title: Genetic regulation of bone mass and susceptibility to osteoporosis.
abstract: 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.
authors.affiliation: Rheumatic Diseases Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. stuart.ralston@ed.ac.uk
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008954:Models, Biological; D010024:Osteoporosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002118:Calcium