Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

The Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition is the comprehensive revision of the field-leading reference on bone and mineral health. Chapters look to explain basic biological factors of healthy development and disease states and make it easily translatable to clinical interventions. The new edition has been fully revised by the leading researchers and clinicians in the field to provide concise coverage of the widest possible spectrum of metabolic bone diseases and disorders of mineral metabolism.

The eighth edition of this esteemed reference expands coverage and includes exciting new features that strengthen its usefulness and ensure that the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism maintains its place as the pre-eminent reference on bone and mineral health. Features new to this edition include:

• A new section: “The Skeleton and its Integration with Other Disorders”

• New chapters covering a diverse range of topics from “Denosumab” to “Radiation-Induced   Bone Loss”

• Full-color figures throughout the text

• User-friendly chapter layout

• A new companion website with useful supplementary materials at www.asbmrprimer.com

The Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition is the definitive, one-stop reference for advanced students, clinicians, and researchers working in the field of bone health and disease.

Primer readers, don’t miss out on another valuable resource, the Journal of Bone and Mineral Research. This top-ranked and most cited journal in the field, with an impact factor of 6.373, is published monthly by the American Society for Bone and Mineral Research
(ASBMR). The JBMR publishes highly competitive original manuscripts, reviews, and special articles in basic, translational, and clinical science relevant to bone, muscle, and mineral metabolism.

RECEIVE JBMR AS AN ASBMR MEMBER
This pre-eminent journal is just one of many advantages of ASBMR membership. From grant opportunities to quality educational programming to abstract submissions and more, ASBMR membership offers you unparalleled benefits. Be sure to visit www.asbmr.org to learn how ASBMR promotes research, translates science into clinical care, and connects a worldwide audience within and beyond bone research boundaries.
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Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 8th Edition is the comprehensive revision of the field-leading reference on bone and mineral health. The eighth edition has been fully revised by the leading researchers and clinicians in the field to provide concise coverage of the widest possible spectrum of metabolic bone diseases and disorders of mineral metabolism. Chapters look to explain basic biological factors of healthy development and disease states and make it easily translatable to clinical interventions. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism is the definitive, one-stop reference for anyone working in the field of bone health and disease

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 8th Edition is the comprehensive revision of the field-leading reference on bone and mineral health. The eighth edition has been fully revised by the leading researchers and clinicians in the field to provide concise coverage of the widest possible spectrum of metabolic bone diseases and disorders of mineral metabolism. Chapters look to explain basic biological factors of healthy development and disease states and make it easily translatable to clinical interventions.

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism is the definitive, one-stop reference for anyone working in the field of bone health and disease

Contributors x

Primer Corporate Sponsors xxii

Preface to the Eighth Edition of the Primer: Clifford J. Rosen xxiii

About ASBMR xxiv

President’s Preface: Lynda F. Bonewald xxv

About the Companion Website xxvi

Section I: Molecular, Cellular, and Genetic Determinants of Bone Structure and Formation 1
Section Editor Karen M. Lyons

1 Skeletal Morphogenesis and Embryonic Development 3
Yingzi Yang

2 Signal Transduction Cascades Controlling Osteoblast Differentiation 15
David J.J. de Gorter and Peter ten Dijke

3 Osteoclast Biology and Bone Resorption 25
F. Patrick Ross

4 Osteocytes 34
Lynda F. Bonewald

5 Connective Tissue Pathways That Regulate Growth Factors 42
Gerhard Sengle and Lynn Y. Sakai

6 The Composition of Bone 49
Adele L. Boskey and Pamela Gehron Robey

7 Assessment of Bone Mass and Microarchitecture in Rodents 59
Blaine A. Christiansen

8 Animal Models: Genetic Manipulation 69
Karen M. Lyons

9 Animal Models: Allelic Determinants for BMD 76
Robert D. Blank

10 Neuronal Regulation of Bone Remodeling 82
Florent Elefteriou and Gerard Karsenty

11 Skeletal Healing 90
Michael J. Zuscik

12 Biomechanics of Fracture Healing 99
Elise F. Morgan and Thomas A. Einhorn

13 Human Genome-Wide Association (GWA) Studies 106
Douglas P. Kiel

14 Circulating Osteogenic Cells 111
Robert J. Pignolo and Moustapha Kassem

Section II: Skeletal Physiology 119
Section Editor Ego Seeman

15 Human Fetal and Neonatal Bone Development 121
Tao Yang, Monica Grover, Kyu Sang Joeng, and Brendan Lee

16 Skeletal Growth and Peak Bone Strength 127
Qingju Wang and Ego Seeman

17 Ethnic Differences in Bone Acquisition 135
Shane A. Norris, Lisa K. Micklesfi eld, and John M. Pettifor

18 Calcium and Other Nutrients During Growth 142
Tania Winzenberg and Graeme Jones

19 Growing a Healthy Skeleton: The Importance of Mechanical Loading 149
Mark R. Forwood

20 Pregnancy and Lactation 156
Christopher S. Kovacs and Henry M. Kronenberg

21 Menopause 165
Ian R. Reid

Section III: Mineral Homeostasis 171
Section Editor Ego Seeman

22 Regulation of Calcium and Magnesium 173
Murray J. Favus and David Goltzman

23 Fetal Calcium Metabolism 180
Christopher S. Kovacs

24 Fibroblast Growth Factor-23 (FGF23) 188
Kenneth E. White and Michael J. Econs

25 Gonadal Steroids 195
Stavros C. Manolagas, Maria Almeida, and Robert L. Jilka

26 Parathyroid Hormone 208
Robert A. Nissenson and Harald Jüppner

27 Parathyroid Hormone-Related Protein 215
John J. Wysolmerski

28 Ca2+-Sensing Receptor 224
Edward M. Brown

29 Vitamin D: Production, Metabolism, Mechanism of Action, and Clinical Requirements 235
Daniel Bikle, John S. Adams, and Sylvia Christakos

Section IV: Investigation of Metabolic Bone Diseases 249
Section Editor Douglas C. Bauer

30 DXA in Adults and Children 251
Glen Blake, Judith E. Adams, and Nick Bishop

31 Quantitative Computed Tomography in Children and Adults 264
C.C. Glüer

32 Magnetic Resonance Imaging of Bone 277
Sharmila Majumdar

33 Radionuclide Scintigraphy in Metabolic Bone Disease 283
Gary J.R. Cook, Gopinath Gnanasegaran, and Ignac Fogelman

34 FRAX®: Assessment of Fracture Risk 289
John A Kanis

35 Biochemical Markers of Bone Turnover in Osteoporosis 297
Pawel Szulc, Douglas C. Bauer, and Richard Eastell

36 Bone Biopsy and Histomorphometry in Clinical Practice 307
Robert R. Recker

37 Diagnosis and Classifi cation of Vertebral Fracture 317
James F. Griffi th, Judith E. Adams, and Harry K. Genant

38 Approaches to Genetic Testing 336
Christina Jacobsen, Yiping Shen, and Ingrid A. Holm

Section V: Osteoporosis 343
Section Editors Paul D. Miller and Socrates E. Papapoulos

39 Osteoporosis Overview 345
Michael Kleerekoper

40 The Epidemiology of Osteoporotic Fractures 348
Nicholas Harvey, Elaine Dennison, and Cyrus Cooper

41 Overview of Pathogenesis 357
Ian R. Reid

42 Nutrition and Osteoporosis 361
Connie M. Weaver and Robert P. Heaney

43 The Role of Sex Steroids in the Pathogenesis of Osteoporosis 367
Matthew T. Drake and Sundeep Khosla

44 Translational Genetics of Osteoporosis: From Population Association to Individualized Prognosis 376
Bich H. Tran, Jacqueline R. Center, and Tuan V. Nguyen

45 Prevention of Falls 389
Heike A. Bischoff-Ferrari

46 Exercise and the Prevention of Osteoporosis 396
Clinton T. Rubin, Janet Rubin, and Stefan Judex

47 Calcium and Vitamin D 403
Bess Dawson-Hughes

48 Estrogens, Estrogen Agonists/Antagonists, and Calcitonin 408
Nelson B. Watts

49 Bisphosphonates for Postmenopausal Osteoporosis 412
Socrates E. Papapoulos

50 Denosumab 420
Michael R. McClung

51 Parathyroid Hormone Treatment for Osteoporosis 428
Felicia Cosman and Susan L. Greenspan

52 Strontium Ranelate in the Prevention of Osteoporotic Fractures 437
René Rizzoli

53 Combination Anabolic and Antiresorptive Therapy for Osteoporosis 444
John P. Bilezikian and Natalie E. Cusano

54 Compliance and Persistence with Osteoporosis Medications 448
Deborah T. Gold

55 Cost-Effectiveness of Osteoporosis Treatment 455
Anna N.A. Tosteson

56 Future Therapies of Osteoporosis 461
Kong Wah Ng and T. John Martin

57 Juvenile Osteoporosis 468
Nick Bishop and Francis H. Glorieux

58 Glucocorticoid-Induced Bone Disease 473
Robert S. Weinstein

59 Inflammation-Induced Bone Loss in the Rheumatic Diseases 482
Steven R. Goldring

60 Secondary Osteoporosis: Other Causes 489
Neveen A.T. Hamdy

61 Transplantation Osteoporosis 495
Peter R. Ebeling

62 Osteoporosis in Men 508
Eric S. Orwoll

63 Premenopausal Osteoporosis 514
Adi Cohen and Elizabeth Shane

64 Skeletal Effects of Drugs 520
Juliet Compston

65 Orthopedic Surgical Principles of Fracture Management 527
Manoj Ramachandran and David G. Little

66 Abnormalities in Bone and Calcium Metabolism After Burns 531
Gordon L. Klein

Section VI: Disorders of Mineral Homeostasis 535
Section Editors Marie Demay and Suzanne M. Jan de Beur

67 Approach to Parathyroid Disorders 537
John P. Bilezikian

68 Primary Hyperparathyroidism 543
Shonni J. Silverberg

69 Familial Primary Hyperparathyroidism (Including MEN, FHH, and HPT-JT) 553
Andrew Arnold and Stephen J. Marx

70 Non-Parathyroid Hypercalcemia 562
Mara J. Horwitz, Steven P. Hodak, and Andrew F. Stewart

71 Hypocalcemia: Defi nition, Etiology, Pathogenesis, Diagnosis, and Management 572
Anne L. Schafer and Dolores Shoback

72 Hypoparathyroidism and Pseudohypoparathyroidism 579
Mishaela R. Rubin and Michael A. Levine

73 Pseudohypoparathyroidism 590
Harald Jüppner and Murat Bastepe

74 Disorders of Phosphate Homeostasis 601
Mary D. Ruppe and Suzanne M. Jan de Beur

75 Vitamin D–Related Disorders 613
Paul Lips, Natasja M. van Schoor, and Nathalie Bravenboer

76 Vitamin D Insuffi ciency and Defi ciency 624
J. Christopher Gallagher

77 Pathophysiology of Chronic Kidney Disease Mineral Bone Disorder (CKD–MBD) 632
Keith A. Hruska and Michael Seifert

78 Treatment of Chronic Kidney Disease Mineral Bone Disorder (CKD–MBD) 640
Hala M. Alshayeb and L. Darryl Quarles

79 Disorders of Mineral Metabolism in Childhood 651
Thomas O. Carpenter

80 Paget’s Disease of Bone 659
Ethel S. Siris and G. David Roodman

Section VII: Cancer and Bone 669
Section Editor Theresa A. Guise

81 Overview of Mechanisms in Cancer Metastases to Bone 671
Gregory A. Clines

82 Clinical and Preclinical Imaging in Osseous Metastatic Disease 677
Geertje van der Horst and Gabri van der Pluijm

83 Metastatic Solid Tumors to Bone 686
Rachelle W. Johnson and Julie A. Sterling

84 Hematologic Malignancies and Bone 694
Rebecca Silbermann and G. David Roodman

85 Osteogenic Osteosarcoma 702
Jianning Tao, Yangjin Bae, Lisa L. Wang, and Brendan Lee

86 Skeletal Complications of Breast and Prostate Cancer Therapies 711
Catherine Van Poznak and Pamela Taxel

87 Bone Cancer and Pain 720
Patrick W. O’Donnell and Denis R. Clohisy

88 Radiation Therapy-Induced Osteoporosis 728
Jeffrey S. Willey, Shane A.J. Lloyd, and Ted A. Bateman

89 Skeletal Complications of Childhood Cancer 734
Ingrid A. Holm

90 Treatment and Prevention of Bone Metastases and Myeloma Bone Disease 741
Jean-Jacques Body

91 Radiotherapy of Skeletal Metastases 754
Edward Chow, Luluel M. Khan, and Øyvind S. Bruland

92 Concepts and Surgical Treatment of Metastatic Bone Disease 760
Kristy Weber and Scott L. Kominsky

Section VIII: Sclerosing and Dysplastic Bone Diseases 767
Section Editor Richard W. Keen

93 Sclerosing Bone Disorders 769
Michael P. Whyte

94 Fibrous Dysplasia 786
Michael T. Collins, Mara Riminucci, and Paolo Bianco

95 Osteochondrodysplasias 794
Yasemin Alanay and David L. Rimoin

96 Ischemic and Infi ltrative Disorders 805
Richard W. Keen

97 Tumoral Calcinosis—Dermatomyositis 810
Nicholas Shaw

98 Fibrodysplasia Ossifi cans Progressiva 815
Frederick S. Kaplan, Robert J. Pignolo, and Eileen M. Shore

99 Osteogenesis Imperfecta 822
Joan C. Marini

100 Skeletal Manifestations in Marfan Syndrome and Related Disorders of the Connective Tissue 830
Emilio Arteaga-Solis and Francesco Ramirez

101 Enzyme Defects and the Skeleton 838
Michael P. Whyte

Section IX: Approach to Nephrolithiasis 843
Section Editor Rajesh V. Thakker

102 Renal Tubular Physiology of Calcium Excretion 845
Peter A. Friedman and David A. Bushinsky

103 Epidemiology of Nephrolithiasis 856
Murray J. Favus

104 Diagnosis and Evaluation of Nephrolithiasis 860
Stephen J. Knohl and Steven J. Scheinman

105 Kidney Stones in the Pediatric Patient 869
Amy E. Bobrowski and Craig B. Langman

106 Treatment of Renal Stones 878
John R. Asplin

107 Genetic Basis of Renal Stones 884
Rajesh V. Thakker

Section X: Oral and Maxillofacial Biology and Pathology 893
Section Editor Laurie K. McCauley

108 Development of the Craniofacial Skeleton 895
Maiko Matsui and John Klingensmith

109 Development and Structure of Teeth and Periodontal Tissues 904
Petros Papagerakis and Thimios Mitsiadis

110 Craniofacial Disorders Affecting the Dentition: Genetic 914
Yong-Hee P. Chun, Paul H. Krebsbach, and James P. Simmer

111 Pathology of the Hard Tissues of the Jaws 922
Paul C. Edwards

112 Bisphosphonate-Associated Osteonecrosis of the Jaws 929
Hani H. Mawardi, Nathaniel S. Treister, and Sook-Bin Woo

113 Periodontal Diseases and Oral Bone Loss 941
Mary G. Lee and Keith L. Kirkwood

114 Oral Manifestations of Metabolic Bone Diseases 948
Roberto Civitelli and Charles Hildebolt

Section XI: The Skeleton and Its Integration with Other Tissues 959
Section Editor Mone Zaidi

115 Central Neuronal Control of Bone Remodeling 961
Shu Takeda and Paul Baldock

116 The Pituitary–Bone Connection 969
Mone Zaidi, Tony Yuen, Li Sun, Terry F. Davies, Alberta Zallone, and Harry C. Blair

117 Skeletal Muscle Effects on the Skeleton 978
William J. Evans

118 Glucose Control and Integration by the Skeleton 986
Patricia Ducy and Gerard Karsenty

119 Obesity and Skeletal Mass 993
Sue Shapses and Deeptha Sukumar

120 Neuropsychiatric Disorders and the Skeleton 1002
Itai Bab and Raz Yirmiya

121 Vascular Disease and the Skeleton 1012
Dwight A. Towler

122 Spinal Cord Injury: Skeletal Pathophysiology and Clinical Issues 1018
William A. Bauman and Christopher P. Cardozo

123 Hematopoiesis and Bone 1028
Benjamin J. Frisch and Laura M. Calvi

124 Bone and Immune Cell Interactions 1036
Brendan F. Boyce

Index 1043