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GENES & DEVELOPMENT 20:2492-2506, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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REVIEW

Genetic regulation of bone mass and susceptibility to osteoporosis

Stuart H. Ralston1,3 and Benoit de Crombrugghe2

1 Rheumatic Diseases Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; 2 Department of Molecular Genetics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risk—such as ultrasound properties of bone, skeletal geometry, and bone turnover—is high, although heritability of fracture is modest. Many different genetic variants of modest effect size are likely to contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Linkage studies in rare Mendelian bone diseases have identified several previously unknown genes that play key roles in regulating bone mass and bone turnover. In many instances, subtle polymorphisms in these genes have also been found to regulate BMD in the general population. Although there has been extensive progress in identifying the genetic variants that regulate susceptibility to osteoporosis, most of the genes and genetic variants that regulate bone mass and susceptibility to osteoporosis remain to be discovered.

[Keywords: Human molecular genetics; linkage; osteoporosis; association studies]

3 Corresponding author.

E-MAIL stuart.ralston{at}ed.ac.uk; FAX 44-131-651-1085.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1449506.


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