Dynamics of Bone and Cartilage Metabolism

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ISBN: 9780120885626 | 012088562X
Cover: Hardcover
Copyright: 7/24/2006

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This updated edition is a comprehensive treatise that spans the complete range of basic biochemistry of bone and cartilage components to the clinical evaluation of disease markers in bone and joint disorders. With contributions from over 75 international experts, this latest edition is indispensable reading for those involved in skeletal research as well as for rheumatologists, endocrinologists, clinical biochemists, and other clinical disciplines participating in the management of patients with bone and cartilage diseases. *Part I provides an up-to-date account of current knowledge of the structure, biosynthesis and molecular biology of the major tissue components *Part II covers the organizational structure and cellular metabolism of bone and cartilage *Part III deals with the utility of components specific to bone and cartilage as biomarkers of health and disease

Contributors

xiii

Preface

xix

Part I Components of the Organic Extracellular Matrix of Bone and Cartilage

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

Klaus von der Mark

Introduction

(2)

The Collagen Families

(2)

Bone Collagens

(2)

Cartilage Collagens

(5)

Collagen Biosynthesis

(3)

Collagen Genes and Transcriptional Regulation

(4)

Factors Regulating Collagen Biosynthesis

(4)

Conclusions

(16)

References

(15)

Fibrillogenesis and Maturation of Collagens

Simon P. Robins

Introduction

(1)

Fibrillogenesis

(2)

Cross-linking

(6)

Concluding Remarks

(5)

References

(5)

Vitamin K Dependent Proteins of Bone and Cartilage

Caren M. Gundberg

Satoru K. Nishimoto

Abstract

(1)

Introduction

(1)

Osteocalcin

(3)

Matrix Gla Protein

(4)

Gas6

(1)

Vitamin K/Warfarin

(7)

References

(6)

Noncollagenous Proteins; Glycoproteins and Related Proteins

Dick Heinegard

Pilar Lorenzo

Tore Saxne

Introduction

(1)

Cartilage Extracellular Matrix

(5)

Bone, Extracellular Matrix

(2)

Concluding Remarks

(6)

References

(5)

Proteoglycans and Glycosaminoglycans

Tim Hardingham

Introduction

(1)

Glycosaminoglycans

(1)

Proteoglycans in Cartilage

(1)

Aggrecan

(5)

Leucine-rich Proteoglycans in Cartilage and Bone

(3)

Perlecan in Cartilage

(3)

References

(3)

Growth Factors

Philippa Hulley

Graham Russell

Peter Croucher

Introduction

(1)

Insulin-like Growth Factors

(1)

The Transforming Growth Factor-Beta/Bone Morphogenetic Protein Superfamily

100

(3)

Fibroblast Growth Factors

103

(1)

Wnts

104

(1)

Additional Growth Factors

105

(1)

Summary

106

(9)

References

107

(8)

Prostaglandins and Proinflammatory Cytokines

Lawrence G. Raisz

Joseph A. Lorenzo

Introduction

115

(1)

Prostaglandins

115

(2)

The Role that Cytokines have in Osteoclast Formation and Function

117

(1)

The Role that Proinflammatory Cytokines have in Bone and Cartilage Metabolism

118

(11)

References

121

(8)

Integrins and Other Adhesion Molecules

M. H. Helfrich

M. A. Horton

Abstract

129

(1)

Introduction

129

(1)

Molecular Structure of Adhesion Molecules

130

(4)

Adhesion Molecules in Cells of the Osteoblast Lineage

134

(5)

Adhesion Molecules in Osteoclasts

139

(3)

Adhesion Molecules in Chondrocytes

142

(2)

Conclusion

144

(9)

References

144

(9)

Alkaline Phosphatases

Jose Luis Millan

Introduction

153

(1)

Structure and Regulation of the TNAP Gene

153

(2)

Protein Structure

155

(2)

Function of TNAP

157

(3)

Clinical Use

160

(5)

References

161

(4)

Acid Phosphatases

Helena Kaija

Lila O.T. Patrikainen

Sari L. Alatalo

H. Kalervo Vaananen

Pirkko T. Vihko

Acid Phosphatases

165

(1)

Tartrate-Resistant Acid Phosphatase (TRACP)

166

(7)

Prostatic Acid Phosphatase (PAP)

173

(8)

References

176

(5)

Matrix Proteinases

Ian M. Clark

Gillian Murphy

Introduction

181

(1)

Aspartic Proteinases

181

(1)

Cysteine Proteinases

182

(2)

Serine Proteinases

184

(2)

Metalloproteinases

186

(15)

References

192

(9)

Part II Structure and Metabolism of the Extracellular Matrix of Bone and Cartilage

Mineralization, Structure and Function of Bone

Adele L. Boskey

Abstract

201

(1)

The Structure and Function of Bone

201

(3)

Bone Mineralization

204

(5)

Bone Modeling and Remodeling

209

(4)

References

209

(4)

Bone Structure and Strength

Ego Seeman

Introduction

213

(1)

Gravity and the Need for Stiffness, Flexibility, Lightness and Speed

213

(1)

The Material Composition and Structural Design of Bone

214

(2)

Bone Modeling and Remodeling -- The Mechanism of Bone's Construction during Growth and Decay with Advancing Age

216

(1)

Strength Maintenance

217

(2)

Conclusion

219

(2)

References

219

(2)

The Cells of Bone

Jane B. Lian

Gary S. Stein

Abstract

221

(1)

Introduction

221

(1)

Developmental Signals for Cartilage and Bone Tissue Formation

222

(5)

Osteogenic Lineage Cells

227

(9)

The Osteoclast: A Functionally Unique Cell for Physiologically Regulated Resorption of Bone Mineral

236

(6)

Perspectives

242

(17)

References

242

(17)

Signaling in Bone

T. John Martin

Natalie A. Sims

Abstract

259

(1)

Introduction

259

(1)

The Control of Osteoclasts

260

(1)

Signaling in the Control of Osteoclast Activity

261

(1)

Signals from the Osteoblast Lineage that Control Osteoclast Formation

261

(1)

Hormone and Cytokine Influences on the Contact-dependent Regulation of Osteoclasts

261

(1)

Discovery of the Physiological Signaling Mechanisms in Osteoclast Control

262

(1)

Rank Signaling

263

(1)

Coupling of Bone Formation to Resorption -- Release of Growth Factors from bone Matrix

264

(2)

Coupling of Bone Formation to Resorption -- Autocrine/Paracrine Regulation by Differentiating Osteoblasts

266

(1)

Coupling of Bone Formation to Resorption -- Are Osteoclasts a Source of Coupling Activity?

266

(7)

References

267

(6)

Parathyroid Hormone: Structure, Function and Dynamic Actions

Lorraine A. Fitzpatrick

John P. Bilezikian

Introduction

273

(1)

Structure of the PTH Gene

273

(1)

Chromosome Location

274

(1)

Control of Gene Expression

275

(3)

Biosynthesis of Parathyroid Hormone

278

(1)

Metabolism of Parathyroid Hormone

278

(1)

Receptor Interactions of Parathyroid Hormone and Parathyroid Hormone-Related Protein

279

(1)

Structure of the PTH/PTHrP (PTH1R) Receptor

279

(2)

Activation of the Cyclic Adenosine Monophosphate Second-Messenger System by Parathyroid Hormone

281

(1)

Identification of a Second PTH Receptor

282

(1)

Physiological Actions of PTH

282

(2)

Cell-to-Cell Communication: Osteoblasts and Osteoclasts

284

(1)

Preferential Actions of PTH at Selected Skeletal Sites

285

(8)

References

287

(6)

Interaction of Parathyroid Hormone-related Peptide with the Skeleton

David Goltzman

Abstract

293

(1)

Introduction

293

(1)

Molecular Biology and Mechanism of Action

294

(4)

The Skeletal Actions of PTHrP

298

(3)

Summary

301

(6)

References

302

(5)

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

Geert Carmeliet

Annemieke Verstuyf

Christa Maes

Guy Eelen

Roger Bouillon

Introduction

307

(1)

Metabolism of Vitamin D

308

(1)

Nuclear Vitamin D Receptor

309

(3)

Vitamin D and Bone Cells

312

(2)

Pathology and Therapy Related to Vitamin D Availability, Metabolism, and Function

314

(5)

Conclusions

319

(8)

References

319

(8)

Sex Steroid Effects on Bone Metabolism

David G. Monroe

Thomas C. Spelsberg

S. Khosla

Abstract

327

(1)

Introduction

327

(1)

Molecular Structures, Synthesis, Mechanism of Action of Major Sex Steroids, and Transcriptional Coregulator Function

328

(3)

Effects of Sex Steroids on Bone Cells and Bone Turnover

331

(4)

Effects of Estrogens and Androgens on Bone Metabolism in Men Versus Women

335

(1)

Effects of Sex Steroids on Extraskeletal Calcium Homeostasis

336

(1)

Summary

337

(8)

References

338

(7)

Physiology of Calcium and Phosphate Homeostases

Rene Rizzoli

Jean-Philippe Bonjour

Abstract

345

(1)

Introduction

345

(1)

Body Distribution of Calcium

346

(1)

Determinants of Extracellular Calcium Concentration

346

(3)

Relative Importance of the Various Calcium Fluxes in Controlling Extracellular Calcium Homeostasis

349

(1)

Homeostatic Responses to Hypocalcemia

349

(3)

Calcium and Bone Growth

352

(1)

Body Distribution of Phosphorus

353

(1)

Determinants of Extracellular Phosphate Concentration

353

(3)

Homeostatic Responses to Changes in Phosphate Supply or Demand

356

(1)

Conclusions

357

(4)

References

357

(4)

The Central Control of Bone Remodeling

Paul A. Baldock

Susan J. Allison

Herbert Herzog

Edith M. Gardiner

Introduction

361

(1)

Actions of Leptin

362

(3)

Sympathetic Nervous System

365

(4)

Neuropeptide Y and the Y Receptors

369

(2)

Interaction between Leptin and Y2-Regulated Bone Antiosteogenic Pathways

371

(2)

Concluding Remarks

373

(4)

References

373

(4)

New Concepts in Bone Remodeling

David W. Dempster

Hua Zhou

Introduction

377

(1)

An Overview of the Remodeling Cycle

377

(3)

Functions of Bone Remodeling

380

(1)

The Role of Apoptosis in Regulating Bone Balance

381

(2)

Possible Mechanisms whereby a Reduction in Activation Frequency may Protect against Fracture

383

(8)

References

386

(5)

Products of Bone Collagen Metabolism

Juha Risteli

Leila Risteli

Introduction

391

(1)

Products of Bone Collagen Synthesis, the Procollagen Propeptides

392

(5)

Degradation Products of Type I Collagen

397

(5)

Closing Remarks

402

(5)

References

403

(4)

Supramolecular Structure of Cartilage Matrix

Peter Bruckner

Summary

407

(1)

Introduction

407

(1)

Light and Electron Micrography

408

(1)

Biochemistry of Cartilage

409

(2)

Studies of Fibril Structures by X-ray Diffraction

411

(1)

Structure of Fibril Fragments Obtained by Mechanical Disruption of Tissue

411

(1)

Studies of Collagen Cross-linking in Cartilage Fibrils

412

(1)

Reconstitution of Aggregates from Soluble Collagens and other Macromolecules

412

(2)

Studies of Transgenic Mice and of Human Genetic Matrix Diseases

414

(1)

Correlating Structure With the Biomechanical Role of Articular Cartilage

415

(1)

Models of Cartilage Fibril Structure

416

(1)

Future Perspectives

417

(4)

References

418

(3)

Products of Cartilage Metabolism

Daniel-Henri Manicourt

Jean-Pierre Devogelaer

Eugene J.-M. A. Thonar

Introduction

421

(1)

The Chondrocyte and its Extracellular Matrix

422

(2)

Products of Collagen Metabolism

424

(5)

Products of Aggrecan Metabolism

429

(5)

Products of the Metabolism of other Proteoglycans

434

(1)

Products of the Metabolism of Link Protein and Hyaluronan

435

(2)

Other Products of Chondrocyte Metabolism

437

(1)

Concluding Statement

438

(13)

References

439

(12)

Fluid Dynamics of the Joint Space and Trafficking of Matrix Products

Peter A. Simkin

Introduction

451

(1)

Interpretation of Marker Data and Strategies for Dealing with Them

451

(5)

Conclusion

456

(1)

References

456

(1)

Transgenic Models of Bone Disease

Barbara E. Kream

John R. Harrison

Introduction

457

(1)

Generation of Mouse Models

457

(3)

Transgenic Models in Bone Biology

460

(5)

Perspectives and Future Directions

465

(6)

References

465

(6)

Part III Markers of Bone and Cartilage Metabolism

The Role of Genetic Variation in Osteoporosis

Andre G. Uitterlinden

Joyce B.J. van Meurs

Fernando Rivadeneira

Johannes P.T.M. van Leeuwen

Huibert A.P. Pols

Abstract

471

(1)

Osteoporosis has Genetic Influences

471

(2)

Genome-wide Approaches to Find the Genes

473

(3)

Association Analysis of Candidate Gene Polymorphisms

476

(2)

Haplotypes

478

(2)

Meta-analyses

480

(2)

Osteoporosis Candidate Genes: Collagen Type Iα1 and the Vitamin D Receptor

482

(1)

Summary

483

(4)

References

484

(3)

Measurement of Calcium, Phosphate and Magnesium

Heinrich Schmidt-Gayk

Measurement of Calcium

487

(8)

Measurement of Phosphate

495

(4)

Measurement of Magnesium

499

(8)

References

502

(5)

Measurement of Parathyroid Hormone

Harald Juppner

Ghada El-Hajj Fuleihan

Abstract

507

(1)

Background

507

(2)

Different Immunometric Assays for the Detection of PTH

509

(1)

Primary Hyperparathyroidism

510

(1)

Hyperparathyroidism in Renal Osteodystrophy

510

(1)

Pseudohypoparathyroidism (PHP)

510

(1)

Conclusion

511

(2)

References

511

(2)

New Horizons for Assessment of Vitamin D Status in Man

Gary L. Lensmeyer

Neil Binkley

Marc K. Drezner

Measurement of Vitamin D3 (Cholecalciferol) and Vitamin D2 (Ergocalciferol)

513

(1)

Measurement of 25-Hydroxyvitamin D

513

(11)

Measurement of 1,25-Dihydroxyvitamin D

524

(5)

References

525

(4)

Measurement of Biochemical Markers of Bone Formation

Kim E. Naylor

Richard Eastell

Abstract

529

(1)

Introduction

529

(1)

Propeptides of Type I Procollagen

530

(3)

Total Alkaline Phosphatase

533

(1)

Bone Alkaline Phosphatase

533

(2)

Osteocalcin

535

(2)

Discussion

537

(4)

References

537

(4)

Measurement of Biochemical Markers of Bone Resorption

Marius E. Kraenzlin

Markus J. Seibel

Introduction

541

(2)

Collagen Related Markers

543

(10)

Non-Collagenous Proteins of the Bone Matrix

553

(2)

Osteclast Enzymes

555

(10)

References

557

(8)

Variability in the Measurement of Biochemical Markers of Bone Turnover

Tuan V. Nguyen

Christian Meier

Markus J. Seibel

Introduction

565

(1)

Sources of Pre-Analytical Variability in the Measurement of Biochemical Markers of Bone Turnover

566

(5)

Statistical Consideration of Variability

571

(6)

Summary

577

(6)

References

578

(5)

Validation of Biochemical Markers of Bone Turnover

Kim Brixen

Erik Fink Eriksen

Introduction

583

(1)

Validation of Biochemical Markers by Calcium Kinetics

584

(4)

Validation of Biochemical Markers by Bone Histomorphometry

588

(4)

Conclusions

592

(3)

References

592

(3)

Genetic Markers of Joint Disease

Michel Neidhart

Renate E. Gay

Steffen Gay

Introduction

595

(1)

Ankylosing Spondylitis

595

(2)

Reactive Arthritis

597

(1)

Rheumatoid Arthritis

598

(7)

Juvenile Rheumatoid Arthritis

605

(1)

Conclusion

606

(5)

References

606

(5)

Laboratory Assessment of Postmenopausal Osteoporosis

Patrick Garnero

Pierre D. Delmas

Introduction

611

(1)

Postmenopausal Bone Loss

612

(4)

Management of Postmenopausal Osteoporosis

616

(8)

Conclusion

624

(5)

References

624

(5)

Monitoring Anabolic Treatment

John P. Bilezikian

Mishaela R. Rubin

Introduction

629

(1)

Cellular and Regulatory Mechanisms of the Anabolic Actions of Parathyroid Hormone

630

(1)

Pharmacokinetics of Teriparatide in Human Subjects

631

(1)

Actions of Parathyroid Hormone to Improve Bone Quality

632

(10)

Conclusions

642

(7)

References

642

(7)

Monitoring of Antiresorptive Therapy

Christian Meier

Tuan V. Nguyen

Markus J. Seibel

Introduction

649

(1)

Effects of Pretreatment Bone Turnover and Mineral Density on Therapeutic Outcomes

650

(1)

The Role of Markers of Bone Turnover in Monitoring Antiresorptive Osteoporosis Therapy

651

(10)

Interpretation of Changes in Bone Turnover Markers

661

(10)

References

665

(6)

Age-related Osteoporosis and Skeletal Markers of Bone Turnover

Clifford J. Rosen

Introduction

671

(1)

Epidemiology and Pathogenesis of Age-Related Osteoporosis-Relationship to Bone Turnover

672

(7)

Markers of Bone Turnover and Age-Related Osteoporosis - Clinical Implications

679

(4)

Summary

683

(6)

References

683

(6)

Steroid-Induced Osteoporosis

Ian R. Reid

Summary

689

(1)

Introduction

689

(1)

Epidemiology

689

(1)

Pathogenesis

690

(1)

Effects of Glucocorticoids on Histological Indices of Bone Turnover

691

(1)

Effect of Glucocorticoids on Markers of Bone Turnover

692

(2)

Evaluation of Steroid-Treated Patients

694

(1)

Treatment and Follow-up

694

(7)

References

695

(6)

Transplantation Osteoporosis: Biochemical Correlates of Pathogenesis and Treatment

Carolina A. Moreira Kulak

Elizabeth Shane

Introduction

701

(1)

Kidney Transplantation

702

(3)

Cardiac Transplantation

705

(1)

Liver Transplantation

706

(1)

Lung Transplantation

706

(1)

Bone Marrow Transplantation

707

(1)

Mechanisms of Bone Loss After Transplantation

707

(2)

Prevention and Management of Transplantation Osteoporosis

709

(2)

Conclusions

711

(6)

References

711

(6)

Secondary Osteoporosis

Jean E. Mulder

Carolina A. Moreira Kulak

Elizabeth Shane

Introduction

717

(1)

Hyperthyroidism and Osteoporosis

717

(7)

Osteoporosis Secondary to Hypogonadism

724

(6)

Anticonvulsant Drugs and Osteoporosis

730

(9)

References

732

(7)

Osteomalacia and Rickets

Marc K. Drezner

Definition

739

(2)

Etiology

741

(1)

Incidence and Epidemiology

742

(1)

Calciopenic Rickets and Osteomalacia

743

(4)

Phosphopenic Rickets and Osteomalacia

747

(3)

Normal Mineral Rickets and Osteomalacia

750

(5)

References

751

(4)

Assessment of Bone and Joint Diseases: Renal Osteodystrophy

Esther A. Gonzalez

Ziyad Al Aly

Kevin J. Martin

Introduction

755

(2)

Biochemical Assessment of Renal Osteodystrophy

757

(4)

Skeletal Imaging in Renal Osteodystrophy

761

(1)

Summary

762

(5)

References

762

(5)

Primary Hyperparathyroidism

Shonni J. Silverberg

John P. Bilezikian

Introduction

767

(1)

Etiology

767

(1)

Clinical Presentation

768

(2)

Bone Markers in Primary Hyperparathyroidism

770

(2)

Cytokines in Primary Hyperparathyroidism

772

(1)

Treatment of Primary Hyperparathyroidism

772

(3)

Summary

775

(4)

References

775

(4)

Paget's Disease of Bone

Andreas Grauer

Ethel Siris

Stuart Ralston

Introduction

779

(1)

Etiology and Pathogenesis

779

(5)

Treatment

784

(9)

References

788

(5)

Metastatic Bone Disease

Jean-Jacques Body

Abstract

793

(1)

Introduction

794

(2)

Use of Markers of Bone Turnover for the Diagnosis of Bone Metastases

796

(6)

Use of Markers of Bone Turnover for the Monitoring of Tumor Bone Disease

802

(4)

Prediction of the Development of Bone Metastases

806

(5)

References

806

(5)

Rare Bone Diseases

Michael P. Whyte

Introduction

811

(1)

Osteopenia

812

(5)

Osteosclerosis and Hyperostosis

817

(6)

Ectopic Calcification

823

(2)

Other Disorders

825

(6)

References

826

(5)

Osteogenesis Imperfecta

Francis H. Glorieux

Frank Rauch

Introduction

831

(1)

Classification

832

(1)

Diagnosis

833

(1)

Differential Diagnosis

834

(1)

Pathogenesis

834

(1)

Bisphosphonate Therapy in OI

835

(3)

Medical Therapies Other than Bisphosphonates

838

(1)

Potential Future Therapies

839

(1)

Conclusions

839

(4)

References

839

(4)

Rheumatoid Arthritis and other Inflammatory Joint Pathologies

Steven R. Goldring

Mary B. Goldring

Abstract

843

(1)

Introduction

843

(1)

Effects of Joint Inflammation on Skeletal Remodeling

844

(8)

Effects of Joint Inflammation on Cartilage Remodeling

852

(6)

Conclusion

858

(13)

References

858

(13)

Osteoarthritis and Degenerative Spine Pathologies

Kristina Akesson

Introduction

871

(1)

Characteristics of OA

872

(1)

Etiology

872

(1)

Treatment Options

873

(1)

Current Diagnostic Procedures

873

(1)

Biochemical Aspects of Osteoarthritis

873

(1)

Markers of Bone Turnover

874

(4)

Markers of Cartilage Metabolism

878

(4)

Spine Degeneration and Markers

882

(1)

Summary

883

(1)

Conclusions

884

(1)

References

884

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Dynamics of Bone and Cartilage Metabolism

Summary

Table of Contents

Supplemental Materials