ArticleJournal of bone and mineral metabolism2011
Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ERα expression and uterine wet weight in ovariectomized rats.
Article in Journal of bone and mineral metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.Pharmacological reports : PR · 2025Review
- Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins.Heliyon · 2025Review
- Simvastatin impairs fracture healing under ischemic conditions.Frontiers in pharmacology · 2025Article
- β-Caryophyllene and Statins in Bone Fracture Healing - A Narrative Review.Orthopedic research and reviews · 2025Review
- Bone-Targeting Nanoparticles of a Dendritic (Aspartic acid)International journal of molecular sciences · 2022Article
- Article
- Molecular targets of statins and their potential side effects: Not all the glitter is gold.European journal of pharmacology · 2022Review
- Remote-controllable bone-targeted delivery of estradiol for the treatment of ovariectomy-induced osteoporosis in rats.Journal of nanobiotechnology · 2021Article
- Improvement of Osseointegration by Ultraviolet and/or Simvastatin Treatment on Titanium Implants with or without Bone Graft Materials.Materials (Basel, Switzerland) · 2021Article
- Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization.Translational oncology · 2020Article
- Atorvastatin promotes bone formation in aged apoEJournal of orthopaedic surgery and research · 2020Article
- Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells.Cancer management and research · 2019Article
- Soy protein improves tibial whole-bone and tissue-level biomechanical properties in ovariectomized and ovary-intact, low-fit female rats.Bone reports · 2018Article
- 8-Prenylgenistein, a prenylated genistein derivative, exerted tissue selective osteoprotective effects in ovariectomized mice.Oncotarget · 2018Article
- Fructus Ligustri Lucidi modulates estrogen receptor expression with no uterotrophic effect in ovariectomized rats.BMC complementary and alternative medicine · 2018Article
- Effect of simvastatin on osteogenesis of the lumbar vertebrae in ovariectomized rats.Experimental and therapeutic medicine · 2016Article
- A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Predictors of mortality subsequent to a fracture in diabetes mellitus patients.Frontiers in endocrinology · 2015Article
- Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats.Journal of bone and mineral metabolism · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported that simvastatin induces estrogen receptor-alpha (ERα) in murine bone marrow stromal cells in vitro. In this study, we investigated the effect of simvastatin on ERα expression in bone and uterus in ovariectomized (OVX) rats and evaluated bone mass, bone strength, and uterine wet weight. Three-month-old Sprague-Dawley female rats received OVX or sham operation. Six weeks later, the rats were treated orally with simvastatin (5 or 10 mg/kg/day), or intraperitoneally with 17-β-estradiol (E(2)) or a combination of simvastatin and E(2) for 6 weeks. Uterine wet weight, bone mineral density (BMD) of lumbar vertebrae, biomechanics of lumbar vertebrae, and induction of ERα expression in the bone and uterus were analyzed. The 6-week simvastatin treatment improved lumbar vertebral BMD and boosted biomechanical performance of the vertebral body compared to the OVX control, suggesting that simvastatin can treat osteoporosis caused by estrogen deficiency. More interestingly, simvastatin could increase ERα expression and synergy with estradiol in bone while antagonizing estradiol in the uterus, along with uterus atrophy and uterine wet weight decreases. In conclusion, these data suggest that simvastatin exert opposing modulatory effects on ERα expression on bone and uterus in ovariectomized rats, inducing ERα expression and synergy with estrogen to perform anabolic effects on the bones while decreasing E2 efficacy and uterine wet weight. This finding may be helpful to explain the mechanism of statin treatment in osteoporosis caused by estrogen deficiency.
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