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27 - Skeletal disorders

Published online by Cambridge University Press:  17 August 2009

By
Robert A. Colbert
Edited by
Alan Wright  and
Nicholas Hastie
Alan Wright
Affiliation:
MRC Human Genetics Unit, Edinburgh
Nicholas Hastie
Affiliation:
MRC Human Genetics Unit, Edinburgh
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Summary

Introduction

Recent years have witnessed major advances in our understanding of the genetic basis for many skeletal disorders. In several instances, particularly with the less common Mendelian diseases, the responsible gene has been mapped, mutations identified, and their functional significance determined, contributing significantly to our understanding of the molecular basis for pathogenesis. For more common disorders where susceptibility is complex, a complete picture of the responsible genetic polymorphisms and how they influence pathogenesis has been more difficult to achieve. In this chapter we focus on our current understanding of the genetic basis and pathogenic mechanisms for disorders of bone homeostasis. For readers interested in the genetic basis of developmental disorders of the skeleton, we recommend a recent review (Kornak and Mundlos, 2003).

Bone resorption and bone formation are ongoing processes in both the developing and mature skeleton. Even during growth, where the balance favors bone formation, bone resorption is necessary to remove calcified cartilage prior to the formation of mature bone. In the adult skeleton, there continues to be a dynamic balance between these processes that serves both metabolic and mechanical needs of the individual. Although bone mass continues to increase during childhood, it peaks between the ages of 25 and 35 years, and then begins a steady decline that becomes most prominent after age 50 years when bone formation does not fully compensate bone loss. The delicate balance between bone formation and bone resorption is maintained largely by the coordinated actions of two cell types, osteoblasts and osteoclasts.

Type
Chapter
Information
Genes and Common Diseases
Genetics in Modern Medicine
 , pp. 406 - 426
Publisher: Cambridge University Press
Print publication year: 2007

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