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 ameliorat...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 typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.展开更多
Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes...Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.展开更多
Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wid...Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.展开更多
Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight fema...Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.展开更多
Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine ther...Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.展开更多
[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain sympt...[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain symptoms of osteoporosis.[Methods]Randomized controlled trials(RCTs)of salmon calcitonin in the treatment of osteoporosis from January 2000 to March 2015 were collected by searching Chinese Biomechanics Literature Database(SinoMed,CBM),China National Knowledge Infrastructure(CNKI),VIP and Wanfang Database.The relevant data of bone pain degree and bone mineral density were extracted to evaluate the methodological quality.Meta-analysis was performed using RevMan 5.1 software.A total of 13 randomized controlled trials involving 1683 patients were included,including 862 patients in the observation group and 821 patients in the control group.[Results]Meta-analysis showed that salmon calcitonin combined with calcium was better than the control group in improving bone pain symptoms in osteoporosis patients,and the difference was statistically significant[RR=1.84,95%CI(1.56,2.18)].[Conclusions]The salmon calcitonin can significantly improve the bone pain symptoms of the osteoporosis patients,and has no serious adverse reaction.However,due to the small number of studies included in this systematic review and the small sample size,it still needs to be confirmed by high-quality,large sample,multi-center randomized controlled trials.展开更多
BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the...BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field.展开更多
Osteoporosis is a disease that decreases bone mass and increases bone porosity, weakening bones. The Paleo diet is an eating plan that imitates the dietary patterns of the Stone Age. It excludes grains, dairy, and pro...Osteoporosis is a disease that decreases bone mass and increases bone porosity, weakening bones. The Paleo diet is an eating plan that imitates the dietary patterns of the Stone Age. It excludes grains, dairy, and processed foods and emphasizes feeding on lean meats, fruits, vegetables, and nuts. Consumption of the Paleo diet has many positive sides, such as high protein intake and weight loss. Still, excluding dairy products risks calcium and vitamin D deficiencies, which are crucial for bone health. Statistics and simulations that have explored the relationship between the Paleo diet and bone health (especially for people suffering from low bone density) show mixed outcomes on bone health.). While the consumer does get lots of benefits from fruit and vegetable intake in a large sum due to them containing nutrients like magnesium, potassium, and vitamin K (which are also necessary for bone health), the lack of dairy products (gives the maximum amount of calcium and vitamin D) raises concerns about maintaining adequate bone mineral density (BMD). More information on this topic shows the negative impact of this diet on people suffering from osteoporosis due to a lack of nutrient intake that nourishes the bone. Although the Paleo diet can enhance overall health through nutrient-dense foods and reduced processed intake, it can’t be said the same for people suffering from osteoporosis.展开更多
BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by...BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.展开更多
Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of ...Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.展开更多
Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to pr...Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.展开更多
Objective:To investigate and thoroughly understand the physical examination results of retired employees from a certain unit in Beijing,analyze their bone mineral density(BMD),and identify risk factors that may indica...Objective:To investigate and thoroughly understand the physical examination results of retired employees from a certain unit in Beijing,analyze their bone mineral density(BMD),and identify risk factors that may indicate osteoporosis.This provides a reference for the individualized prevention,identification,and control of osteoporosis among retired employees.Methods:The bone mineral density and potential factors of 148 retired employees from a unit in 2023 were analyzed and categorized into osteoporosis and non-osteoporosis groups.Key factors from the physical examinations of the two groups were compared.Spearman’s correlation analysis was used to determine the correlation between key factors and osteoporosis.Significant key factors were included in a regression analysis.A multivariate binary logistics regression was employed to identify risk factors indicative of osteoporosis.Results:Correlation analysis revealed that gender,age,and ECG ST-segment length were significantly associated with osteoporosis.Regression analysis showed that for each additional year of age,the likelihood of developing osteoporosis increased by 1.058 times;females were 2.865 times more likely to develop osteoporosis compared to males;the longer the ECG ST-segment,the higher the likelihood of osteoporosis.Conclusion:Gender,age,and ECG ST-segment length are significantly associated with osteoporosis.These indicators can provide reference points for early identification,early intervention,and reducing the incidence of osteoporosis in clinical settings.展开更多
Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing...Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.展开更多
Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has re...Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.展开更多
Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel...Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.展开更多
Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite thedevelopment of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their lowbioav...Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite thedevelopment of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their lowbioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. Thiscalls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybridstructures with bioactive components and stable fluffy topological morphology by cross-linking calcium andphosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequentgrafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealedthat these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecularmechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that smalldoseAL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivoresults restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as theconsequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant withpeculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well asbone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies forother bone diseases.展开更多
Objective:To estimate the bone protective effect of alpinumisoflavone,a natural prenylated isoflavonoid,against glucocorticoid-induced osteoporosis in rats.Methods:Male Wistar rats received intramuscular administratio...Objective:To estimate the bone protective effect of alpinumisoflavone,a natural prenylated isoflavonoid,against glucocorticoid-induced osteoporosis in rats.Methods:Male Wistar rats received intramuscular administration of dexamethasone(4 mg/mL)at a dose level of 7 mg/kg for 5 weeks,and then alpinumisoflavone(5,10,and 15 mg/kg)and alendronate(2 mg/kg)from 2 weeks.The body weight and organ weight(femoral,vagina,and uterus)were estimated.MicroCT analysis,bone turnover markers,bone parameters,oxidative stress parameters,and inflammatory cytokines were estimated.mRNA expressions of related genes were also estimated.Results:Alpinumisoflavone remarkably boosted body weight and organ weight(ureters and vagina),improved microCT analysis parameters,and boosted levels of bone markers.Besides,alpinumisoflavone considerably(P<0.001)restored the level of bone turnover markers and oxidative stress parameters,remarkably suppressed the level of cytokines such as interleukin-1β,interleukin-6,tumor necrosis factor-α,and increased transforming growth factor-βand insulin-like growth factor.It also significantly restored the osteoprotegerin(OPG,RANKL,and OPG/RANKL ratio)levels and the mRNA expression of Caspase(3,6,7,9),BMPs,OPN,ALP,RUNX2,and OCN.Conclusions:The current result suggests the bone protective effect of alpinumisoflavone against glucocorticoid-induced osteoporosis in rats.展开更多
Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Phy...Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Physical Activity in Osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic characteristics.Bone mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort.Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong community.Based on their PA level,participants were categorized as inactive,moderately active,or very active.Men showed higher physical exercise levels than women across the activity groups.BMD was significantly higher in the very active group than in the moderately active and inactive groups.Individuals aged>50 years are at a higher risk of developing OP and osteopenia.Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.展开更多
Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
Introduction: Computed tomography (CT) measurements of bone mineral attenuation may be a useful means to identify older women who should be prioritized for bone mineral density screening. Methods: We compared bone min...Introduction: Computed tomography (CT) measurements of bone mineral attenuation may be a useful means to identify older women who should be prioritized for bone mineral density screening. Methods: We compared bone mineral attenuation as measured in the L1 vertebra of CT studies to the results of dual-energy x-ray absorptiometry (DEXA) studies to determine what CT attenuation thresholds might yield a reasonable combination of sensitivity and specificity for the detection of osteoporosis. The study was limited to women between the ages of 65 and 75 years who had a DEXA study and a CT that included the L1 or adjacent vertebra performed within 3 years of the DEXA study. Results: There were 1226 women in this study, of whom 452 (38%) had osteoporosis based on a T-score ≤ −2.5 by DEXA. There were 830 CT studies performed with contrast and 396 studies which were performed without contrast. There was a statistically significant difference in the mean HU of those studies performed without contrast compared to those with contrast (unenhanced mean 103 HU versus 125 HU, p < 0.001). Different CT attenuation thresholds provided the most appropriate combination of sensitivity and specificity for the detection of osteoporosis when comparing CT studies performed without or with IV contrast and when all the CT data were used in aggregate. Conclusion: Different thresholds appear necessary when using the mean CT vertebral attenuation to identify older women for preferential referral for DEXA studies.展开更多
基金supported by the National Natural Science Foundation of China (32072191)Daxing District Major Scientific and Technological Achievements Transformation Project (2020006)+1 种基金Beijing Innovation Team Project of Livestock Industry Technology SystemBeijing Science and Technology Special Project (Z201100002620005)。
文摘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 typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.
基金This research was financially supported by the National Key R&D Program of China(2019YFA0110600)the National Natural Science Foundation of China(82370932,81970917,82370929,81970916,81800947,82101077)+2 种基金the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202102,RD03202302)Sichuan Science and Technology Program(2022NSFSC0002)Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021).
文摘Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.
文摘Objective To investigate the causal relationships between plasma metabolites and osteoporosis via Mendelian randomization(MR) analysis.Methods Bidirectional MR was used to analyze pooled data from different genome-wide association studies(GWAS). The causal effect of plasma metabolites on osteoporosis was estimated using the inverse variance weighted method, intersections of statistically significant metabolites obtained from different sources of osteoporosis-related GWAS aggregated data was determined, and then sensitivity analysis was performed on these metabolites. Heterogeneity between single nucleotide polymorphisms was evaluated by Cochran's Q test. Horizontal pleiotropy was assessed through the application of the MR-Egger intercept method and the MRPRESSO method. The causal effect of osteoporosis on plasma metabolites was also evaluated using the inverse variance weighted method. Additionally, pathway analysis was conducted to identify potential metabolic pathways involved in the regulation of osteoporosis.Results Primary analysis and sensitivity analysis showed that 77 and 61 plasma metabolites had a causal relationship with osteoporosis from the GWAS data in the GCST90038656 and GCST90044600 datasets, respectively. Five common metabolites were identified via intersection. X-13684 levels and the glucose-to-maltose ratio were negatively associated with osteoporosis, whereas glycoursodeoxycholate levels and arachidoylcarnitine(C20) levels were positively associated with osteoporosis(all P < 0.05). The relationship between X-11299 levels and osteoporosis showed contradictory results(all P < 0.05). Pathway analysis indicated that glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, galactose metabolism, arginine biosynthesis, and starch and sucrose metabolism pathways were participated in the development of osteoporosis.Conclusion We found a causal relationship between plasma metabolites and osteoporosis. These results offer novel perspectives with important implications for targeted metabolite-focused interventions in the management of osteoporosis.
文摘Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.
基金supported by the Program of Introducing Talents of Discipline to Universities(111 Project)-TCM Prevention and Treatment of Major Chronic Diseases(Tumor-B21028).
文摘Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.
文摘[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain symptoms of osteoporosis.[Methods]Randomized controlled trials(RCTs)of salmon calcitonin in the treatment of osteoporosis from January 2000 to March 2015 were collected by searching Chinese Biomechanics Literature Database(SinoMed,CBM),China National Knowledge Infrastructure(CNKI),VIP and Wanfang Database.The relevant data of bone pain degree and bone mineral density were extracted to evaluate the methodological quality.Meta-analysis was performed using RevMan 5.1 software.A total of 13 randomized controlled trials involving 1683 patients were included,including 862 patients in the observation group and 821 patients in the control group.[Results]Meta-analysis showed that salmon calcitonin combined with calcium was better than the control group in improving bone pain symptoms in osteoporosis patients,and the difference was statistically significant[RR=1.84,95%CI(1.56,2.18)].[Conclusions]The salmon calcitonin can significantly improve the bone pain symptoms of the osteoporosis patients,and has no serious adverse reaction.However,due to the small number of studies included in this systematic review and the small sample size,it still needs to be confirmed by high-quality,large sample,multi-center randomized controlled trials.
文摘BACKGROUND Postmenopausal osteoporosis(PMOP)is the most common form of primary osteoporosis among women,and the associated pain often drives patients to seek clinical intervention.Numerous studies have highlighted the unique clinical benefits of exercise therapy(ET)in alleviating PMOP-related pain.However,bibliometric analyses examining collaboration,development trends,and research frontiers in the field of ET for PMOP pain remain scarce.AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade.METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection.Utilizing the capabilities of CiteSpace 6.2.R5,we conducted a thorough analysis of publications,authors,frequently cited scholars,contributing nations,institutions,journals of significant citation,comprehensive references,and pivotal keywords.Additionally,our examination explored keyword cooccurrences,detailed timelines,and periods of heightened citation activity.This comprehensive search,from 2014 through 2023,was completed within a single day,on October 11,2023.RESULTS In total,2914 articles were ultimately included in the analysis.There was a rapid increase in annual publication output in 2015,followed by stable growth in subsequent years.Boninger,Michael L,is the most prolific author,whereas Ware JE has the most citations.The United States’global influence is significant,surpassing all other nations.The University of California System and Harvard University are the most influential academic institutions.J Bone Joint Surg Am is the most influential journal in this field.“Spinal cord injury”is the keyword that has garnered the most attention from researchers.The developmental pattern in this field is characterized by interdisciplinary fusion,with different disciplines converging to drive progress.CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized.Clinical management and rehabilitation strategies,along with the mechanisms underlying the relationship between ET and bone resorption analgesia,continue to be the current and future focal points of research in this field.
文摘Osteoporosis is a disease that decreases bone mass and increases bone porosity, weakening bones. The Paleo diet is an eating plan that imitates the dietary patterns of the Stone Age. It excludes grains, dairy, and processed foods and emphasizes feeding on lean meats, fruits, vegetables, and nuts. Consumption of the Paleo diet has many positive sides, such as high protein intake and weight loss. Still, excluding dairy products risks calcium and vitamin D deficiencies, which are crucial for bone health. Statistics and simulations that have explored the relationship between the Paleo diet and bone health (especially for people suffering from low bone density) show mixed outcomes on bone health.). While the consumer does get lots of benefits from fruit and vegetable intake in a large sum due to them containing nutrients like magnesium, potassium, and vitamin K (which are also necessary for bone health), the lack of dairy products (gives the maximum amount of calcium and vitamin D) raises concerns about maintaining adequate bone mineral density (BMD). More information on this topic shows the negative impact of this diet on people suffering from osteoporosis due to a lack of nutrient intake that nourishes the bone. Although the Paleo diet can enhance overall health through nutrient-dense foods and reduced processed intake, it can’t be said the same for people suffering from osteoporosis.
基金Supported by the National Natural Science Foundation of China,No.81471094 and No.82202743.
文摘BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.
基金National Natural Science Foundation of China(81960877).
文摘Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.
基金supported by the Project of State Administration of Traditional Chinese Medicine of Sichuan Province of China (No.2021MS407).
文摘Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions:Our study investigated that HHML treatment with OP promotes bone formation possibly through activation of the PI3K/Akt signaling pathway and may involve STAT3 and TP53 target interactions.
文摘Objective:To investigate and thoroughly understand the physical examination results of retired employees from a certain unit in Beijing,analyze their bone mineral density(BMD),and identify risk factors that may indicate osteoporosis.This provides a reference for the individualized prevention,identification,and control of osteoporosis among retired employees.Methods:The bone mineral density and potential factors of 148 retired employees from a unit in 2023 were analyzed and categorized into osteoporosis and non-osteoporosis groups.Key factors from the physical examinations of the two groups were compared.Spearman’s correlation analysis was used to determine the correlation between key factors and osteoporosis.Significant key factors were included in a regression analysis.A multivariate binary logistics regression was employed to identify risk factors indicative of osteoporosis.Results:Correlation analysis revealed that gender,age,and ECG ST-segment length were significantly associated with osteoporosis.Regression analysis showed that for each additional year of age,the likelihood of developing osteoporosis increased by 1.058 times;females were 2.865 times more likely to develop osteoporosis compared to males;the longer the ECG ST-segment,the higher the likelihood of osteoporosis.Conclusion:Gender,age,and ECG ST-segment length are significantly associated with osteoporosis.These indicators can provide reference points for early identification,early intervention,and reducing the incidence of osteoporosis in clinical settings.
基金This study was supported by the National Natural Science Foundation of China(Grant numbers 11932014,12372315 and 32301089)the Sichuan Science and Technology Program(Grant numbers 2022NSFSC0765 and 2022ZYD0079).
文摘Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.
基金the National Natural Science Foundation of China (Grants 82170844 and 82270613)the Sichuan Science and Technology Program (Grants 2022YFH0045 and 2022YFH0102)+5 种基金the 111 Project (Grant B18035)the 1·3·5 project for Disciplines of Excellence at West China Hospital, Sichuan University (Grant ZYGD22007 and ZYJC21004)Ningbo Top Medical and Health Research Program (No.2023030514)Ningbo Medical and Health Brand Discipline (Grant No.PPXK2018–02)Ningbo Clinical Research Center for Otolaryngology Head and Neck Disease (Grant No.2022L005)the Ministry of Education, Singapore, (Grant MOE-000395-00) to LYC.
文摘Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.
基金supported by the National Natural Science Foundation of China (81921002,81900970,82130027)Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.
基金National Natural Science Foundation of China 82172233(X.Y.)Shanghai Baoshan District Science and Technology Commission medical health project 21-E-52(B.F.).
文摘Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite thedevelopment of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their lowbioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. Thiscalls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybridstructures with bioactive components and stable fluffy topological morphology by cross-linking calcium andphosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequentgrafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealedthat these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecularmechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that smalldoseAL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivoresults restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as theconsequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant withpeculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well asbone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies forother bone diseases.
文摘Objective:To estimate the bone protective effect of alpinumisoflavone,a natural prenylated isoflavonoid,against glucocorticoid-induced osteoporosis in rats.Methods:Male Wistar rats received intramuscular administration of dexamethasone(4 mg/mL)at a dose level of 7 mg/kg for 5 weeks,and then alpinumisoflavone(5,10,and 15 mg/kg)and alendronate(2 mg/kg)from 2 weeks.The body weight and organ weight(femoral,vagina,and uterus)were estimated.MicroCT analysis,bone turnover markers,bone parameters,oxidative stress parameters,and inflammatory cytokines were estimated.mRNA expressions of related genes were also estimated.Results:Alpinumisoflavone remarkably boosted body weight and organ weight(ureters and vagina),improved microCT analysis parameters,and boosted levels of bone markers.Besides,alpinumisoflavone considerably(P<0.001)restored the level of bone turnover markers and oxidative stress parameters,remarkably suppressed the level of cytokines such as interleukin-1β,interleukin-6,tumor necrosis factor-α,and increased transforming growth factor-βand insulin-like growth factor.It also significantly restored the osteoprotegerin(OPG,RANKL,and OPG/RANKL ratio)levels and the mRNA expression of Caspase(3,6,7,9),BMPs,OPN,ALP,RUNX2,and OCN.Conclusions:The current result suggests the bone protective effect of alpinumisoflavone against glucocorticoid-induced osteoporosis in rats.
基金supported by the Integrated Project of Major Research Plan of the National Natural Science Foundation of China(No.92249303)National Natural Science Foundation of China(Nos.82371603,82230071,82102217)+3 种基金Shanghai Committee of Science and Technology Laboratory Animal Research Project(No.23141900600)Science and Technology Commission of Shanghai Municipality(21YF1413100)Shanghai Hospital Development Center(SHDC2023CRT013)Baoshan District Health Commission Talents(Excellent Academic Leaders)Program(BSWSYX-2024-05).
文摘Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Physical Activity in Osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic characteristics.Bone mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort.Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong community.Based on their PA level,participants were categorized as inactive,moderately active,or very active.Men showed higher physical exercise levels than women across the activity groups.BMD was significantly higher in the very active group than in the moderately active and inactive groups.Individuals aged>50 years are at a higher risk of developing OP and osteopenia.Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
文摘Introduction: Computed tomography (CT) measurements of bone mineral attenuation may be a useful means to identify older women who should be prioritized for bone mineral density screening. Methods: We compared bone mineral attenuation as measured in the L1 vertebra of CT studies to the results of dual-energy x-ray absorptiometry (DEXA) studies to determine what CT attenuation thresholds might yield a reasonable combination of sensitivity and specificity for the detection of osteoporosis. The study was limited to women between the ages of 65 and 75 years who had a DEXA study and a CT that included the L1 or adjacent vertebra performed within 3 years of the DEXA study. Results: There were 1226 women in this study, of whom 452 (38%) had osteoporosis based on a T-score ≤ −2.5 by DEXA. There were 830 CT studies performed with contrast and 396 studies which were performed without contrast. There was a statistically significant difference in the mean HU of those studies performed without contrast compared to those with contrast (unenhanced mean 103 HU versus 125 HU, p < 0.001). Different CT attenuation thresholds provided the most appropriate combination of sensitivity and specificity for the detection of osteoporosis when comparing CT studies performed without or with IV contrast and when all the CT data were used in aggregate. Conclusion: Different thresholds appear necessary when using the mean CT vertebral attenuation to identify older women for preferential referral for DEXA studies.
