ArticleAmerican journal of physiology. Endocrinology and metabolism2016
SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice.
Article in American journal of physiology. Endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Sex steroids and autoimmune rheumatic diseases: state of the art.Nature reviews. Rheumatology · 2020Pooled it
- Long-term effects of ospemifene on densitometric and bone metabolism biomarkers in postmenopausal women reporting Vulvar and Vaginal Atrophy (VVA).BMC women's health · 2026Article
- Bazedoxifene and Beyond: Identifying This SERM's Targets and Deciphering Its Molecular Mechanisms.Advances in pharmacological and pharmaceutical sciences · 2026Review
- Insights and implications of sexual dimorphism in osteoporosis.Bone research · 2024Review
- A tissue-specific role of membrane-initiated ERα signaling for the effects of SERMs.The Journal of endocrinology · 2022Article
- Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications.International journal of molecular sciences · 2021Review
- Tissue selective effects of bazedoxifene on the musculoskeletal system in female mice.The Journal of endocrinology · 2021Article
- Estrogen Regulates the Satellite Cell Compartment in Females.Cell reports · 2019Article
- Tissue selective estrogen complex (TSEC): a review.Menopause (New York, N.Y.) · 2018Review
- Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018Article
- Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2017Article
- Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-1(0)) 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-1(0) 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.