SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofo...

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Main Authors:	Börjesson, Anna E., Farman, Helen H., Movérare-Skrtic, Sofia, Engdahl, Cecilia, Antal, Maria Cristina, Koskela, Antti, Tuukkanen, Juha, Carlsten, Hans, Krust, Andrée, Chambon, Pierre, Sjögren, Klara, Lagerquist, Marie K., Windahl, Sara H., Ohlsson, Claes
Format:	Online
Language:	English
Published:	American Physiological Society 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935145/

id	pubmed-4935145
recordtype	oai_dc
spelling	pubmed-49351452016-07-15 SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice Börjesson, Anna E. Farman, Helen H. Movérare-Skrtic, Sofia Engdahl, Cecilia Antal, Maria Cristina Koskela, Antti Tuukkanen, Juha Carlsten, Hans Krust, Andrée Chambon, Pierre Sjögren, Klara Lagerquist, Marie K. Windahl, Sara H. Ohlsson, Claes Articles The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. American Physiological Society 2016-04-05 2016-06-01 /pmc/articles/PMC4935145/ /pubmed/27048997 http://dx.doi.org/10.1152/ajpendo.00488.2015 Text en Copyright © 2016 the American Physiological Society http://creativecommons.org/licenses/by/3.0/deed.en_US Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : © the American Physiological Society.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Börjesson, Anna E. Farman, Helen H. Movérare-Skrtic, Sofia Engdahl, Cecilia Antal, Maria Cristina Koskela, Antti Tuukkanen, Juha Carlsten, Hans Krust, Andrée Chambon, Pierre Sjögren, Klara Lagerquist, Marie K. Windahl, Sara H. Ohlsson, Claes
spellingShingle	Börjesson, Anna E. Farman, Helen H. Movérare-Skrtic, Sofia Engdahl, Cecilia Antal, Maria Cristina Koskela, Antti Tuukkanen, Juha Carlsten, Hans Krust, Andrée Chambon, Pierre Sjögren, Klara Lagerquist, Marie K. Windahl, Sara H. Ohlsson, Claes SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
author_facet	Börjesson, Anna E. Farman, Helen H. Movérare-Skrtic, Sofia Engdahl, Cecilia Antal, Maria Cristina Koskela, Antti Tuukkanen, Juha Carlsten, Hans Krust, Andrée Chambon, Pierre Sjögren, Klara Lagerquist, Marie K. Windahl, Sara H. Ohlsson, Claes
author_sort	Börjesson, Anna E.
title	SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
title_short	SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
title_full	SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
title_fullStr	SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
title_full_unstemmed	SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice
title_sort	serms have substance-specific effects on bone, and these effects are mediated via erαaf-1 in female mice
description	The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis.
publisher	American Physiological Society
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935145/
_version_	1613605155899441152

SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

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