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

Bone. 2013 Mar;53(1):42-50. doi: 10.1016/j.bone.2012.11.011. Epub 2012 Nov 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Estrogens / pharmacology*
  • Estrogens / therapeutic use
  • Humans
  • Osteoporosis / drug therapy*
  • Osteoporosis / prevention & control*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Sterols / pharmacology*
  • Sterols / therapeutic use

Substances

  • Estrogens
  • Selective Estrogen Receptor Modulators
  • Sterols