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

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.

Product Details

ISBN-13:	9780443136832
Publisher:	Elsevier Science
Publication date:	12/01/2025
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 I: General Background to Bone Biology
1. Biology of Bone and Cartilage
Brendan Boyce, Michael Zuscik, Lianping Xing
2. Overview of Bone Structure and Strength
Mary L. Bouxsein
3. Overview of Joint and Cartilage Biology
Frank Luyten and Rik JU Lories
4. Integrating Endocrine and Paracrine Influences on Bone: Lessons from Parathyroid Hormone and Parathyroid Hormone-related Protein
T. John Martin and Natalie A. Sims
5. Energy Homeostasis and Neuronal Regulation of Bone Remodeling
Gerard Karsenty, Mathieu Ferron and Franck Oury
6. Neuropeptide Y and Bone Regulation
Paul A. Baldock

Part II: General Background to Genetics
7. Genome-wide Association Studies
Matthew Brown and Emma L. Duncan
8. Genomic Profiling in Bone
Gabriela G. Loots and Bryan D. Hudson
9. Copy Number Variation
Hong-Wen Deng, Tie-Lin Yang, Yan Guo and Christopher J. Papasian
10. Prospects of Gene Therapy
Brendan Lee, Merry ZC Ruan and Kilian Guse
11. Pharmacogentics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook
Tuan V. Nguyen and John A. Eisman
12. Genetic Testing & Counselling
Ingrid A. Holm, Christina M. Jacobsen, Yiping Shen and Stephanie J. Brewster
13. Mouse models: Approaches to Generating in vivo Models for Hereditary Disorders of Mineral and Skeletal Homeostasis
Sian E. Piret and Rajesh V. Thakker
14. Fetal Control of Calcium and Phosphate Homeostasis – Lessons from Mouse Models
Christopher S. Kovacs
15. Control of Skeletal Homeostasis during Pregnancy and Lactation – Lessons from Physiological Models
Christopher S. Kovacs

Part III: Disorders of Bone and Joint
16. Osteogenesis Imperfecta
Joan Marini and M. Helen Rajpar
17. Osteoporosis Genes Identified by Genome-wide Association Studies
Andre Uitterlinden and Fernando Rivadenerira
18. Osteoarthritis – Genetic Studies of Monogenic and Complex Forms
Ana M. Valdes
19. Paget’s Disease
Stuart H. Ralston and Omar M.E. Albagha
20. Heritable Disorders of RANKL, OPG, RANK and NF-KB Signalling
Michael Whyte
21. Skeletal Dysplasias
William G. Cole
22. Hypophosphatasia
Michael P. Whyte
23. Sclerosing Bone Disorders
Bram Perdu and Wim Van Hul
24. Fibrodysplasia (Myositis) Ossificans Progressiva
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
25. Hyperparathyroidism
Andrew Arnold and Jessica Costa-Guda
26. Hypoparathyroidism
Rajesh V. Thakker
27. Gsa, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune-Albright Syndrome
Lee S. Weinstein, Allen M. Spiegel and Michael Collins
28. Genetic disorders affecting PTH/PTHrP receptor function
Harald Jueppner and Caroline Silve
29. Genetically Determined Disorders of the Calcium-Sensing Receptor
Edward M. Brown and Ogo I. Egbuna
30. Multiple Endocrine Neoplasia Type 1 (MEN1)
Rajesh V. Thakker
31. Multiple Endocrine Neoplasia Type 2 (MEN2)
Bruce Robinson, Rory Clifton-Bligh and Matti Gild

Part V: Vitamin D and Renal Disorders
32. Heritable Renal Phosphate Wasting Disorders
Marc K. Drezner
33. Genetic Disorders of Vitamin D Synthesis and Action
David Feldman, Peter Malloy and Walter L. Miller
34. Renal Fanconi Syndrome, Dent's Disease and Bartter's Syndrome
Olivier Devuyst and Takashi Igarashi
35. Inherited Magnesium Disorders
Scott J. Schurman, Dhruval Patel, Anil Singh and Steven J. Scheinman
36. Genetic Hypercalciuria: A Major Risk Factor in Kidney Stones
David Bushinsky and Orson W. Moe

What People are Saying About This

From the Publisher

This comprehensive, translational reference for students of bone biology and genetics covers 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