The molecular mechanisms underlying the pharmacological actions of estrogens, SERMs and oxysterols: implications for the treatment and prevention of osteoporosis.

Journal Article (Journal Article;Review)

Estrogen therapy and hormone therapy are effective options for the prevention and treatment of osteoporosis, although because of their significant side effect profile, long term use for these applications is not recommended. Whereas SERMs (Selective Estrogen Receptor Modulators) exhibit a more favorable side effect profile, the currently available medicines in this class are substantially less effective in bone than classical estrogens. However, the results of substantial efforts that have gone into defining the mechanisms that underlie the pharmacology of estrogens, antiestrogens and SERMs have informed the development of the next generation of SERMs and have led to the development of TSECs (Tissue Selective Estrogen Complexes), a new class of ER-modulator. Further, the recent determination that the oxysterol 27-hydroxycholesterol functions as an endogenous SERM has highlighted an unexpected link between hypercholesterolemia and bone biology and must be considered in any discussions of ER-pharmacology. This review considers the most recent progress in our understanding of ER pharmacology and how this has and will be translated into new medicines for the treatment and prevention of osteoporosis.

Full Text

Duke Authors

Cited Authors

  • Nelson, ER; Wardell, SE; McDonnell, DP

Published Date

  • March 2013

Published In

Volume / Issue

  • 53 / 1

Start / End Page

  • 42 - 50

PubMed ID

  • 23168292

Pubmed Central ID

  • PMC3552054

Electronic International Standard Serial Number (EISSN)

  • 1873-2763

Digital Object Identifier (DOI)

  • 10.1016/j.bone.2012.11.011


  • eng

Conference Location

  • United States