Prevention Of Postmenopausal Osteoporosis Research Articles

Retrospective Analysis of the Effect of Postmenopausal Women Medications on SARS-CoV-2 Infection Progression

Since the beginning of the COVID-19 pandemic, it has been evident that women and young people were less susceptible to severe infections compared to males. In a previous study, we observed a reduced prevalence of SARS-CoV-2 infections in hormonal-driven breast cancer patients undergoing SERM (selective estrogen receptor modulator) therapy with respect to other treatments inhibiting estrogen synthesis. In addition to being used in anticancer therapy, SERMs are also prescribed for postmenopausal osteoporosis prevention and treatment. Therefore, in this study, a retrospective analysis of the clinical outcomes of SARS-CoV-2 infections in a population of women over 50 years who were treated for the management of menopausal symptoms was performed. SARS-CoV-2 infections, hospitalizations, and death rates were evaluated in women residing in the Italian north-eastern Veneto Region who were undergoing treatment with Estrogen Modulators (EMs); Estrogen or Progestin, and their combination (EPs); Bisphosphonates (BIs); or cholecalciferol (vitamin D3) ± calcium supplementation (CC). The final cohort study included 124,393 women, of whom 6412 were found to be SARS-CoV-2 infected (CoV2+ve). The results indicated that only women treated with vitamin D3 alone or in combination with calcium showed a significant reduction in their SARS-CoV-2 infection risk by 26% (OR 0.74; 95%CI 0.60–0.91). On the other hand, an increased risk of hospitalization (OR 2.69; 95%CI 1.77–4.07) was shown for the same treatments. The results highlighted in this work contribute to shedding some light on the widely debated role of vitamin D in the prevention of SARS-CoV-2 infections and the disease’s treatment.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential; however, pharmacological treatments are limited. Herein, we evaluate the effect of calcium-fortified fresh milk (FM) in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy. After 3 months of FM (containing vitamin D, and casein phosphopeptides, 1000 mg Ca/100 g) or control milk (110 mg Ca/100 g milk) supplementation, bone changes were assessed using dual-energy X-ray absorptiometry, microcomputed tomography, and bone biomechanical testing. The results revealed that FM can regulate bone metabolism and gut microbiota composition, which act on bone metabolism through pathways associated with steroid hormone biosynthesis, relaxin signaling, serotonergic synapse, and unsaturated fatty acid biosynthesis. Furthermore, FM administration significantly increased bone mineral content and density in the lumbar spine and femur, as well as femoral compressive strength, while improving femoral trabecular bone parameters and microarchitecture. Mechanistically, we found that the effects may be due to increased levels of estrogen, bone formation marker osteocalcin, and procollagen type I N-propeptide, and decreased expression of the bone resorption marker C-telopeptide and tartrate-resistant acid phosphatase 5b. Overall, the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Multilevel categoric factorial design for optimization of raloxifene hydrochloride solid dispersion in PVP K30 by hot-melt extrusion technology

Raloxifene Hydrochloride (RLH) is a selective estrogen receptor modulator (SERM) used for the treatment and prevention of postmenopausal osteoporosis. This Active Pharmaceutical Ingredient (API) belongs to class II biopharmaceutics classification system (BCS) hence it is characterized by solubility-limited bioavailability. The goal of this study is to develop solid dispersion with improved dissolution properties, and enhanced bioavailability via hot-melt extrusion technology. The solid dispersions were made by blending RLH with polyvinylpyrrolidone and polyethylene oxide as polymeric carriers. Design of experiment (DOE) was employed to systematically assess the impact of the formulation variables and their interaction on the drug release profile. The HME conditions were optimized at 165 °C and 150 rpm, ensuring efficient processing. Our findings revealed that Tween 80 and Cremophor RH 40, at a 10 % w/w concentration, served as effective plasticizers for PVP K30. The formulation featuring the highest proportion of PVP K30 (80 % w/w) and Tween 80 as a surfactant exhibited remarkable enhancement of drug release, with over 80 % of the drug dissolving within 30 min and about 100 % within 60 min. The drug has transformed from the crystalline into the amorphous state as confirmed by Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (PXRD), The lead formulation met the USP acceptance criteria for content uniformity, and exhibited a substantial increase in solubility compared to the pure drug across various media.

Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis.

The use of menopausal hormone therapy (MHT) has declined due to concerns about its potential side effects. However, its pivotal role in managing postmenopausal osteoporosis is gaining increased recognition. In this article, we explore how MHT assists postmenopausal women in maintaining bone health and preventing fractures. Recent research indicates that MHT significantly reduces the risk of fractures in women. This benefit is evident regardless of a woman's bone mineral density or their use of progestogens. However, there is limited evidence suggesting that the skeletal benefits continue once the treatment is discontinued. Possible complications of MHT include heart attacks, clots, strokes, dementia, and breast cancer. The most suitable candidates for MHT are women who have recently entered menopause, are experiencing menopausal symptoms, and are below 60 years of age with a minimal baseline risk of adverse events. The treatment is available to those who meet these criteria. For women undergoing premature menopause, MHT can be considered as a means to protect bone health, especially if initiated before menopause or if accelerated bone loss is documented soon after menopause. Such decisions should be made after evaluating individual risk factors and benefits.

Inverse Correlation Between Bone Mineral Density and Systemic Immune Inflammation Index in Postmenopausal Turkish Women.

In this study, the correlation between the change in bone mineral density (BMD) and the numerical value of the systemic immune inflammation index (SII) in postmenopausal Turkish women was investigated. The study comprised patients who had undergone menopause for at least one year and whose blood samples were examined by dual-energy X-ray absorptiometry (DEXA) on the same day. A retrospective evaluation of 527 postmenopausal women was performed. Age, body mass index (BMI), BMD,t score, neutrophil-lymphocyte-platelet-monocyte counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and SII (platelet count x neutrophil count/lymphocyte count) values were calculated andrecorded. When the data were analyzed with the Statistical Package for the Social Sciences (SPSS; IBM SPSS Statistics for Windows, version 26.0. Armonk, NY: IBM Corp.), neutrophil (p<0.001), lymphocyte (p=0.004), monocytes (p=0.002), platelet distribution width (PDW) (p=0.02), procalcitonin (PCT) (p=0.04), erythrocyte sedimentation rate (ESR) (p=0.001), C-reactive protein (CRP) (p=0.001), NLR (p=0.001), PLR (p=0.004), MLR (p=0.003), and SII (p=0.001) values were found to be higher in the postmenopausal osteoporosis (PMO) group than in the normal and osteopenia groups (p<0.05). When the platelet (p=0.15), mean platelet volume (MPV) (p=0.07), and 25-OH vitamin-D (p=0.15) values were compared, no correlation was found between the groups (normal, osteopenia, and PMO) (p>0.05). This study revealed that NLR, PLR, MLR, and SII values were inversely correlated with the change in BMD in postmenopausal Turkish women. These biomarkers, which are obtained from a simple, affordable, and accessible routine blood examination, may play an effective role in the early diagnosis and prevention of PMO in the future.

Knowledge Regarding Prevention of PostMenopausal Osteoporosis: A Community Base Survey

Introduction: Low bone mass and structural bone tissue degeneration are symptoms of osteoporosis, which also increases bone fragility and fracture susceptibility. A significant risk factor for fragility fracture is decreased bone density. Aim/Objectives: The purpose of this study is to evaluate women’s knowledge about post-menopausal osteoporosis prevention. 200 women between the ages of 25 and 50 were chosen from a non-probability purposive sampling of the locations. To gauge knowledge, a semi-structured interview was done. Result: According to the findings, 3.5% of the participants had good knowledge, 27.5% of the subjects had average knowledge, and 69.0% of the subjects had bad knowledge. Conclusion: Thus, it may be said that the bulk of the subjects have inadequate knowledge

Lophatherum gracile Bronghiart Suppresses Receptor Activator of Nuclear Factor Kappa-B Ligand-Stimulated Osteoclastogenesis and Prevents Ovariectomy-Induced Osteoporosis.

Lophatherum gracile Bronghiart, used in traditional herbal medicine, has many biological properties including antiviral, antipyretic, antitumor, vasorelaxation, and neutrophilic inflammatory effects. However, its modulatory effects on bone metabolism have not been investigated previously. In this study, we examined the effects of a water extract of the leaves of L. gracile (WELG) on osteoclast differentiation and bone loss, and explored its underlying mechanisms. We found that WELG inhibits osteoclastogenesis by suppressing both receptor activator of nuclear factor-κB ligand (RANKL)-induced early activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB)- and RANKL-induced modulation of the positive and negative regulators of osteoclastogenesis in osteoclast precursors. In vivo study demonstrated that WELG protects against bone loss, weight gain, and fat accumulation without affecting uterine atrophy in an ovariectomy-induced postmenopausal osteoporosis mice model. In addition, photochemical analysis of WELG identified active constituents known to have bone-protective effects. Overall, the results of this study suggest that WELG can be a potential candidate for therapy and prevention of postmenopausal osteoporosis.

Menopausal Transition: Prospective Study of Estrogen Status, Circulating MicroRNAs, and Biomarkers of Bone Metabolism.

ObjectiveOsteoporosis is associated with an impaired balance between bone resorption and formation, which in turn leads to bone loss and fractures. Many recent studies have underlined the regulatory role of microRNAs (miRNAs) in bone remodeling processes and their potential as biomarkers of osteoporosis. The purpose of this study was to prospectively examine the association of circulating miRNAs and bone biomarkers with estrogen status in women before and after oophorectomy, as well as in oophorectomized women on estrogen therapy.MethodsIn this prospective study, we included 11 women before oophorectomy and hysterectomy and at 201 ± 24 days after the surgery. Another 11 women were evaluated 508 ± 127 days after oophorectomy and hysterectomy and after an additional 203 ± 71 days of estradiol treatment. Serum miRNAs were profiled by sequencing. Estrogen status and biomarkers of bone metabolism were quantified. Bone mineral density was assessed in the lumbar spine.ResultsOur analysis revealed 17 miRNAs associated with estrogen levels. Of those miRNAs that were upregulated with estrogen deficiency and downregulated after estrogen therapy, miR-422a correlated with serum beta-carboxy-terminal type I collagen crosslinks (β-CTX) and procollagen 1 N-terminal propeptide (P1NP); and miR-1278 correlated with serum β-CTX, P1NP, osteocalcin, sclerostin, and Dickkopf-1(Dkk1). In contrast, we found an inverse association of miR-24-1-5p with estrogen status and a negative correlation with serum β-CTX, P1NP, osteoprotegerin, and sclerostin levels.ConclusionThe reported miRNAs associated with estrogen status and bone metabolism could be potential biomarkers of bone pathophysiology and would facilitate studies on the prevention of postmenopausal osteoporosis. Our findings require validation in an extended cohort.

Inhibitory Effect of Ulmus davidiana and Cornus officinalis Extracts on Osteoporotic Bone Loss In Vitro and In Vivo.

Background and Objectives: Traditional herbal medicines are becoming more popular as a complementary medication as they have the advantages of being mostly harmless and safe, causing fewer side-effects than conventional medications. Here, we demonstrate the inhibitory effects of the combination of Ulmus davidiana (UD) and Cornus officinalis (CO) extracts on osteoporotic bone loss. Materials and Methods: This study presented osteogenic effects in primary cultured osteoblasts, pre-osteoblastic MC3T3-E1 cell lines, and osteoclastogenic effects in osteoclasts derived from bone marrow monocytes, and finally, protective effects on bone loss in an ovariectomy (OVX)-induced osteoporotic animal model. Results: A significant increase in alkaline phosphatase (ALP) activity was observed following treatment with UD and CO mixtures (8:2, 7:3, and 5:5 ratios) and individual UD and CO extracts, with the highest ALP activity being detected for the treatment with UD and CO extracts at a 5:5 ratio. An optimal ratio of UD and CO (UC) extract promoted osteoblast differentiation in both pre-osteoblastic cells and primary osteoblasts by increasing osteoblastic markers such as Alpl, Runx2, and Bglap. However, treatment with the UC extract inhibited osteoclast differentiation with a decreased expression of osteoclastogenesis-related genes, including Ctsk, Acp5, Mmp9, and Nfatc1. In addition, UC treatment prevented osteoporotic bone loss in OVX mice and improved impaired skeletal structure parameters. Conclusions: This study suggests that combined UD and CO extracts may be a beneficial traditional medicine for the prevention of postmenopausal osteoporosis.

Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway.

ObjectiveGiven the limitations of current anti-resorption agents for postmenopausal osteoporosis, there is a need for alternatives without impairing coupling crosstalk between bone resorption and bone formation ie. osteoclastogenesis. Puerarin, a unique C-glycoside isoflavonoid, was found to be able to prevent bone loss by inhibiting bone resorption, but the underlying mechanism was controversial. In this study, we investigated the effects of puerarin on osteoclastic differentiation, activation and bone resorption and its underlying molecular mechanism in vitro, and then evaluated the effects of puerarin on bone metabolism using an ovariectomized (OVX) rat model.MethodsIn vitro, the effect of puerarin on osteoclastic cytotoxicity, differentiation, apoptosis, activation and function were studied in raw 264.7 ​cells and mouse BMMs. Mechanistically, osteoclast-related makers were determined by RT-PCR, western blot, immunofluorescence, and kinase activity assay. In vivo, Micro-CT, histology, serum bone biomarker, and mechanical testing were used to evaluate the effects of puerarin on preventing osteoporosis.ResultsPuerarin significantly inhibited osteoclast activation and bone resorption, without affecting osteoclastogenesis or apoptosis. In terms of mechanism, the expressions of protein of integrin-β3 and phosphorylations of Src, Pyk2 and Cbl were lower in puerarin group than those in the control group. Oral administration of puerarin prevented OVX-induced trabecular bone loss and significantly improved bone strength in rats. Moreover, puerarin significantly decreased trap positive osteoclast numbers and serum TRAP-5b, CTx1, without affecting bone formation rate.ConclusionsCollectively, puerarin prevented the bone loss in OVX rat through suppression of osteoclast activation and bone resorption, by inhibiting integrin-β3-Pyk2/Cbl/Src signaling pathway, without affecting osteoclasts formation or apoptosis.Translational potential of this articleThese results demonstrate the unique mechanism of puerarin on bone metabolism and provide a novel agent for prevention of postmenopausal osteoporosis.

Methyl-CpG-binding protein 2 promotes osteogenic differentiation of bone marrow mesenchymal stem cells through regulating forkhead box F1/Wnt/β-Catenin axis

ABSTRACT Postmenopausal osteoporosis is characterized by inadequate bone formation of osteoblasts and excessive bone resorption of osteoclasts. Bone marrow mesenchymal stem cells (BMSCs), with the potential of osteogenic differentiation, have been widely used in the bone tissues engineering for the treatment of bone diseases, including postmenopausal osteoporosis. Methyl-CpG-binding protein 2 (MECP2) has been reported to be implicated in bone formation during the development of Rett syndrome. However, the influence of MeCP2 on osteogenic differentiation of BMSCs during osteoporosis remains unclear. Firstly, mice model with estrogen deficiency-induced osteoporosis was established through ovariectomy (OVX). MeCP2 was found to be down-regulated in bone tissues and BMSCs of OVX-induced osteoporosis mice. Secondly, over-expression of MeCP2 enhanced the calcium deposition of BMSCs isolated from the OVX-induced osteoporosis mice. Moreover, expression of osteogenic biomarkers including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), collagen type I alpha 1 (COL1A1), and osteocalcin (OCN) was increased in BMSCs by overexpression of MeCP2. Thirdly, over-expression of MeCP2 reduced protein expression of forkhead box F1 (FOXF1) and adenomatous polyposis coli (APC), while enhanced Wnt5a and β-catenin expression in BMSCs. Over-expression of FOXF1 attenuated MeCP2 over-expression-induced decrease of FOXF1 and APC, as well as increase of Wnt5a and β-catenin. Finally, the increased calcium deposition, protein expression of ALP, RUNX2COL1A1 and OCN induced by concomitant overexpression of MeCP2 were also restored by FOXF1 over-expression. In conclusion, MeCP2 promoted osteogenic differentiation of BMSCs through regulating FOXF1/Wnt/β-Catenin axis to attenuate osteoporosis. MeCP2 over-expression reduced FOXF1 to promote the activation of Wnt5a/β-Catenin and promote osteogenic differentiation of BMSCs during the prevention of postmenopausal osteoporosis.

Effect of Educational Program on Adolescent Girl's Awareness regarding Balanced Diet in the Prevention of Postmenopausal Osteoporosis

Effect of Educational Program on Adolescent Girl's Awareness regarding Balanced Diet in the Prevention of Postmenopausal Osteoporosis

Osteoprotective effects of kefir fortified with omega-3 and vitamin C in ovariectomized rats.

Nutritional interventions can be valuable for the prevention of postmenopausal osteoporosis. This study aimed to investigate the effects of kefir fortified with omega-3 and vitamin C on the bone and uterus parameters of ovariectomized rats. Seventy-seven female Sprague-Dawley rats were ovariectomized or sham-operated. The ovariectomized rats were assigned to six groups and received 1 ml/day of distilled water (OVX group), milk, kefir, kefir fortified with omega-3 fatty acids (kefir+ω3), kefir fortified with vitamin C (kefir+vit-C) or kefir fortified with omega-3 and vitamin C (kefir+ω3+vit-C) for 12 weeks. The sham group also received 1ml/day of distilled water. Subsequently, bone mineral content (BMC) and bone mineral density (BMD) of various bones were assessed. Femurs and uteri were harvested for bone ash analysis and histopathological examinations, respectively. Sera were analyzed for carboxy-terminal cross-linked telopeptide of type 1 collagen, procollagen type 1 amino-terminal propeptide, calcium, phosphorous, tumor necrosis factor-α (TNF-α) and total antioxidant capacity levels. Ovariectomy resulted in significant reduction in bone density (P<0.05). Kefir+ω3+vit-C significantly improved BMC of lumbar spine (0.699±0.027 g compared with 0.580±0.018 in the OVX group), and kefir, kefir+vit-C and kefir+ω3+vit-C significantly increased BMD of tibia (0.118±0.003 g/cm2, 0.119±0.001 and 0.120±0.004 compared with 0.102±0.005 in the OVX group). Moreover, ovariectomy markedly elevated TNF-α level, which was significantly reversed by kefir+ω3+vit-C. Significant atrophy of the uterus was observed following ovariectomy, although the uterus parameters did not change by any of the interventions. In conclusion, kefir fortified with omega-3 fatty acids and vitamin C may have protective effects against bone loss through suppressing inflammation.

Denosumab for the treatment and prevention of postmenopausal osteoporosis

Denosumab for the treatment and prevention of postmenopausal osteoporosis

Raloxifene as a treatment option for viral infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused corona virus disease 2019 (COVID-19) pandemic and led to mass casualty. Even though much effort has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient cure has been discovered. Drug repurposing or drug repositioning which is a process of investigating pre-existing drug candidates for novel applications outside their original medical indication can speed up the drug development process. Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by FDA in 1997 for treatment and prevention of postmenopausal osteoporosis and cancer. Recently, raloxifene demonstrates efficacy in treating viral infections by Ebola, influenza A, and hepatitis C viruses and shows potential for drug repurposing for the treatment of SARS-CoV-2 infection. This review will provide an overview of raloxifene’s mechanism of action as a SERM and present proposed mechanisms of action in treatment of viral infections.

Study of Isopsoralen on the Postmenopausal Osteoporosis Based on the Network Pharmacology and Bioinformatics

Background: Isopsoralen, which comes from the fruit of the traditional Chinese medicine Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proved to be effective for the treatment of osteoporosis. However, the mechanism underlying ispsoralen’s anti-osteoporotic effects remains unknown. The purpose of this study was to study the effects and mechanisms of isopsoralen’s anti-osteoporosis activity by bioinformatics in combination with in vitro and in vivo experiments. Materials and methods: The targets and biological mechanisms of isopsoralen’s anti-osteoporotic effects were predicted by bioinformatics. Then an ovariectomized (OVX) mice model and a H2O2-induced bone marrow mesenchyml stem cell (BMSCs) model were used to detect the effects of isopsoralen on postmenopausal osteoporosis and to verify the predicted targets. Results: The results predicted that IPRN could protect against osteoporosis through several targets including EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. In vivo and in vitro studies confirmed that isopsoralen could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation of BMSCs damaged by H2O2 by inhibiting oxidative stress and apoptosis. Moreover, isopsoralen could significantly produce the above effects through upregulating estrogen receptors. These findings suggested that isopsoralen might be a therapeutic agent for postmenopausal osteoporosis prevention by acting as an estrogen replacement agent and a natural antioxidant. Conclusion: This study provided a comprehensive functional analysis of isopsoralen on the treatment of osteoporosis and provided a potential drug for the treatment of postmenopausal osteoporosis. Funding Information: This work was supported in part by grants from the National Natural Science Foundation of China [82073851] and Important Science Fund of Science and Technology Bureau of Liaoning Province [2020JH2/10300056]. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal studies complied the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health and all experimental protocols in the current study were approved by the institutional animal care committee of Dalian Medical University (Dalian, China; Certificate of Conformity: No. SCXK 2018-0007).

Green Tomato Extract Prevents Bone Loss in Ovariectomized Rats, a Model of Osteoporosis.

Although drug therapies are available for postmenopausal osteoporosis, these drugs are not free of side effects and long-term adherence to them are low. A safe and effective nutritional approach to counter postmenopausal osteoporosis is an important research goal. We fed ovariectomized (OVX) Sprague–Dawley rats a diet supplemented with 1% or 2% green tomato extract (GTE). After 12 weeks, micro-computed tomography scans revealed that GTE supplementation effectively prevented distal femur bone loss. This prevention was due to improved bone formation and suppressed bone resorption as observed by the regulation of osteoblast and osteoclast activities. GTE supplementation also improved bone formation through Bmp2-Smad 1/5/8-Runx2 signaling, while bone resorption was regulated by the receptor activator of nuclear factor kappa-B (RANKL)/osteoprogeterin (OPG) pathway. These results suggest that GTE supplementation prevents severe postmenopausal bone loss by maintaining the regulation of bone homeostasis in OVX rats. GTE as a diet supplement might be a potential novel alternative for the prevention of postmenopausal osteoporosis.

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity, dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r2) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.

Current understanding of selective estrogen receptor modulators

Despite the variety of selective estrogen receptor modulators of different classes of compounds and their active use for the treatment of hormone-dependent breast cancer, climacteric conditions, and polycystic ovary syndrome, as well as for ovulation stimulation and for prevention and treatment of postmenopausal osteoporosis and vertebral fractures, there are a number of serious side effects, such as thromboembolic disorders, uterine cancer and endometrial cancer. Among the selective estrogen receptor modulators used in clinical practice, it is worth noting: Raloxifene, for the prevention and treatment of postmenopausal osteoporosis and vertebral fractures; Tamoxifen, for the treatment of breast cancer; Toremifene, for the treatment of metastatic breast cancer in postmenopausal women; Lasofoxifene, for the treatment of osteoporosis; Bazedoxifene, for the treatment and prevention of postmenopausal osteoporosis; Clomiphene, for the treatment of anovulatory infertility; Ospemifene, for the treatment of moderate to severe dyspareunia associated with postmenopausal syndrome. An ongoing search for an effective and safe selective estrogen receptor modulator for the treatment of endometriosis is currently underway.

Flufenamic acid inhibits osteoclast formation and bone resorption and act against estrogen-dependent bone loss in mice

Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. Nonsteroidal anti-inflammatory drugs (NSAIDs) are important drugs for pain relief in patients with osteoporosis. In this study, we report for the first time that flufenamic acid, a clinically approved and widely used NSAID, not only has analgesic properties but also shows a significant effect in terms of preventing postmenopausal osteoporosis. Quantitative RT-PCR analysis showed that treatment with flufenamic acid significantly downregulated the genes associated with osteoclast differentiation. Meanwhile, RNA-sequencing and western blot analyses suggested that flufenamic acid could inhibit the bone resorption by suppressing the phosphorylation of MAPK pathways. Moreover, an ovariectomy (OVX)-induced bone-loss mouse model indicated that flufenamic acid might be a potent drug for preventing osteoporotic fractures, as verified by micro-CT scanning and histological analysis. Therefore, this study proposes an attractive and potent drug with analgesic properties for the prevention of postmenopausal osteoporosis.