER AND MINERAL DENSITY ON THERAPEUTIC OUTCOMES

III. THE ROLE OF MARKERS OF BONE TURNOVER IN MONITORING ANTIRESORPTIVE OSTEOPOROSIS THERAPY

IV. INTERPRETATION OF CHANGES IN BONE TURNOVER MARKERS

Age-related Osteoporosis and Skeletal Markers of Bone Turnover

I. INTRODUCTION

II. EPIDEMIOLOGY AND PATHOGENESIS OF AGE-RELATED OSTEOPOROSIS-RELATIONSHIP TO BONE TURNOVER

III. MARKERS OF BONE TURNOVER AND AGE-RELATED OSTEOPOROSIS-CLINICAL IMPLICATIONS

IV. SUMMARY

Steroid-Induced Osteoporosis

I. SUMMARY

II. INTRODUCTION

III. EPIDEMIOLOGY

IV. PATHOGENESIS

V. EFFECTS OF GLUCOCORTICOIDS ON HISTOLOGICAL INDICES OF BONE TURNOVER

VI. EFFECT OF GLUCOCORTICOIDS ON MARKERS OF BONE TURNOVER

VII. EVALUATION OF STEROIDTREATED PATIENTS

VIII. TREATMENT AND FOLLOW-UP

Transplantation Osteoporosis: Biochemical Correlates of Pathogenesis and Treatment

I. INTRODUCTION

II. KIDNEY TRANSPLANTATION

III. CARDIAC TRANSPLANTATION

IV. LIVER TRANSPLANTATION

V. LUNG TRANSPLANTATION

VI. BONE MARROW TRANSPLANTATION

VII. MECHANISMS OF BONE LOSS AFTER TRANSPLANTATION

VIII. PREVENTION AND MANAGEMENT OF TRANSPLANTATION OSTEOPOROSIS

IX. CONCLUSIONS

Secondary Osteoporosis

I. INTRODUCTION

II. HYPERTHYROIDISM AND OSTEOPOROSIS

III. OSTEOPOROSIS SECONDARY TO HYPOGONADISM

IV. ANTICONVULSANT DRUGS AND OSTEOPOROSIS

Osteomalacia and Rickets

I. DEFINITION

II. ETIOLOGY

III. INCIDENCE AND EPIDEMIOLOGY

IV. CALCIOPENIC RICKETS AND OSTEOMALACIA

V. PHOSPHOPENIC RICKETS AND OSTEOMALACIA

VI. NORMAL MINERAL RICKETS AND OSTEOMALACIA

Assessment of Bone and Joint Diseases: Renal Osteodystrophy

I. INTRODUCTION

II. BIOCHEMICAL ASSESSMENT OF RENAL OSTEODYSTROPHY

III. SKELETAL IMAGING IN RENAL OSTEODYSTROPHY

IV. SUMMARY

Primary Hyperparathyroidism

I. INTRODUCTION

II. ETIOLOGY

III. CLINICAL PRESENTATION

IV. BONE MARKERS IN PRIMARY HYPERPARATHYROIDISM

V. CYTOKINES IN PRIMARY HYPERPARATHYROIDISM

VI. TREATMENT OF PRIMARY HYPERPARATHYROIDISM

VII. SUMMARY

Paget’s Disease of Bone

I. INTRODUCTION

II. ETIOLOGY AND PATHOGENESIS

III. TREATMENT

Metastatic Bone Disease

I. ABSTRACT

II. INTRODUCTION

III. USE OF MARKERS OF BONE TURNOVER FOR THE DIAGNOSIS OF BONE METASTASES

IV. USE OF MARKERS OF BONE TURNOVER FOR THE MONITORING OF TUMOR BONE DISEASE

V. PREDICTION OF THE DEVELOPMENT OF BONE METASTASES

Rare Bone Diseases

I. INTRODUCTION

II. OSTEOPENIA

III. OSTEOSCLEROSIS AND HYPEROSTOSIS

IV. ECTOPIC CALCIFICATION

V. OTHER DISORDERS

Osteogenesis Imperfecta

I. INTRODUCTION

II. CLASSIFICATION

III. DIAGNOSIS

IV. DIFFERENTIAL DIAGNOSIS

V. PATHOGENESIS

VI. BISPHOSPHONATE THERAPY IN OI

VII. MEDICAL THERAPIES OTHER THAN BISPHOSPHONATES

VIII. POTENTIAL FUTURE THERAPIES

IX. CONCLUSIONS

Rheumatoid Arthritis and other Inflammatory Joint Pathologies

I. ABSTRACT

II. INTRODUCTION

III. EFFECTS OF JOINT INFLAMMATION ON SKELETAL REMODELING

IV. EFFECTS OF JOINT INFLAMMATION ON CARTILAGE REMODELING

V. CONCLUSION

Osteoarthritis and Degenerative Spine Pathologies

I. INTRODUCTION

II. CHARACTERISTICS OF OA

III. ETIOLOGY

IV. TREATMENT OPTIONS

V. CURRENT DIAGNOSTIC PROCEDURES

VI. BIOCHEMICAL ASPECTS OF OSTEOARTHRITIS

VII. MARKERS OF BONE TURNOVER

VIII. MARKERS OF CARTILAGE METABOLISM

IX. SPINE DEGENERATION AND MARKERS

X. SUMMARY

XI. CONCLUSIONS

Index

Color Plate