Genetics of Bone Biology and Skeletal Disease

Edited by

  • Rajesh Thakker, May Professor of Medicine, Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of Oxford; Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford, UK.
  • Michael Whyte, Professor of Medicine, Pediatrics, and Genetics, Washington University in St. Louis School of Medicine; Medical-Scientific Director, Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, USA
  • John Eisman, Director of Bone Research Program, Garvan Institute of Medical Research, Professor of Medicine, University of New South Wales, Australia
  • Takashi Igarashi, Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Mejirodai, Japan; past president of ISN and Japanese Pediatric Association

This book identifies and analyzes the genetic basis of bone disorders in humans and demonstrates the utility of mouse models in furthering the knowledge of mechanisms and evaluations of treatments. The book is aimed at all students of bone biology and genetics, and with this in mind, it includes general introductory chapters on genetics and bone biology and more specific disease-orientated chapters, which comprehensively summarize the clinical, genetic, molecular genetic, animal model, functional and molecular pathology, diagnostic, counselling and treatment aspects of each disorder.
View full description


Primary: Academic, medical, and pharmaceutical researchers in bone biology, clinical genetics, rheumatology, endocrinology, osteology; Secondary: Clinicians who threat metabolic bone diseases and musculoskeletal disorders (endocrinologists, rheumatologists, osteologists) and offer genetic counseling.


Book information

  • Published: November 2012
  • ISBN: 978-0-12-387829-8


"With the aims of identifying and analyzing the genetic basis of bone disorders in humans and of demonstrating the utility of mouse models, this volume presents 36 chapters that are inter-related, yet self-contained, with some overlap. Coverage is comprehensive."--Reference and Research, April 2013
"The last ten years have witnessed an explosion in genomics and through its application to bone biology, the identification of novel potential targets for therapeutic interventions in bone diseases, such as osteoporosis. This textbook is therefore very timely and integrates a review of bone biology with the genetics of bone and joint disorders, parathyroid and related disorders, and vitamin D and renal diseases.
The section on osteoporosis genes identified by genome-wide association studies is particularly useful and effectively summarises a subset of the at least 56 loci that have shown a robust association with BMD at genome-wide significant level and have been replicated. Although these genes explain only about 4% of the variation in BMD and cannot be used to improve fracture risk prediction, they have pinpointed many factors in critical molecular pathways in bone that provide promising candidates for novel therapeutic interventions.
The section on genetic disorders of vitamin D synthesis and action elegantly shows how the study of affected children with 1a-hydroxylase deficiency and hereditary vitamin D resistant rickets continues to provide a more complete understanding of the biological role of 1,25(OH)2D in vivo.
In conclusion, if you want to find one place to "bone up" on the genetics of skeletal disease, this is the book for you!"--Professor Peter R. Ebeling MD FRACP,
The University of Melbourne, Melbourne, Australia
"This book brings together the world’s most expert bone biologists, clinicians and geneticists to provide a cutting-edge review of bone from a genetic perspective. It provides a well-written account of bone biology, genetic techniques in general, and their application to bone biology and therapeutics, both of common and esoteric conditions. It provides an accessible and comprehensive treatment of one of the most rapidly advancing areas of bone research today."--Prof Ian Reid, BSc, MBChB, MD, FRACP, FRSNZ, FRCP, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

Table of Contents

Part I: General Background to Bone Biology

  1. Biology of Bone and Cartilage
  2. Brendan Boyce, Michael Zuscik, Lianping Xing

  3. Overview of Bone Structure and Strength
  4. Mary L. Bouxsein

  5. Overview of Joint and Cartilage Biology
  6. Frank Luyten and Rik JU Lories

  7. Integrating Endocrine and Paracrine Influences on Bone: Lessons from Parathyroid Hormone and Parathyroid Hormone-related Protein
  8. T. John Martin and Natalie A. Sims

  9. Energy Homeostasis and Neuronal Regulation of Bone Remodeling
  10. Gerard Karsenty, Mathieu Ferron and Franck Oury

  11. Neuropeptide Y and Bone Regulation
  12. Paul A. Baldock

    Part II: General Background to Genetics

  13. Genome-wide Association Studies
  14. Matthew Brown and Emma L. Duncan

  15. Genomic Profiling in Bone
  16. Gabriela G. Loots and Bryan D. Hudson

  17. Copy Number Variation
  18. Hong-Wen Deng, Tie-Lin Yang, Yan Guo and Christopher J. Papasian

  19. Prospects of Gene Therapy
  20. Brendan Lee, Merry ZC Ruan and Kilian Guse

  21. Pharmacogentics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook
  22. Tuan V. Nguyen and John A. Eisman

  23. Genetic Testing & Counselling
  24. Ingrid A. Holm, Christina M. Jacobsen, Yiping Shen and Stephanie J. Brewster

  25. Mouse models: Approaches to Generating in vivo Models for Hereditary Disorders of Mineral and Skeletal Homeostasis
  26. Sian E. Piret and Rajesh V. Thakker

  27. Fetal Control of Calcium and Phosphate Homeostasis - Lessons from Mouse Models
  28. Christopher S. Kovacs

  29. Control of Skeletal Homeostasis during Pregnancy and Lactation - Lessons from Physiological Models
  30. Christopher S. Kovacs

    Part III: Disorders of Bone and Joint

  31. Osteogenesis Imperfecta
  32. Joan Marini and M. Helen Rajpar

  33. Osteoporosis Genes Identified by Genome-wide Association Studies
  34. Andre Uitterlinden and Fernando Rivadenerira

  35. Osteoarthritis - Genetic Studies of Monogenic and Complex Forms
  36. Ana M. Valdes

  37. Paget’s Disease
  38. Stuart H. Ralston and Omar M.E. Albagha

  39. Heritable Disorders of RANKL, OPG, RANK and NF-KB Signalling
  40. Michael Whyte

  41. Skeletal Dysplasias
  42. William G. Cole

  43. Hypophosphatasia
  44. Michael P. Whyte

  45. Sclerosing Bone Disorders
  46. Bram Perdu and Wim Van Hul

  47. Fibrodysplasia (Myositis) Ossificans Progressiva
  48. Andria L. Culbert, Salin A. Chakkalakal, Michael R. Convente, Vitali Y. Lounev, Frederick S. Kaplan and Eileen M. Shore

    Part IV: Parathyroid and Related Disorders

  49. Hyperparathyroidism
  50. Andrew Arnold and Jessica Costa-Guda

  51. Hypoparathyroidism
  52. Rajesh V. Thakker

  53. Gsa, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune-Albright Syndrome
  54. Lee S. Weinstein, Allen M. Spiegel and Michael Collins

  55. Genetic disorders affecting PTH/PTHrP receptor function
  56. Harald Jueppner and Caroline Silve

  57. Genetically Determined Disorders of the Calcium-Sensing Receptor
  58. Edward M. Brown and Ogo I. Egbuna

  59. Multiple Endocrine Neoplasia Type 1 (MEN1)
  60. Rajesh V. Thakker

  61. Multiple Endocrine Neoplasia Type 2 (MEN2)
  62. Bruce Robinson, Rory Clifton-Bligh and Matti Gild

    Part V: Vitamin D and Renal Disorders

  63. Heritable Renal Phosphate Wasting Disorders
  64. Marc K. Drezner

  65. Genetic Disorders of Vitamin D Synthesis and Action
  66. David Feldman, Peter Malloy and Walter L. Miller

  67. Renal Fanconi Syndrome, Dent's Disease and Bartter's Syndrome
  68. Olivier Devuyst and Takashi Igarashi

  69. Inherited Magnesium Disorders
  70. Scott J. Schurman, Dhruval Patel, Anil Singh and Steven J. Scheinman

  71. Genetic Hypercalciuria: A Major Risk Factor in Kidney Stones

David Bushinsky and Orson W. Moe