Table of Contents

Contributors xi

Preface to the Ninth Edition of the Primer:
John P. Bilezikian xxiv

About ASBMR xxv

President’s Preface Michael J. Econs xxvi

About the Companion Website xxvii

Section I Molecular and Cellular Determinants of Bone Structure and Function 1
Section Editor Karen Lyons

1 Early Skeletal Morphogenesis in Embryonic Development 3
Yingzi Yang

2 Endochondral Ossification 12
Courtney M. Karner and Matthew J. Hilton

3 Local and Circulating Osteoprogenitor Cells and Lineages 20
Naomi Dirckx and Christa Maes

4 Osteoblasts Function, Development, and Regulation 31
Elizabeth W. Bradley, Jennifer J. Westendorf, Andre J. van Wijnen, and Amel Dudakovic

5 Osteocytes 38
Lynda F. Bonewald

6 Osteoclast Biology and Bone Resorption 46
Hiroshi Takayanagi

7 Signal Transduction Cascades Controlling Osteoblast Differentiation 54
David J.J. de Gorter, Gonzalo Sánchez‐Duffhues, and Peter ten Dijke

8 The TGF‐β Superfamily in Bone Formation and Maintenance 60
Ce Shi and Yuji Mishina

9 Recent Developments in Understanding the Role of Wnt Signaling in Skeletal Development and Disease 68
Zhendong A. Zhong, Nicole J. Ethen, and Bart O. Williams

10 Mechanotransduction in Bone Formation and Maintenance 75
Whitney A. Bullock, Lilian I. Plotkin, Alexander G. Robling, and Fredrick M. Pavalko

11 The Composition of Bone 84
Adele L. Boskey and Pamela G. Robey

12 Assessment of Bone Mass, Structure, and Quality in Rodents 93
Jeffry S. Nyman and Deepak Vashishth

13 Skeletal Healing Cellular and Molecular Determinants 101
Alayna E. Loiselle and Michael J. Zuscik

14 Biomechanics of Fracture Healing 108
Elise F. Morgan, Amira I. Hussein, and Thomas A. Einhorn

Section II Skeletal Physiology 115
Section Editor Ego Seeman

15 Human Fetal and Neonatal Bone Development 117
Tao Yang, Monica Grover, Kyu Sang Joeng, and Brendan Lee

16 Skeletal Growth a Major Determinant of Bone’s Structural Diversity in Women and Men 123
Ego Seeman

17 Racial Differences in the Acquisition and Age‐related Loss of Bone Strength 131
Shane A. Norris, Marcella D. Walker, Kate Ward, Lisa K. Micklesfield, and John M. Pettifor

18 Calcium, Vitamin D, and Other Nutrients During Growth 135
Tania Winzenberg and Graeme Jones

19 Mechanical Loading and the Developing Skeleton 141
Mark R. Forwood

20 Pregnancy and Lactation 147
Christopher S. Kovacs and Henry M. Kronenberg

21 Menopause and Age‐related Bone Loss 155
Carlos M. Isales and Ego Seeman

Section III Mineral Homeostasis 163
Section Editors David Goltzman and Harald Jüppner

22 Regulation of Calcium Homeostasis 165
Line Vautour and David Goltzman

23 Magnesium Homeostasis 173
Aliya Aziz Khan, Asiya Sbayi, and Karl Peter Schlingmann

24 Fetal Calcium Metabolism 179
Christopher S. Kovacs

25 FGF23 and the Regulation of Phosphorus Metabolism 187
Kenneth E. White and Michael J. Econs

26 Gonadal Steroids 194
Stavros C. Manolagas and Maria Schuller Almeida

27 Parathyroid Hormone 205
Thomas J. Gardella, Robert A. Nissenson, and Harald Jüppner

28 Parathyroid Hormone‐Related Protein 212
John J. Wysolmerski and T. John Martin

29 Calcium‐Sensing Receptor 221
Geoffrey N. Hendy

30 Vitamin D Production, Metabolism, Action, and Clinical Requirements 230
Daniel D. Bikle, John S. Adams, and Sylvia Christakos

Section IV Investigation of Metabolic Bone Diseases 241
Section Editors Douglas C. Bauer and Klaus Engelke

31 Techniques of Bone Mass Measurement in Children with Risk Factors for Osteoporosis 243
Nicola J. Crabtree and Leanne M. Ward

32 Standard Techniques of Bone Mass Measurement in Adults 252
E. Michael Lewiecki, Paul D. Miller, and Nelson B. Watts

33 Advanced Techniques of Bone Mass Measurements and Strength in Adults 260
Kyle K. Nishiyama, Enrico Dall’Ara, and Klaus Engelke

34 Magnetic Resonance Imaging of Bone 272
Sharmila Majumdar

35 Trabecular Bone Score 277
Barbara C. Silva and William D. Leslie

36 Reference Point Indentation 287
Adolfo Diez‐Perez and Joshua N. Farr

37 Biochemical Markers of Bone Turnover in Osteoporosis 293
Pawel Szulc, Douglas C. Bauer, and Richard Eastell

38 Scintigraphy and PET in Metabolic Bone Disease 302
Lorenzo Nardo, Paola A. Erba, and Benjamin L. Franc

39 Bone Histomorphometry in Clinical Practice 310
Robert R. Recker and Carolina Aguiar Moreira

40 Diagnosis and Classification of Vertebral Fracture 319
James F. Griffith and Harry K. Genant

41 FRAX Assessment of Fracture Risk 331
John A. Kanis, Eugene V. McCloskey, Nicholas C. Harvey, and William D. Leslie

Section V Genetics of Bone 341
Section Editor Rajesh V. Thakker

42 Introduction to Genetics 343
Paul J. Newey, Michael P. Whyte, and Rajesh V. Thakker

43 Animal Models Genetic Manipulation 351
Karen Lyons

44 Animal Models Allelic Determinants for Bone Mineral Density 359
J. H. Duncan Bassett, Graham R. Williams, and Robert D. Blank

45 Transcriptional Profiling for Genetic Assessment 367
Aimy Sebastian and Gabriela G. Loots

46 Approaches to Genetic Testing 373
Christina Jacobsen, Yiping Shen, and Ingrid A. Holm

47 Human Genome‐Wide Association Studies 378
Douglas P. Kiel, Emma L. Duncan, and Fernando Rivadeneira

48 Translational Genetics of Osteoporosis From Population Association to Individualized Assessment 385
Bich Tran, Jacqueline R. Center, and Tuan V. Nguyen

Section VI Osteoporosis 393
Section Editors Paul D. Miller, Socrates E. Papapoulos, and Michael R. McClung

49 Osteoporosis an Overview 395
Michael R. McClung, Paul D. Miller, and Socrates E. Papapoulos

50 The Epidemiology of Osteoporotic Fractures 398
Nicholas C. Harvey, Elizabeth M. Curtis, Elaine M. Dennison, and Cyrus Cooper

51 Fracture Liaison Service 405
Piet Geusens, John A. Eisman, Andrea Singer, and Joop van den Bergh

52 Sex Steroids and the Pathogenesis of Osteoporosis 412
Matthew T. Drake and Sundeep Khosla

53 Juvenile Osteoporosis 419
Francis H. Glorieux and Craig Munns

54 Transplantation Osteoporosis 424
Peter R. Ebeling

55 Premenopausal Osteoporosis 436
Adi Cohen and Elizabeth Shane

56 Osteoporosis in Men 443
Eric S. Orwoll and Robert A. Adler

57 Bone Stress Injuries 450
Stuart J. Warden and David B. Burr

58 Inflammation‐Induced Bone Loss in the Rheumatic Diseases 459
Ellen M. Gravallese and Steven R. Goldring

59 Glucocorticoid‐Induced Osteoporosis 467
Kenneth Saag and Robert A. Adler

60 Human Immunodeficiency Virus and Bone 474
Michael T. Yin and Todd T. Brown

61 Effects on the Skeleton from Medications Used to Treat Nonskeletal Disorders 482
Nelson B. Watts

62 Diabetes and Fracture Risk 487
Serge Ferrari, Nicola Napoli, and Ann Schwartz

63 Obesity and Skeletal Health 492
Juliet Compston

64 Sarcopenia and Osteoporosis 498
Gustavo Duque and Neil Binkley

65 Management of Osteoporosis in Patients with Chronic Kidney Disease 505
Paul D. Miller

66 Other Secondary Causes of Osteoporosis 510
Neveen A. T. Hamdy and Natasha M. Appelman‐Dijkstra

67 Exercise for Osteoporotic Fracture Prevention and Management 517
Robin M. Daly and Lora Giangregorio

68 Prevention of Falls 526
Heike A. Bischoff‐Ferrari

69 Nutritional Support for Osteoporosis 534
Connie M. Weaver, Bess Dawson‐Hughes, Rene Rizzoli, and Robert P. Heaney

70 Estrogens, Selective Estrogen Receptor Modulators, and Tissue‐Selective Estrogen Complex 541
Tobias J. de Villiers

71 Bisphosphonates for Postmenopausal Osteoporosis 545
Andrea Giusti and Socrates E. Papapoulos

72 Denosumab 553
Aline Granja Costa, E. Michael Lewiecki, and John P. Bilezikian

73 Parathyroid Hormone and Abaloparatide Treatment for Osteoporosis 559
Felicia Cosman and Susan L. Greenspan

74 Combination Anabolic and Antiresorptive Therapy for Osteoporosis 567
Joy N. Tsai and Benjamin Z. Leder

75 Strontium Ranelate and Calcitonin 573
Leonardo Bandeira and E. Michael Lewiecki

76 Adverse Effects of Drugs for Osteoporosis 579
Bo Abrahamsen and Daniel Prieto‐Alhambra

77 Orthopedic Principles of Fracture Management 588
Manoj Ramachandran and David G. Little

78 Adherence to Osteoporosis Therapies 593
Stuart L. Silverman and Deborah T. Gold

79 Cost‐Effectiveness of Osteoporosis Treatment 597
Anna N.A. Tosteson

80 Future Therapies 603
Michael R. McClung

Section VII Metabolic Bone Diseases 611
Section Editors Suzanne M. Jan de Beur and Peter R. Ebeling

81 Approach to Parathyroid Disorders 613
John P. Bilezikian

82 Primary Hyperparathyroidism 619
Shonni J. Silverberg, Francisco Bandeira, Jianmin Liu, Claudio Marcocci, and Marcella D. Walker

83 Familial States of Primary Hyperparathyroidism 629
Andrew Arnold, Sunita K. Agarwal, and Rajesh V. Thakker

84 Non‐Parathyroid Hypercalcemia 639
Mara J. Horwitz

85 Hypocalcemia Definition, Etiology, Pathogenesis, Diagnosis, and Management 646
Anne L. Schafer and Dolores M. Shoback

86 Hypoparathyroidism 654
Tamara Vokes, Mishaela R. Rubin, Karen K. Winer, Michael Mannstadt, Natalie E. Cusano, Harald Jüppner, and John P. Bilezikian

87 Pseudohypoparathyroidism 661
Agnès Linglart, Michael A. Levine, and Harald Jüppner

88 Disorders of Phosphate Homeostasis 674
Mary D. Ruppe and Suzanne M. Jan de Beur

89 Rickets and Osteomalacia 684
Michaël R. Laurent, Nathalie Bravenboer, Natasja M. Van Schoor, Roger Bouillon, John M. Pettifor, and Paul Lips

90 Pathophysiology and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder 695
Mark R. Hanudel, Sharon M. Moe, and Isidro B. Salusky

91 Disorders of Mineral Metabolism in Childhood 705
Thomas O. Carpenter and Nina S. Ma

92 Paget Disease of Bone 713
Julia F. Charles, Ethel S. Siris, and G. David Roodman

93 Epidemiology, Diagnosis, Evaluation, and Treatment of Nephrolithiasis 721
Murray J. Favus and David A. Bushinsky

94 Immobilization and Burns Other Conditions Associated with Osteoporosis 730
William A. Bauman, Christopher Cardozo, and Gordon L. Klein

Section VIII Cancer and Bone 737
Section Editors Theresa Guise and G. David Roodman

95 Mechanisms of Osteolytic and Osteoblastic Skeletal Lesions 739
G. David Roodman and Theresa Guise

96 Clinical and Preclinical Imaging in Osseous Metastatic Disease 743
Siyang Leng and Suzanne Lentzsch

97 Metastatic Tumors and Bone 752
Julie A. Sterling and Rachelle W. Johnson

98 Myeloma Bone Disease and Other Hematological Malignancies 760
Claire M. Edwards and Rebecca Silbermann

99 Osteogenic Osteosarcoma 768
Yangjin Bae, Huan‐Chang Zeng, Linchao Lu, Lisa L. Wang, and Brendan Lee

100 Skeletal Complications of Breast and Prostate Cancer Therapies 775
Catherine Van Poznak and Pamela Taxel

101 Bone Cancer and Pain 781
Denis Clohisy and Lauren M. MacCormick

102 Radiotherapy‐Induced Osteoporosis 788
Laura E. Wright

103 Skeletal Complications of Childhood Cancer 793
Manasa Mantravadi and Linda A. DiMeglio

104 Medical Prevention and Treatment of Bone Metastases 799
Catherine Handforth, Stella D’Oronzo, and Janet Brown

105 Radiotherapy of Skeletal Metastases 809
Srinivas Raman, K. Liang Zeng, Oliver Sartor, Edward Chow, and Øyvind S. Bruland

106 Concepts and Surgical Treatment of Metastatic Bone Disease 816
Kristy Weber and Scott L. Kominsky

Section IX Sclerosing and Dysplastic Bone Diseases 823
Section Editor Michael P. Whyte

107 Sclerosing Bone Disorders 825
Michael P. Whyte

108 Fibrous Dysplasia 839
Michael T. Collins, Alison M. Boyce, and Mara Riminucci

109 The Osteochondrodysplasias 848
Fabiana Csukasi and Deborah Krakow

110 Ischemic and Infiltrative Disorders of Bone 853
Michael P. Whyte

111 Tumoral Calcinosis – Dermatomyositis 861
Nicholas J. Shaw

112 Genetic Disorders of Heterotopic Ossification: Fibrodysplasia Ossificans Progressiva and Progressive Osseous
Heteroplasia 865
Frederick S. Kaplan, Robert J. Pignolo, Mona Al Mukaddam, and Eileen M. Shore

113 Osteogenesis Imperfecta 871
Joan C. Marini

114 Fibrillinopathies Skeletal Manifestations of Marfan Syndrome and Marfan‐Related Conditions 878
Gary S. Gottesman and Michael P. Whyte

115 Hypophosphatasia and Other Enzyme Deficiencies Affecting the Skeleton 886
Michael P. Whyte

Section X Oral and Maxillofacial Biology and Pathology 891
Section Editor Laurie McCauley

116 Craniofacial Morphogenesis 893
Erin Ealba Bumann and Vesa Kaartinen

117 Development and Structure of Teeth and Periodontal Teeth 901
Petros Papagerakis and Thimios Mitsiadis

118 Genetic Craniofacial Disorders Affecting the Dentition 911
Yong‐Hee Patricia Chun, Paul H. Krebsbach, and James P. Simmer

119 Pathology of the Hard Tissues of the Jaws 918
Paul C. Edwards

120 Osteonecrosis of the Jaw 927
Sotirios Tetradis, Laurie McCauley, and Tara Aghaloo

121 Alveolar Bone Homeostasis in Health and Disease 933
Chad M. Novince and Keith L. Kirkwood

122 Oral Manifestations of Metabolic Bone Diseases 941
Erica L. Scheller, Charles Hildebolt, and Roberto Civitelli

123 Dental Implants and Osseous Healing in the Oral Cavity 949
Takashi Matsuura and Junro Yamashita

Section XI Integrative Physiology of the Skeleton 957
Section Editors Mone Zaidi and Clifford J. Rosen

124 Integrative Physiology of the Skeleton 959
Clifford J. Rosen and Mone Zaidi

125 The Hematopoietic Niche and Bone 966
Stavroula Kousteni, Benjamin J. Frisch, Marta Galan‐Diez, and Laura M. Calvi

126 Adipocytes and Bone 974
Clarissa S. Craft, Natalie K. Wee, and Erica L. Scheller

127 The Vasculature and Bone 983
Marie Hélène Lafage‐Proust and Bernard Roche

128 Immunobiology and Bone 992
Roberto Pacifici and M. Neale Weitzmann

129 Cellular Bioenergetics of Bone 1004
Wen‐Chih Lee and Fanxin Long

130 Endocrine Bioenergetics of Bone 1012
Patricia F. Ducy and Gerard Karsenty

131 Central Neuronal Control of Bone Remodeling 1020
Hiroki Ochi, Paul Baldock, and Shu Takeda

132 Peripheral Neuronal Control of Bone Remodeling 1028
Katherine J. Motyl and Mary F. Barbe

133 The Pituitary–Bone Axis in Health and Disease 1037
Mone Zaidi, Tony Yuen, Wahid Abu‐Amer, Peng Liu, Terry F. Davies, Maria I. New, Harry C. Blair, Alberta Zallone, Clifford J. Rosen, and Li Sun

134 Neuropsychiatric Disorders and the Skeleton 1047
Madhusmita Misra and Anne Klibanski

135 Interactions Between Muscle and Bone 1055
Marco Brotto

Index 1063

About the Author

John P. Bilezikian is the Dorothy L. and Daniel H. Silberberg Professor of Medicine and Professor of Pharmacology at the College of Physicians & Surgeons, Columbia University. He is Chief Emeritus of the Division of Endocrinology and Vice-chair of the Department of Medicine for International Research and Education. He is also Director Emeritus of the Metabolic Bone Diseases Program at Columbia University Medical Center.