Treatment Of Postmenopausal Osteoporosis Research Articles

Update over de diagnose en behandeling van postmenopauzale osteoporose

Update on the diagnosis and treatment of postmenopausal osteoporosis Osteoporosis is characterized by a low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in spontaneous or low-impact fractures. These fractures are associated with a significant impact on morbidity and mortality. This article provides a literature overview of the most recent guidelines of the Belgian Bone Club with regard to screening, diagnosis, treatment and follow-up of postmenopausal osteoporosis. The Belgian Bone Club recommends screening for osteoporosis in all women ≥ 50 years, or at the age of menopause if this occurs earlier. After a positive screening, the guidelines recommend an evaluation of previous fragility fractures, a measurement of bone mass by DXA and a calculation of the fracture risk with computer-based algorithms. Based on these three criteria, we categorize the fracture risk as low, high or very high. Lifestyle measures and sufficient calcium and vitamin D intake are recommended in all categories. Antiresorptive treatment should be considered for high-risk patients (selective estrogen receptor modulators, bisphosphonates or the anti-RANK antibody denosumab). For patients at very high-risk, anabolic therapy, such as teriparatide or romosozumab, is preferred. All anabolic therapy should be followed by antiresorptive therapy. It is recommended to regularly monitor the effectiveness and tolerance of therapy, including a DXA measurement every 2 to 5 years.

Mechanistic Insights into Kaempferol's Therapeutic Effects on Postmenopausal Osteoporosis: A Proteomic and Experimental Validation in Ovariectomized Rats.

Postmenopausal Osteoporosis (PMOP) is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to increased fracture risk. Current treatments often have adverse effects, necessitating safer alternatives. Kaempferol, a flavonoid identified as a key active component of the traditional Chinese medicine Yishen Gushu formula, has shown promise in improving bone health, but its mechanisms in PMOP treatment remain unclear. The aim of this study was to investigate the therapeutic effects and underlying mechanisms of kaempferol in the treatment of PMOP. A bilateral ovariectomized (OVX) rat model was established to simulate PMOP. Sixty female Sprague-Dawley rats were divided into six groups: Sham operation, OVX control, OVX with alendronate (ALN), and OVX with kaempferol at doses of 10, 20, and 40 mg/kg. Treatments were administered orally once daily for 12 weeks. Assessments included Bone Mineral Density (BMD), trabecular microarchitecture via histopathology, organ morphology, organ indices, and serum levels of bone metabolism markers (TRACP-5b, BALP, ALP, Ca, P, and Fe) as well as liver and kidney function indicators (ALT, AST, CREA, and urea). Tandem Mass Tag (TMT) quantitative proteomics and bioinformatics analyses were conducted on femur samples to identify differentially expressed proteins (DEPs). Key DEPs were validated using parallel reaction monitoring (PRM), immunohistochemistry, and molecular docking. Kaempferol significantly improved BMD and enhanced trabecular microarchitecture in OVX rats in a dose-dependent manner, comparable to ALN, without causing hepatic, renal, or estrogen- like side effects. Serum bone metabolism markers were normalized with kaempferol treatment. Proteomic analysis identified 902 DEPs associated with kaempferol treatment, involved in processes such as bone remodeling, skeletal system development, and osteoclast function. Key signaling pathways affected included NF-κB, PI3K-AKT, and HIF-1. Notably, kaempferol downregulated five key DEPs-Rac2, Ddb1, Cdc42, Rpl19, and Hist2h4-in the femur, which are crucial for osteoclast resorptive activity, migration, adhesion, and cell cycle progression. Kaempferol exerts therapeutic effects on PMOP by inhibiting key proteins involved in osteoclast function, thereby reducing bone resorption and promoting bone health. These findings suggested that kaempferol is a potential safer alternative for PMOP treatment. Further research is recommended to explore its clinical applications and elucidate detailed mechanisms.

17β-estradiol promotes osteogenic differentiation of BMSCs by regulating mitophagy through ARC

The study aims to elucidate the mechanism through which 17β-estradiol facilitates osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). In our study, lentiviral transfection was employed to establish apoptosis repressor with caspase recruitment domain (ARC) knockdown or overexpression in BMSCs. The impact of 17β-estradiol on ARC expression was assessed using western blot, RT-PCR and immunofluorescence. Techniques such as ALP staining, ALP activity assay, western blot, RT-PCR and immunofluorescence staining were utilized to examine the influence of ARC expression levels on the osteogenic differentiation of BMSCs and the osteoclastic differentiation of Raw264.7 cell lines. Mitophagy flux levels in BMSCs were detected using the mitophagy detection kit. RNA sequencing and bioinformatics analyses were conducted to explore potential mechanisms of ARC regulation in BMSCs osteogenic differentiation. To sum up, 17β-estradiol can modulate bone homeostasis by adjusting ARC expression. ARC stimulates mitophagy in BMSCs via MAPK/Akt pathway, identifying ARC as a promising therapeutic target for postmenopausal osteoporosis (PMOP) treatment.

Transcriptional regulation of Rankl by Txnip-Ecd in aging and diabetic related osteoporosis.

Bone homeostasis between osteoclast bone resorption and osteoblastic bone formation is tightly regulated by a series of factors such as the receptor activator of nuclear factor-κB ligand (RANKL). Denosumab that neutralizes RANKL is effective and widely applied in the treatment of postmenopausal osteoporosis. However, factors that participated in the RANKL-related bone remodeling process in primary and secondary osteoporosis are less known. Revealing the novel transcriptional regulatory mechanism of RANKL is of great significance for the treatment of osteoporosis. After differential expression genes (DEGs) intersection and screening, we generated Thioredoxin-interacting protein (Txnip) bone marrow-derived mesenchymal stromal cells (BMSCs) genetic knockout mice and performed bone histomorphometry and histological analysis. RNA-Sequencing, Western blotting and immunofluorescence staining verified Rankl downregulation. Co-immunoprecipitation and immunofluorescence staining were used for Rankl regulation mechanism exploration. A specific inhibitor was selected for treatment effect verification. Txnip knockout in BMSCs impaired its osteogenic differentiation, suppressed Rankl expression and subsequent osteoclast formation and thus led to increased bone mass. The regulatory function of Txnip on Rankl expression was revealed for the first time through the novel transcription-related Ecdysoneless (Ecd)-P300 axis. Pharmacological inhibition of Txnip can effectively prevent bilateral ovariectomy (OVX)-induced osteoporosis. Inhibition of Txnip is an alternative way to suppress Rankl-mediated osteoblast and osteoclast crosstalk. This interesting finding rendered Txnip an ideal therapeutic target for the treatment of both ovariectomy-induced and diabetes-induced osteoporosis.

Compromised anti-osteoclastogenic and immunomodulatory functions of regulatory B cells (Bregs) aggravate inflammatory bone loss in post-menopausal osteoporosis.

Regulatory-B-cells (Bregs) modulate immune-homeostasis. Variations in the number and function of Bregs have been associated with various immune-related ailments, highlighting the importance of Bregs under inflammatory-conditions. Previously, we discovered the anti-osteoclastogenic-potential of Bregs. However, the crucial role of Bregs in the onset and progression of post-menopausal osteoporosis (PMO) has never been explored. Interestingly, our temporal-kinetic study demonstrated that Bregs have a compromised dynamics and functionality which further contributes to inception and the progression of the inflammatory bone loss condition in the PMO. Our ex-vivo findings further elucidate a significant reduction in the immunomodulatory and anti-osteoclastogenic functions of Bregs under the estrogen deficient post-menopausal osteoporotic conditions. The current study for the first time reports the crucial role of dysregulated-Bregs (both functionally and numerically), in the development of PMO. Our findings thereby provide a novel concept for immuno-therapeutically targeting "Bregs", for effective management and treatment of post-menopausal osteoporosis in the long run.

Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.

A real‑world pharmacovigilance study of raloxifene based on the FDA adverse event reporting system (FAERS)

ABSTRACT Background Raloxifene was approved for the treatment of postmenopausal osteoporosis; however, its safety profile remains inadequately understood. This study aimed to evaluate the safety signals associated with raloxifene. Research design and methods Adverse events (AEs) related to raloxifene, spanning from the first quarter of 2004 to the fourth quarter of 2023, were extracted from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was conducted using several methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Results The analysis yielded 7 229 reports related to raloxifene across 19 277 AEs. A total of 217 significantly disproportionate signals were identified, including muscle spasms and hot flashes. Notably, the study also uncovered novel AEs, including eye conditions like cataracts and macular degeneration, as well as gynecological issues like uterine polyps and hemorrhage. Additionally, the analysis confirmed that pulmonary embolism and deep vein thrombosis were the two most prevalent thromboembolic AEs. Conclusion Our study reaffirmed some existing safety information regarding raloxifene while also unveiling novel risk signals. The findings provided crucial insights to enhance the rational use of the drug and inform safety regulatory strategies.

Modern Strategies for the Prevention and Treatment of Postmenopausal Osteoporosis

Modern Strategies for the Prevention and Treatment of Postmenopausal Osteoporosis

Sarsasapogenin stimulates angiogenesis and osteogenesis coupling to treat estrogen deficiency-induced osteoporosis by activating the GPX4/SLIT3/ROBO1 axis

BackgroundPromoting the coupling of osteogenesis and angiogenesis is a crucial strategy for the treatment of postmenopausal osteoporosis (PMOP). Estrogen deficiency induces ferroptosis, which is closely associated with the pathophysiology of PMOP. Sarsasapogenin (SAR) is a natural sapogenin with anti-oxidative effects. However, it is unclear whether SAR has a protective role against the impaired osteogenesis and angiogenesis coupling in PMOP. In this study, we evaluated the efficacy of SAR in estrogen deficiency-induced osteoporosis and explored the underlying mechanisms. MethodsBone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) were utilized to assess the in vitro effects of SAR on the coupling of osteogenesis and angiogenesis. In vivo experiments involved bilateral ovariectomy (OVX)-induced osteoporosis in mice and glutathione peroxidase 4 (GPX4)-knockout (KO) mice. Mice were orally administered SAR (5 or 10 mg/kg/d) for a duration of 12 weeks. The direct target of SAR was investigated through molecular docking, a cellular thermal shift assay, and surface plasmon resonance. Additionally, RNA sequencing was employed to elucidate the underlying mechanisms. ResultsSAR treatment improved cell viability and osteogenic differentiation while inhibiting ferroptosis in iron dextran-induced BMSCs. Furthermore, SAR enhanced the production of slit guidance ligand 3 (SLIT3) in these cells, which stimulated angiogenesis by activating its receptor, roundabout human homolog 1 (ROBO1), in HUVECs. An in vitro model of ferroptosis induced by erastin demonstrated that SAR promoted the coupling of osteogenesis and angiogenesis by upregulating the BMSCs-SLIT3/HUVECs-ROBO1 axis. Activation of GPX4 was identified as a contributing factor to the effects of SAR on this coupling. Transfection of GPX4 small interfering RNA (siRNA) in BMSCs negated the impact of SAR on the BMSCs-SLIT3/HUVECs-ROBO1 axis. Additionally, SAR was found to directly interact with GPX4, enhancing protein stability, with an equilibrium dissociation constant of 44.6 μM. Notably, SAR did not increase SLIT3, ROBO1, or indicators of osteogenesis or angiogenesis in GPX4-KO mice. ConclusionsThese findings underscore the significance of restoring the GPX4/SLIT3/ROBO1 axis in promoting the coupling of angiogenesis and osteogenesis. SAR mitigates PMOP, in part, by activating the BMSCs-SLIT3/HUVECs-ROBO1 axis, with GPX4 serving as an upstream signaling modulator responsible for SLIT3 production. Our observations provide experimental evidence supporting the clinical application of SAR in the treatment of PMOP.

Sequential treatment from bisphosphonate to denosumab improves lumbar spine bone mineral density in postmenopausal osteoporosis patients: A meta-analysis of randomized controlled trials.

Bisphosphonates are effective in the treatment of postmenopausal osteoporosis. However, their prolonged use induces adverse events and may lead to a rapid decline in bone mineral density (BMD) after discontinuation. Denosumab, a human monoclonal antibody, is a widely used antiresorptive agent that is more effective than bisphosphonates in improving bone density. Whether sequential treatment with denosumab after bisphosphonate therapy can maintain or further increase BMD at all sites has not been conclusively demonstrated. Thus, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of this sequential therapy on BMD. We searched the PubMed, Embase, and Cochrane Library databases from December 1, 1986, to May 2, 2024, for all RCTs that assessed the efficacy of sequential therapy of bisphosphonate transition to denosumab in postmenopausal women with osteoporosis. BMD changes at the lumbar spine, femoral neck, and total hip were used as outcomes. We assessed methodological quality, extracted relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions, applied random-effects models for meta-analyses, performed heterogeneity analyses, and assessed publication bias. A total of 3290 patients from 4 RCTs were included in the meta-analysis. Forest plot analysis showed that sequential treatment with bisphosphonate-denosumab was associated with higher lumbar spine BMD gain than continuous bisphosphonate treatment [mean difference (MD) = 5.50, 95% confidence interval (CI) = 5.26-5.75, I2 = 32.88%). No risk of bias was observed for the 4 trials, but there was an increase in femoral neck and total hip BMD. Moreover, analyses could not be performed because of high heterogeneity (femoral neck BMD: MD = 3.85, 95% CI = 2.84-4.85, I2 = 97.88%; total hip BMD: MD = 5.65, 95% CI = 4.28-7.02, I2 = 97.91%). Sequential therapy that involves a transition from bisphosphonates to denosumab had a positive effect on lumbar spine bone density, and this type of therapy may be a potential treatment option for increasing lumbar spine bone density in postmenopausal women.

Clinical efficacy and outcomes of calcitriol combined with bisphosphonates in the treatment of postmenopausal osteoporosis: A quasi-experimental study.

A quasi-experimental study was conducted to investigate the clinical efficacy and outcomes of calcitriol combined with bisphosphonates in the treatment of postmenopausal osteoporosis (OP). A total of 152 patients with postmenopausal OP from March 2019 to June 2021 were enrolled. The patients who received calcitriol treatment were adopted as the control group, and the patients treated with calcitriol combined with bisphosphonates were considered as the intervention group. The treatment effects of patients were compared, and the pain degree of the joints of the patients was evaluated by Visual Analogue Scale/Score (VAS), the Barthel Index score was used to evaluate the daily living ability of patients, the hand and Oswestry Disability Index (ODI) were used to evaluate the dysfunction before and after treatment, and the bone metabolism indexes, immune cytokines and bone mineral density were detected before and after treatment, and the incidence of adverse reactions was calculated. Regarding the therapeutic effects, the intervention group indicated an effective rate of 96.05% while the effective rate was 84.21% in the control group. The total effective rate of treatment in the intervention group was higher than the control group. The VAS, ODI scores, and bone metabolism indexes of the intervention group were significantly lower than the control group at 1, 2, and 3 months after treatment. The Barthel Index scores and bone mineral density of the intervention group were higher than the control group at 1, 2, and 3 months after treatment. The improvement of immune cytokines in the intervention group was significantly better than the control group (P < .05). One patient in the intervention group developed dizziness and 1 patient developed chills, with an adverse reaction rate of 2.63%, while in the control group, 2 patients had fever, and 2 patients developed chills, with an adverse reaction rate of 5.26% (P > .05). Calcitriol combined with bisphosphonates has a significant clinical effect in the treatment of postmenopausal OP, which can significantly relieve bone pain in postmenopausal OP patients, enhance abnormal bone metabolism and immune function, and promote bone mineral density and daily living ability.

Yigu decoction regulates plasma miRNA in postmenopausal osteoporosis patients: a randomized controlled trial.

Postmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD. In this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism. Compared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins. This study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

Оценка эффективности препаратов золедроновой кислоты для парентерального введения

Bisphosphonates are one of the main drugs for the treatment of postmenopausal osteoporosis. This group of drugs includes zoledronic acid (zoledronate), used for intravenous administration. Zoledronic acid has an antiresorptive effect and is used to treat various bone diseases, including osteoporosis. Currently, generic preparations of zoledronic acid, including Osteostatics, have become widespread. Aim – to compare the effectiveness of the generic preparation of zoledronic acid 5 mg (Osteostatics) with the original preparation of zoledronic acid 5 mg (Aclasta) in postmenopausal osteoporosis. Material and methods. During 2021–2022, we examined 139 patients with postmenopausal osteoporosis. The patients were divided into two groups. The first group (69 people) received a generic drug (generic) of zoledronic acid Osteostatics. The second group (70 people) is the original preparation of zoledronic acid Aclasta. All patients additionally received 1000 mg of calcium carbonate and 2000 IU of vitamin D daily. Patients of both groups repeated measurement of bone mineral density (BMD) 6 and 12 months after infusion of zoledronic acid. Results. After 6 months and 12 months after treatment, both groups showed a statistically significant increase in BMD in both the lumbar spine and hip neck, compared with the baseline level. At the same time, there were no differences between the increase in BMD between the two groups of patients receiving Osteostatics and Aclasta. The dynamics of the increase in BMD after 6 months and 12 months after the infusion of zoledronic acid indicates a similar effectiveness of the original and generic drugs. Conclusion. Effectiveness of the generic preparation of zoledronic acid Osteostatics at a dose of 5 mg is comparable to the original preparation Aclasta.

Shen Gu An Capsule Inhibition of Postmenopausal Osteoporosis in Ovariectomized Mice Using Network Pharmacology-Based Mechanism Prediction and Pharmacological Validation

Background Postmenopausal osteoporosis (PMOP) is characterized by low bone mass and increased bone fragility in postmenopausal women. Shen Gu An capsule (SGA) has been clinically used to treat bone diseases, especially PMOP with kidney Yang deficiency. Objectives We aimed to study the effect of SGA on the treatment of PMOP. Methodology The key candidate targets and pathways of SGA for treating PMOP were predicted by Network pharmacology analysis. Then, in vivo validation using bilaterally ovariectomized C57BL/6 mice was performed, and the bone quality was analyzed by Micro-CT and histological analysis. Results In this study, we obtained 113 active compounds and 82 targets via the database of Traditional Chinese Medicine Systems Pharmacology. Subsequently, compound-target and protein−protein interaction networks were constructed. Then GO and KEGG analysis revealed that NF-κB signaling pathway might be the underlying mechanism as its well-known function in osteoclastogenesis. Furthermore, the in vivo experiments using ovariectomized mice demonstrated that SGA could decrease the number of osteoclasts and preserve bone mass through inhibiting the NF-κB signaling pathway. Conclusions SGA could prevent postmenopausal osteoporosis in ovariectomized mice through inhibiting NF-κB signaling pathway. The finding of this study provides more evidence for the clinical application of SGA to treat osteoporosis.

Dynamic transcriptome analysis of osteal macrophages identifies a distinct subset with senescence features in experimental osteoporosis.

Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence, and apoptotic process. A single-cell RNA-Seq analysis revealed that osteal macrophages were heterogeneously clustered into 6 subsets that expressed proliferative, inflammatory, antiinflammatory, and efferocytosis gene signatures. Importantly, postmenopausal mice exhibited an increase in subset 3 that showed a typical gene signature of cell senescence and inflammation. These findings suggest that the decreased production of estrogen due to postmenopausal condition altered the osteal macrophage subsets, resulting in a shift toward cell senescence and inflammatory conditions in the bone microenvironment. Furthermore, adoptive macrophage transfer onto calvarial bone was performed, and mice that received oxidatively stressed macrophages exhibited greater osteolytic lesions than control macrophages, suggesting the role of these cells in the development of inflammaging in the bone microenvironment. Consistently, depletion of senescent cells and the oxidatively stressed macrophage subset alleviated the excessive bone loss in postmenopausal mice. Our data provided insight into the pathogenesis of osteoporosis and shed light on a therapeutic approach for the treatment or prevention of postmenopausal osteoporosis.

Effects of Cannabidiol on Bone Quality in Ovariectomized Rats.

The incidence of osteoporosis and related fractures increases significantly with age, impacting public health and associated costs. Postmenopausal osteoporosis results from increased bone resorption due to decreased estrogen levels. The endocannabinoid system, especially cannabidiol (CBD), has shown therapeutic potential in modulating bone formation. This study investigated the effects of administration of CBD in rats after the onset of with ovariectomy-induced osteopenia (OVX). Forty-eight female Sprague‒Dawley rats were divided into four groups (n = 12): OVX + CBD, SHAM + CBD, OVX + vehicle, and SHAM + vehicle. CBD was administered intraperitoneally for 3weeks. After euthanasia, the bone quality, mechanical properties, and bone microarchitecture of the femurs and lumbar vertebrae were assessed by microcomputed tomography (micro-CT), bone densitometry, mechanical tests, and histological and immunohistochemical analyses. CBD treatment improved the bone mineral density (BMD) of the lumbar vertebrae and increased the BV/TV% and Tb.N in the femoral neck. There were also improvements in the mechanical properties, such as the maximum force and stiffness of the femurs and vertebrae. CBD significantly increased the bone matrix in osteopenic femurs and vertebrae, Although did not significantly influence the expression of RANKL and OPG, in ovariectomized animals, there was an increase in osteoblasts and a decrease in osteoclasts. Determining the optimal timing for CBD use in relation to postovariectomy bone loss remains a crucial issue. Understanding when and how CBD can be most effective in preventing or treating bone loss is essential to emphasize the importance of early diagnosis and treatment of osteoporosis. However, further studies are needed to explore in more detail the efficacy and safety of CBD in the treatment of postmenopausal osteoporosis.

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.

To Explore the Rule and Mechanism of Traditional Chinese Medicine in the Treatment of Postmenopausal Osteoporosis Based on Data Mining, Network Pharmacology and Molecular Docking Technology

Postmenopausal osteoporosis (PMOP) is an important part of primary osteoporosis, and the current clinical treatment program for PMOP is easily limited by side effects and adverse reactions, so it is particularly important to seek more efficient, safe, and economical drug treatment for PMOP. In recent years, with the change of disease treatment mode and the gradual deepening of Traditional Chinese medicine (TCM) research on PMOP, a review of the literature reveals that there is a huge number of studies on the use of TCM in the treatment of PMOP, but there are no relevant systematic studies on the rules of its formulas and the specific mechanisms by which the core drugs exert their therapeutic effects. Therefore, in this study, we collected a total of 141 formulas used by TCM clinicians to treat PMOP, statistically analyzed their high-frequency medications, Four Qi, Five Flavors, meridians, and efficacies, and analyzed the core medications based on the association rules, which were Rehmanniae Radix Praeparata, Epimedium, Eucommia ulmoides, Rhizoma Drynariae, Angelica sinensis, Achyranthes, Astragalus propinquus, Psoralen, Cornus officinalis and licorice. A total of 87 drug pairs were obtained from the correlation analysis, and a total of 8 groups of potential core combination drugs and 4 potential new prescriptions were derived based on the cluster analysis. Subsequently, a network pharmacological analysis of the core drugs was conducted to obtain 173 active ingredients in the core drugs, including kaempferol, β-sitosterol, quercetin, etc. 298 targets of action, including MAPK3, STAT1, HSP90AA1, etc. 170 signaling pathways including AGE-RAGE, PI3 K/Akt, TNF, HIF-1 and others. The molecular docking results showed that 11 key active ingredients in the core drugs had stable binding to the target targets. This study showed that TCM treatment of PMOP is mainly based on “reinforcing liver and kidney, warmly invigorating spleen and stomach, activating blood and resolving stasis.” Core drugs therapy for PMOP is a comprehensive intervention through multi-component, multi-target, and multi-pathway approaches. The minimum binding energies between the 11 key active ingredients and the 11 key targets were calculated in a comprehensive analysis, which shows that the core drugs have good binding activities to their therapeutic targets, proving that the predictions of this study are reliable. In the future, it will provide certain medication basis and data support for TCM treatment of PMOP.

Teriparatide in postmenopausal osteoporosis: uncovering novel insights into efficacy and safety compared to other treatments - a systematic review and meta-analysis.

The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1-34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01-0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00-0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1-34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32-2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45-0.072), with no significant difference observed in mortality rates between treatment and control groups. Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.