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Genetics of Osteoporosis

written by: Finn Orfano • edited by: Paul Arnold • updated: 11/21/2009

Osteoporosis is a disease of decreased bone density. Bones can become fragile and thin, increasing the likelihood of fractures and breaks. The health consequences can be devastating. Genetics is one of the many factors that plays a significant role in the development of the condition.

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    A Person with Osteoporosis

    Detecting association between osteoporosis and genetics is difficult because of the nature of the disease. Genes that make proteins in the cells have been linked to the development of osteoporosis. The genetics of osteoporosis deals with mutations in genes that control bone mass. There are at least 30 genes associated with the development of osteoporosis. Although research in this field has been slow to get off the ground, it has become much more intense in recent years. However, it is known that a person with a family history of fractures or osteoporosis are at an increased risk.

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    A genetic basis

    A much clearer picture of how genes affect bones is being revealed and several candidates have been singled out by researchers.

    It is well known that in women a deficiency of the hormone estrogen leads to bone mass reduction, and there's a correlation between a mutation in the estrogen receptor gene and decreased bone mineral density (Frederic 1997).

    There is an association between muscle strength and the vitamin D receptor (VDR) genotypes in men. Men 60-80 years of age with a recessive form of the VDR gene have greater muscle strength than men with the dominant gene. There is also a correlation between the VDR gene and the bone mineral density protein gene (BMD) for increasing the likelihood of osteoporotic fractures (Bischoff 2000). However, studies are still being done to figure out if there are any effects on the bone mineral density due to genotype of the VDR gene.

    There is a strong association between the COL1A1 gene and BMD gene. Greek postmenopausal women with a recessive genotype have been linked to an inherited pathological component of bone mineral density. Mutations in the coding region of the COLIA1 and COLIA2 genes, important for bone development, can lead to abnormal bone strength and density (Georgiadis 2000).

    Recent research has shown that there are two genes, located on chromosome 9 and 11, that have an important role for an increased risk of osteoporosis and osteoporotic fracture. The gene on chromosome 8 was found near the osteoprotegerin gene (TNFRSF11B) and the one on chromosome 11 was found within the gene that has been associated with decreased bone mineral density (Richards 2008).

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    Heritability

    Studies from family histories, twin studies, and molecular genetics have indicated that bone mass is heritable. Some estimate the heritability factor to be as much as 80%. Whilst there are many non-genetic factors that increase the risk of osteoporosis, such as lack of calcium in the diet and early menopause, it is clear that genetics also plays a significant role.

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    References

    Bischoff HA, Dick W, Geusens P, et al. Influence of VDR polymorphism on muscle strength in men. Osteoporos Int. 2000;11(suppl 2):S89.

    Frederic A. Spangler, Janet L. Padgett & Wilma S. Ek. The Genetic Component of Osteoporosis. ProQuest 1997. http://www.csa.com/discoveryguides/archives/osteo.php

    Georgiadis EA, Billi C, Georgiadis AE, Florentin L. Evidence that COL1A1 genotype but not vitamin D receptor genotype (VDR) may contribute to the heritability of bone mineral density in postmenopausal women (PMW) in Greece. Osteoporos Int. 2000;11(suppl 2):S147.

    Richards JB, Rivadeneira F, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 2008;37(9623):1505-1512