Genetics of Bone Biology and Skeletal Disease

by Rajesh V. Thakker MD, FRCP, FRS (Editor), Michael P. Whyte MD (Editor), John Eisman MD, PhD, FRACP (Editor), Takashi Igarashi (Editor)

Overview

Genetics of Bone Biology and Skeletal Disease, Third Edition is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid, and related disorders, and vitamin D and renal disorders. Sections cover bone biology and structure, joint and cartilage biology, principles of endocrine regulation, the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasia, rarer bone disorders, and much more.

Product Details

ISBN-13:	9780443136832
Publisher:	Elsevier Science
Publication date:	05/01/2025
Edition description:	3rd ed.
Pages:	900
Product dimensions:	8.50(w) x 10.88(h) x (d)

About the Author

Professor Thakker has been May Professor of Medicine since 1999 and heads a group of scientists that investigate the pathophysiology of human diseases. This team has carried out analyses of more than 15 disorders, with identification of defective genes and functional studies that explain disease phenotypes. This resulted in the elucidation of signaling and regulatory pathways downstream of the calcium-sensing receptor and their physiological relevance; molecular mechanisms of endocrine tumor formation and potential new therapeutic targets; and molecular and cellular aspects of renal tubular physiology.

Professor Thakker’s work has been internationally recognized and received awards including the Louis V. Avioli Founder’s Award from the ASBMR; the Parathyroid Medal from the FRB; the Jack W. Coburn Endowed Lectureship from the ASN; the International Research Prize from the ASBMR; and the Dale Medal from the Society for Endocrinology. Professor Thakker was elected a Fellow of the Royal Society in 2014.

Michael P. Whyte, M.D. is Professor of Medicine, Pediatrics, and Genetics at the Washington University School of Medicine, a staff member of Barnes-Jewish Hospital and St. Louis Children’s Hospital, and Medical-Scientific Director at the Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children in St. Louis, Missouri. Dr. Whyte’s research interests include the cause, outcome, and treatment of heritable disorders of bone and mineral metabolism in children and adults. Included are genetic forms of rickets such as hypophosphatasia and X-linked hypophosphatemia, brittle bone diseases like osteogenesis imperfecta, conditions that cause dense bones such as osteopetrosis, and disorders of accelerated skeletal turnover including juvenile Paget’s disease. Dr. Whyte has authored or coauthored more than 300 scientific papers or book chapters concerning these disorders.

John Eisman AO is Director of Clinical Translation and Advanced Education at Garvan. From 1984 to December 2011, he was Garvan's Director of Osteoporosis and Bone Biology. Professor Eisman was Editor-in-Chief of the Journal of Bone and Mineral Research, is a past member of the Board of the International Bone and Mineral Society and of the Council of the American Society for Bone and Mineral Research. He is a co-founder and past-President of the Australia and New Zealand Bone and Mineral Society. The focus of Professor Eisman’s research is the epidemiology and genetics of osteoporosis, encompassing population, family, and twin studies as well as molecular and cellular mechanisms for gene effects. His major commitment and focus are translating osteoporosis research findings to real improvements in health care delivery to the general community through the education of patients and their doctors.

Takashi Igarashiworks in the Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Mejirodai, Japan.

Table of Contents

PART 1: GENERAL BACKGROUND TO GENETICS AND ‘OMICS 1. Introduction to Genetics of Skeletal and Mineral Metabolic Diseases 2. Genome-Sequencing and Big data analysis 3. Genome-Wide Association Studies 4. Epigenetics 5. Multi-omics approaches in bone research 6. Functional Genomics 7. Organ-on-Chips 8. Mouse Models: Approaches to Generate In Vivo Models for Hereditary Disorders of Mineral and Skeletal 9. Emerging therapeutic approaches (including gene therapy) for Skeletal Diseases 10. Pharmacogenetics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook 11. Drug discovery in the era of cryo-electron microscopy (cryoEM) PART 2: GENERAL BACKGROUND TO BONE BIOLOGY 12. Biology of Bone and Cartilage 13. Overview of Bone Structure and Strength 14. Overview of Joint and Cartilage Biology 15. Osteocyte Biology 16. Skeletal Stem Cells/Bone Marrow Stromal Cells 17. Osteoimmunology 18. Senescence in Bone Disease 19. Chronobiology and clock genes, relevance to musculoskeletal health 20. Mechano-sensing in skeletal biology 21. Hypoxia signalling bone and cartilage 22. Integrating Endocrine and Paracrine Influences on Bone; Lessons from Parathyroid Hormone and Parathyroid 23. Genetics of Bone Fat and Energy Regulation 24. The Cross Talk Between the Central Nervous System, Bone, and Energy Metabolism 25. Fetal Control of Calcium and Phosphate Homeostasis 26. Control of Mineral and Skeletal Homeostasis During Pregnancy and Lactation PART 3: DISORDERS OF BONE AND JOINT 27. Gene discoveries and novel therapies in monogenic low and high bone mass disorders. 28. Osteoporosis 29. Osteogenesis Imperfecta 30. Osteoarthritis: Genetic Studies of Monogenic and Complex Forms 31. Mendelian Disorders of RANKL/OPG/RANK/NF-κB Signalling 32. Skeletal Dysplasias 33. Hypophosphatasia and How Alkaline Phosphatase Promotes Mineralization 34. Sclerosing Bone Dysplasias 35. Melorheostosis 36. Fibrodysplasia (Myositis) Ossificans Progressiva 37. Craniosynostosis 38. Disorders and Mechanisms of Ectopic Calcification 39. Thyroid Hormone in Bone and Joint Disorders PART 4: PARATHYROID AND RELATED DISORDER 40. Hyperparathyroidism 41. Hypoparathyroidism 42. Gsa, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome 43. Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor, its Ligands, and Downstream Effector Molecules 44. Genetically Determined Disorders of Extracellular Calcium (Cao2+) Sensing and Cao2+ Homeostasis 45. Multiple Endocrine Neoplasia Syndromes PART 5: VITAMIN D AND RENAL DISORDERS 46. Genetic Disorders of Vitamin D Synthesis and Action 47. X-linked hypophosphataemia 48. Heritable Renal Phosphate Wasting Disorders 49. Genetics of Hypercalciuria and Kidney Stones

What People are Saying About This

From the Publisher

A fully revised edition of a comprehensive, translational reference on the genetic basis of bone disorders in humans

Editorial Reviews

"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 BookNews.com, 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

From the Publisher