What Are the Genetics Behind Osteoporosis?

Osteoporosis is a common degenerative disease causing brittle bones. There are some genetic risk factors for osteoporosis, including changes in genes encoding collagen and estrogen receptors.

Mechanism

• Healthy bones balance their continuous loss and gain of tissue. In osteoporosis, the balance is off. Bone mass decreases; bones become brittle and likely to fracture. The spine and femur (thigh bone) are the most common fracture sites.

Heredity

• Bone density, the most important determinant of bone strength, is a heritable trait, with genetic factors accounting for up to 80 percent of its variance. Daughters of women with osteoporosis have lower bone density and higher risk of fractures. While many genetic factors affect bone turnover, the contribution of each is small, so there is no single gene that causes osteoporosis.

Collagen

• Type I collagen is a major component of healthy bones. Changes in genes for type I collagen, COL1A1 and COL1A2, are associated with osteoporosis. People with the SS or Ss COL1A1 genotype are almost three times more likely to fracture their spine compared to people with the SS genotype.

Estrogen Receptor

• Post-menopausal women have low levels of estrogen and are at the greatest risk for osteoporosis. Women with fewer then 15 repeats of the DNA bases T and A (TA repeats) in a particular region of their ESR1 gene, encoding estrogen receptors, have three times the risk compared to women with higher repeat numbers.

Other Genes

• Changes in the genes IL6, RIL and ITGB3 increase risk for osteoporosis. Such changes might interact with other genes or with environmental factors to affect the risk for osteoporosis.