Estrogen receptor gene polymorphisms and the genetics of osteoporosis: A HuGE review

Luigi Gennari, D. Merlotti, V. De Paola, A. Calabrò, L. Becherini, G. Martini, R. Nuti

Research output: Contribution to journalArticlepeer-review


Osteoporosis (OMIM166710) is a common skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with increased susceptibility to fracture. Osteoporosis has a complex etiology and is considered a multifactorial polygenic disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. Estrogens are known to play an important role in regulating bone homeostasis and preventing postmenopausal bone loss. They act through binding to two different estrogen receptors (ERs), ERα (OMIM133430) and ERβ (OMIM601663), which are members of the nuclear receptor superfamily of ligand-activated transcription factors. Different polymorphisms have been described in both the ERα and ERβ genes. Although a large number of association studies have been performed, the individual contribution of these polymorphisms to the pathogenesis of osteoporosis remains to be universally confirmed. Moreover, an important aim in future work will be to define their functional molecular consequences and their interaction with the environment in the causation of the osteoporotic phenotype. A further promising application of these polymorphisms comes from their pharmacogenomic implications, with the possibility of providing better guidance for therapeutic regimens, such as estrogen replacement therapy and selective ER modulators. At the moment, no recommendations for population-based screening can be made.

Original languageEnglish
Pages (from-to)307-320
Number of pages14
JournalAmerican Journal of Epidemiology
Issue number4
Publication statusPublished - Feb 15 2005


  • Epidemiology
  • Estrogen receptor alpha
  • Estrogen receptor beta
  • Genetics
  • Genome, human
  • Osteoporosis
  • Polymorphism, genetic

ASJC Scopus subject areas

  • Epidemiology


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