Genetic polymorphisms of estrogen receptor-α: Possible implications for targeted osteoporosis therapy

Abstract

Genetic factors play an important role in the determination of bone mass and osteoporosis. A number of candidate genes have been implicated in osteoporosis, including genes encoding type 1 collagen, vitamin D receptor, estrogen receptor-α (ERα), and others. A number of association studies have been performed with single nucleotide polymorphisms in the ERα gene to assess their relation with bone mineral density in pre- and postmenopausal women, as well as the rate of bone loss after menopause and skeletal response to estrogen administration. The polymorphisms studied thus far mostly involved intronic polymorphisms in intron 1. Other less frequently studied polymorphisms include those in exons 1, 4, and 8. Although most studies demonstrated associations with various bone-related parameters, the results are still disputed. Assessing genetic factors including ERα polymorphisms, if their significances are confirmed, can be helpful in targeting preventive measures to individuals with higher risk of developing osteoporosis and render the preventive effort more cost-effective. Moreover, pharmacogenetically, it may help identify postmenopausal women who tend to have better skeletal responses after estrogen replacement. It is not known, however, if patients who possess favorable polymorphisms in terms of skeletal responsiveness will also have an undesirably higher risk of adverse effects. This issue needs to be further investigated before clinical decisions based on the balance between benefits and risks can be made.