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Menopause (New York, N.Y.) Jan 2014
Topics: Bone Density Conservation Agents; Female; Humans; Osteoporosis, Postmenopausal; Postmenopause; Raloxifene Hydrochloride; Stroke
PubMed: 24326283
DOI: 10.1097/GME.0000000000000158 -
International Journal of Biological... Aug 2020This study intended to design novel nanofibrillated cellulose/cyclodextrin-based 3D scaffolds loaded with raloxifene hydrochloride for bone regeneration. The scaffolds...
This study intended to design novel nanofibrillated cellulose/cyclodextrin-based 3D scaffolds loaded with raloxifene hydrochloride for bone regeneration. The scaffolds were prepared using two different types of cyclodextrins namely; beta-cyclodextrin and methyl-beta-cyclodextrin. The prepared scaffolds were evaluated by characterizing their porosity, compressive strength, in-vitro drug release, FT-IR and XRD as well as their morphological properties using SEM. Results presented that the prepared scaffolds were highly porous, additionally, the scaffold containing drug/beta-cyclodextrin kneaded complex (SC5) showed the most controlled drug release pattern with the least burst effect and reached almost complete release at 480 h. The in-vitro cytocompatibility and regenerative effect of the chosen scaffold (SC5) was assessed using Saos-2 cell line. Results proved that SC5 was biocompatible. Moreover, it enhanced the cell adhesion, alkaline phosphatase enzyme expression and calcium ion deposition which are essential factors for bone mineralization. The obtained observations presented a novel, safe and propitious approach for bone engineering.
Topics: Biomarkers; Bone Density Conservation Agents; Bone Regeneration; Cell Differentiation; Cell Survival; Cellulose; Cyclodextrins; Humans; Porosity; Raloxifene Hydrochloride; Spectroscopy, Fourier Transform Infrared; Tissue Engineering; Tissue Scaffolds; X-Ray Diffraction
PubMed: 32289405
DOI: 10.1016/j.ijbiomac.2020.04.019 -
EBioMedicine Dec 2023Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets...
BACKGROUND
Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets using Mendelian randomization (MR) and then validate the candidate drugs using population-based analyses.
METHODS
We identified genetic instruments for 1406 actionable targets of approved non-oncological drugs based on gene expression, DNA methylation, and protein expression quantitative trait loci (eQTL, mQTL, and pQTL, respectively). Genome-wide association study (GWAS) summary statistics were obtained from the Breast Cancer Association Consortium (122,977 cases, 105,974 controls). We further conducted a nested case-control study using data retrieved from Swedish registers to validate the candidate drugs that were identified from MR analyses.
FINDINGS
We identified six significant MR associations with gene expression levels (TUBB, MDM2, CSK, ULK3, MC1R and KCNN4) and two significant associations with gene methylation levels across 21 CpG islands (RPS23 and MAPT). Results from the nested case-control study showed that the use of raloxifene (targeting MAPT) was associated with 35% reduced breast cancer risk (odds ratio, OR, 0.65; 95% confidence interval, CI, 0.51-0.83). However, usage of estradiol, tolterodine, and nitrofurantoin (also targeting MAPT) was associated with increased breast cancer risk, with adjusted ORs and 95% CI of 1.10 (1.07-1.13), 1.16 (1.09-1.24), and 1.09 (1.05-1.13), respectively. The effect of raloxifene and nitrofurantoin lost significance in further validation analyses using active-comparator and new-user design.
INTERPRETATION
This large-scale MR analysis, combined with population-based validation, identified eight druggable target genes for breast cancer and suggested that raloxifene is an effective chemoprevention against breast cancer.
FUNDING
Swedish Research Council, Cancerfonden, Crafoordska Stiftelsen, Allmänna Sjukhusets i Malmö Stiftelsen för bekämpande av cancer, 111 Project and MAS cancer.
Topics: Humans; Female; Breast Neoplasms; Case-Control Studies; Genome-Wide Association Study; Mendelian Randomization Analysis; Nitrofurantoin; Raloxifene Hydrochloride
PubMed: 38251461
DOI: 10.1016/j.ebiom.2023.104859 -
European Journal of Orthodontics Sep 2020Orthodontic relapse is a physiologic process that involves remodelling of the alveolar bone and principle periodontal ligament fibres. Raloxifene is an Food and Drug...
BACKGROUND AND OBJECTIVES
Orthodontic relapse is a physiologic process that involves remodelling of the alveolar bone and principle periodontal ligament fibres. Raloxifene is an Food and Drug Administration (FDA)-approved selective oestrogen receptor modulator that inhibits systemic bone loss. In our study, we examined the effects of Raloxifene on alveolar bone modelling and orthodontic relapse in a rodent model.
MATERIALS AND METHODS
The efficacy of raloxifene was evaluated in 15-week-old male Wistar rats, 8 in each group (Control, Raloxifene, Raloxifene + 7-day relapse, Raloxifene + 14-day relapse) for a total of 42 days. All animals had 14 days of orthodontic tooth movement with a closed nickel-titanium coil spring tied from incisors to right first molar applying 5-8 gm of force. On the day of appliance removal, impression was taken with silicon material and the distance between first molar and second molar was filled with light-cured adhesive resin cement for retention phase. Raloxifene Retention, Raloxifene Retention + 7D, Raloxifene Retention + 14D groups received 14 daily doses of raloxifene (2.0 mg/kg/day) subcutaneously after orthodontic tooth movement during retention. After 14 days of retention, the retainer was removed and right first molar was allowed to relapse for a period of 14 days. Raloxifene injection continued for the Raloxifene + 14-day relapse group during relapse phase too. Control group received saline injections during retention. Animals were euthanized by CO2 inhalation. The outcome measure included percentage of relapse, bone volume fraction, tissue density, and histology analysis using tartrate-resistant acid phosphatase staining and determining receptor activator of nuclear factor-кB-ligand (RANKL) and osteoprotegerin expression.
RESULTS
Raloxifene Retention + 14D group had significantly less (P < 0.05) orthodontic relapse when compared with other groups. There was a significant increase (P < 0.05) in bone volume fraction and tissue density in the Raloxifene Retention + 14D group when compared with other groups. Similarly, there was significant decrease in number of osteoclasts and RANKL expression in Raloxifene Retention + 14D group when compared with Raloxifene Retention + 7D group (P < 0.05).
CONCLUSION
Raloxifene could decrease post-orthodontic treatment relapse by decreasing bone resorption and indirectly enhancing bone formation.
Topics: Animals; Bone Remodeling; Male; Molar; Osteoclasts; Raloxifene Hydrochloride; Rats; Rats, Wistar; Recurrence; Tooth Movement Techniques
PubMed: 32065225
DOI: 10.1093/ejo/cjaa008 -
Integrative Cancer Therapies Sep 2016
Topics: Breast Neoplasms; Estrogen Antagonists; Female; Humans; Raloxifene Hydrochloride; Substance Withdrawal Syndrome; Translational Research, Biomedical
PubMed: 27271771
DOI: 10.1177/1534735416651329 -
Menopause (New York, N.Y.) 2009In this article, we provide an interdisciplinary concise review of the effects of raloxifene on breast, bone, and reproductive organs, as well as the adverse events that... (Review)
Review
OBJECTIVE AND METHODS
In this article, we provide an interdisciplinary concise review of the effects of raloxifene on breast, bone, and reproductive organs, as well as the adverse events that may be associated with its use.
RESULTS
Raloxifene has been shown to prevent osteoporosis in postmenopausal women (PMW) with low bone mass and prevent vertebral fractures in those with osteoporosis/low bone mass; it has not been shown to reduce the risk of nonvertebral fractures. Raloxifene reduces the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. The risk of venous thromboembolism has been consistently shown to be increased with raloxifene, so it should not be used in women at high risk of venous thromboembolism. Although raloxifene does not increase, nor decrease, the risk of coronary or stroke events overall, in the raloxifene trial of PMW at increased risk of coronary events, the incidence of fatal stroke was higher in women assigned raloxifene versus placebo.
CONCLUSIONS
Based on its approved indications, it is appropriate to prescribe raloxifene to prevent or treat osteoporosis, as well as to reduce the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. Women at increased risk of both fracture and invasive breast cancer are those most likely to receive a dual benefit with raloxifene. Decision making must involve the incorporation of the woman's personal feelings about the risks and benefits of raloxifene therapy, balanced with her interest in reducing risk of fractures and breast cancer through pharmacological intervention.
Topics: Breast Neoplasms; Female; Fractures, Bone; Humans; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators; Treatment Outcome
PubMed: 19092711
DOI: 10.1097/gme.0b013e3181883dae -
Clinical Interventions in Aging 2008Raloxifene is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raloxifene... (Review)
Review
Raloxifene is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raloxifene decreases the incidence of vertebral fractures by 30%-50% in postmenopausal women with osteoporosis but has not been shown to decrease the incidence of hip fractures or other non-vertebral fractures. At the present time, estrogen-replacement therapy and bisphosphonate treatment are the only medical treatments that are proven to prevent hip fractures with the exception of vitamin D and calcium replacement, which has been shown to prevent hip fractures in elderly individuals and nursing home residents. Raloxifene has been shown to have additive effects on bone turnover and bone mineral density (BMD) when used along with alendronate and teriparatide. Raloxifene could have a role in renal failure as it has been shown to increase BMD of the vertebra over 1 year of therapy. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. The increased incidence of venous thromboembolism is the main concern of raloxifene therapy and previous history of venous thromboembolism is a contraindication for use of raloxifene. Raloxifene has a role in treatment of vertebral osteoporosis in older women. The decision to use raloxifene should be based on evaluation of fracture risk and on potential other benefits than fracture reduction along with consideration of side effects.
Topics: Bone and Bones; Breast Neoplasms; Cardiovascular System; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators
PubMed: 18488877
DOI: 10.2147/cia.s224 -
Expert Review of Anticancer Therapy Aug 2004Raloxifene (Evista, Eli Lilly), a selective estrogen receptor modulator (SERM) and ligand for the estrogen receptor (ER), competes with endogenous estrogen for ER... (Review)
Review
Raloxifene (Evista, Eli Lilly), a selective estrogen receptor modulator (SERM) and ligand for the estrogen receptor (ER), competes with endogenous estrogen for ER binding. Raloxifene is approved for the prevention and treatment of osteoporosis, and shows promise as a breast cancer prevention drug. Raloxifene may be a preferred agent over tamoxifen due to its side-effect profile; in particular, it does not stimulate the endometrium and is not associated with endometrial cancer. The mechanisms for the differential tissue effects of raloxifene compared with other SERMs are not completely understood; the roles of ERalpha and -beta, classic and alternative signaling pathways, and drug conformation are discussed in this review. The utility of raloxifene will depend on the outcome of trials that are now underway, as well as acceptance by high-risk women and their healthcare practitioners.
Topics: Breast Neoplasms; Chemoprevention; Clinical Trials as Topic; Estrogen Antagonists; Female; Humans; Osteoporosis; Raloxifene Hydrochloride; Risk Factors; Signal Transduction
PubMed: 15270657
DOI: 10.1586/14737140.4.4.523 -
Expert Opinion on Pharmacotherapy May 2013Osteoporosis is a common disease characterized by the occurrence of fragility fractures. Major osteoporotic fractures are associated with decreased quality of life and... (Review)
Review
INTRODUCTION
Osteoporosis is a common disease characterized by the occurrence of fragility fractures. Major osteoporotic fractures are associated with decreased quality of life and high costs.
AREAS COVERED
This review summarizes clinical data on raloxifene (RLX), a second generation selective estrogen-receptor modulator (SERM), currently approved for the treatment of postmenopausal osteoporosis. RLX has estrogen effects on bone and lipid profile, whereas it has anti-estrogen effects on uterus and breast cells. Its main side effects are hot flushes and venous thromboembolism. Literature searches were conducted to retrieve articles reporting RLX clinical trial data. For comparison of safety and efficacy, post-marketing studies on RLX were included.
EXPERT OPINION
RLX is effective in reducing vertebral fracture risk in osteoporotic women, it is safe and its ability to prevent breast cancer has to be considered in the analyses of cost/effect and of the ideal candidate to this treatment. RLX has to be avoided in patients with previous history of venous thromboembolism.
Topics: Bone Density Conservation Agents; Breast Neoplasms; Clinical Trials as Topic; Cost-Benefit Analysis; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Spinal Fractures
PubMed: 23521229
DOI: 10.1517/14656566.2013.782002 -
Experimental Gerontology Mar 2022Raloxifene treatment has been reported to be associated with cardiovascular benefits if prescribed to women during the postmenopausal period. However, a final conclusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Raloxifene treatment has been reported to be associated with cardiovascular benefits if prescribed to women during the postmenopausal period. However, a final conclusion regarding this hypothesis has not yet been achieved. We conducted a systematic review and meta-analysis to evaluate the effect of raloxifene on the endothelial function and inflammation in postmenopausal women.
METHODS
We systematically searched the following 4 databases from inception to 23 January 2021 without any language restrictions: Web of Science, PubMed/Medline, Embase and Scopus. The eligible randomized controlled trials (RCTs) reporting the effects of raloxifene on the flow-mediated dilatation (FMD), C-reactive protein (CRP), carotid intima-media thickness (CIMT), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin levels, were included in the final meta-analysis.
RESULTS
A total of 16 RCTs were included in the final analysis. Raloxifene administration had no significant effect on ICAM-1 and E-selectin levels. However, we observed a decrease of the CIMT (WMD: -0.071 mm, 95% CI: -0.09 to -0.04, P = 0.000), CRP (WMD: -0.342 mg/L, 95% CI: -0.591, -0.094, p = 0.007), and VCAM-1 (WMD: -197.90 mg/L, 95% CI: -269.58 to -126.23, P = 0.000) levels in the intervention versus control groups following the prescription of this pharmacological agent. Moreover, raloxifene treatment resulted in a significant elevation of the FMD (WMD: 1.64%, 95% CI: 0.46 to 2.81, P = 0.006), particularly if the intervention was equal to or exceeded 12 weeks.
CONCLUSION
Raloxifene might emerge as a potential therapeutic option in the management of endothelial dysfunction and inflammation in postmenopausal women.
Topics: Biomarkers; Female; Humans; Inflammation; Postmenopause; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 34973344
DOI: 10.1016/j.exger.2021.111682