BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the ...BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.展开更多
The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal,playing a crucial role in various physiological functions.These microbes generally live in harmony with the host;however,...The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal,playing a crucial role in various physiological functions.These microbes generally live in harmony with the host;however,when dysbiosis occurs,it can contribute to the pathogenesis of diseases,including osteoporosis.Osteoporosis,a systemic skeletal disease characterized by reduced bone mass and increased fracture risk,has attracted significant research attention concerning the role of gut microbes in its development.Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation,modulation of the gut-brain axis,and regulation of the intestinal barrier and nutrient absorption.These microbes can enhance bone mass by inhibiting osteoclast differentiation,inducing apoptosis,reducing bone resorption,and promoting osteoblast proliferation and maturation.Despite these promising findings,the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation.Notably,gut microbiota has been increasingly studied for their potential in early diagnosis,intervention,and as an adjunct therapy for osteoporosis,suggesting a growing utility in improving bone health.Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.展开更多
Xiao et al reported on the natural product sinomenine(SIN),which is a traditional Chinese medicine for treating osteoporosis via its modulation of autophagy;however,SIN was dissolved in dimethyl sulfoxide prior to adm...Xiao et al reported on the natural product sinomenine(SIN),which is a traditional Chinese medicine for treating osteoporosis via its modulation of autophagy;however,SIN was dissolved in dimethyl sulfoxide prior to administration,which is not conducive to the development of clinical injectables.By comparing solubilization techniques,including amorphisation,emulsification,micellisation,nanocrystallisation and host-vip inclusion,we found that the solubilization of SIN by host-vip inclusion can enhance solubility and improve stability and has an increased release rate and enhanced bioavailability.Therefore,we conclude that host-vip inclusion holds promise for SIN solubilization.To solubilise SIN,we selectedβ-cyclodextrin as the host agent considering its excellent biocompatibility,efficient encapsulation ability,mature preparation process and adequate drug stability.If the prerequisites of SIN-β-cyclodextrin complexes in terms of safety,efficacy,stability and the relevant laws and regulations are met,its clinical application for the treatment of osteoporosis may be achieved.展开更多
Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis ...Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis for thousands of years,but its active substance remains to be unknown.Prompted by the efforts to modernize TCM,the present study focused on the novel active substance of Lycium barbarum L.to reinforce kidney essence to produce bone marrow.Illumina deep sequencing analysis and stemloop polymerase chain reaction(PCR)assay revealed that miR162a,a Lycium barbarum L.-derived microRNA,can pass through the gastrointestinal tract to target the bone marrow in mice.Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1(SIDT1)in the stomach.Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor(NcoR).Alizarin red staining and micro-computed tomography(microCT)confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells,zebrafish,and a mouse model of osteoporosis.In addition,transgenic Nicotiana benthamiana(N.benthamiana)leaves overexpressing miR162a were developed by agrobacterium infiltration method.microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N.benthamiana leaves effectively protected against osteoporosis in mice.Our study mechanistically explains how Lycium barbarum L.improves osteoporosis and supports that Lycium barbarum L.reinforces kidney essence,thereby strengthening the bone.miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.展开更多
BACKGROUND Chronic obstructive pulmonary disease(COPD)is a progressive respiratory condition often associated with a high incidence of osteoporosis.Studies indicate that patients with COPD present with a significant d...BACKGROUND Chronic obstructive pulmonary disease(COPD)is a progressive respiratory condition often associated with a high incidence of osteoporosis.Studies indicate that patients with COPD present with a significant decrease in bone mineral density(BMD),potentially related to inflammation and corticosteroid use.AIM To investigate the relationship between BMD and lung function,mainly the forced expiratory volume in the forced expiratory volume in 1 second(FEV1)/forced vital capacity percentage(FVC%),in patients with COPD using quantitative computed tomography(QCT).METHODS This prospective cross-sectional study included 85 patients with COPD treated at Gansu Provincial People's Hospital.Exposure variables included lung function parameter(FEV1/FVC%),age,sex,body mass index,smoking status,tea-drinking habits,and physical activity.BMD was measured using QCT.Linear regression and generalized additive models were employed to analyze the relationship between exposure variables and BMD.RESULTS Linear regression analysis revealed a significant positive relationship between BMD and FEV1/FVC%(β=0.1,95%confidence interval[CI]:0.1-0.1;P<0.0001).Non-linear analysis identified a unique BMD breakpoint of 128.08 mg/cm³.Before the breakpoint,BMD was significantly positively correlated with FEV1/FVC%(β=0.245;P=0.0019);while after the breakpoint,the relationship was negative and showed no statistical significance(β=-0.136;P=0.0753).This finding underscores the critical role of BMD in COPD management and highlights the importance of individualized clinical interventions in improvement of lung function and overall health status in patients.CONCLUSION There is a complex non-linear relationship between BMD and lung function in patients with COPD,highlighting the importance of monitoring change in bone density during the management of COPD.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
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
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
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
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
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
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
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
Objective Because of the limited number of studies and small sample sizes,whether metabolic syndrome(MS)leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further in...Objective Because of the limited number of studies and small sample sizes,whether metabolic syndrome(MS)leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further investigation.This study aimed to investigate the association between MS and osteoporosis,along with its influencing factors.Methods This observational cross-sectional study included 139,470 individuals aged≥18 years who underwent health examinations from September 2014 to March 2022.Based on bone mineral density(BMD)screening results,the participants were categorized into a suspected osteoporosis or non-osteoporosis group(control).Participants were further divided into those who met 0 MS criteria,1 MS criterion,2 MS criteria,and≥3 MS criteria(MS group).Participants who had undergone health examinations at least twice formed the follow-up cohort;a self-matched analysis was performed on those with follow-up periods≥5 years and unchanged MS grouping.Results Several examination indicators in the suspected osteoporosis group showed statistically significant differences compared with the control group.The proportion of suspected osteoporosis in the MS group was significantly increased compared with that in the 0 MS criteria group(odds ratio[OR]:1.215,Z=29.11,P<0.001,95%confidence interval:1.199-1.231).After adjusting for age,sex,smoking,and alcohol consumption,the 2 MS criteria group and MS group still had OR values>1(P<0.001).In the follow-up cohort,the proportion of suspected osteoporosis increased gradually with an increase in the number of MS criteria met at baseline and during each follow-up visit(P<0.05),with the highest proportion observed in the MS group.However,the proportion of suspected osteoporosis did not increase significantly over time in the different MS groups(P>0.05).In the follow-up cohort,the proportion of individuals transitioning from normal BMD to suspected osteoporosis was higher in the MS group after≥5 years of follow-up compared with the group meeting 0 MS criteria(0.08%versus 1.15%,χ^(2)=10.76,P=0.001).There was no significant difference in BMD values for the 0 MS criteria group after 5 years(P>0.05),whereas the other three groups experienced a significant decrease in BMD values after 5 years(P<0.05).Conclusion MS is an independent risk factor for osteoporosis,and the effect of risk factors related to MS on osteoporosis may exceed that of aging alone.The specific mechanisms warrant further investigation.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 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
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
Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herb...Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.展开更多
文摘BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.
文摘The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal,playing a crucial role in various physiological functions.These microbes generally live in harmony with the host;however,when dysbiosis occurs,it can contribute to the pathogenesis of diseases,including osteoporosis.Osteoporosis,a systemic skeletal disease characterized by reduced bone mass and increased fracture risk,has attracted significant research attention concerning the role of gut microbes in its development.Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation,modulation of the gut-brain axis,and regulation of the intestinal barrier and nutrient absorption.These microbes can enhance bone mass by inhibiting osteoclast differentiation,inducing apoptosis,reducing bone resorption,and promoting osteoblast proliferation and maturation.Despite these promising findings,the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation.Notably,gut microbiota has been increasingly studied for their potential in early diagnosis,intervention,and as an adjunct therapy for osteoporosis,suggesting a growing utility in improving bone health.Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.
基金Supported by Guangdong Basic and Applied Basic Research Foundation,No.2024A1515011236General Program of Administration of Traditional Chinese Medicine of Guangdong Province,No.20241071.
文摘Xiao et al reported on the natural product sinomenine(SIN),which is a traditional Chinese medicine for treating osteoporosis via its modulation of autophagy;however,SIN was dissolved in dimethyl sulfoxide prior to administration,which is not conducive to the development of clinical injectables.By comparing solubilization techniques,including amorphisation,emulsification,micellisation,nanocrystallisation and host-vip inclusion,we found that the solubilization of SIN by host-vip inclusion can enhance solubility and improve stability and has an increased release rate and enhanced bioavailability.Therefore,we conclude that host-vip inclusion holds promise for SIN solubilization.To solubilise SIN,we selectedβ-cyclodextrin as the host agent considering its excellent biocompatibility,efficient encapsulation ability,mature preparation process and adequate drug stability.If the prerequisites of SIN-β-cyclodextrin complexes in terms of safety,efficacy,stability and the relevant laws and regulations are met,its clinical application for the treatment of osteoporosis may be achieved.
基金supported by Key Project of Jiangsu Province’s Administration of Traditional Chinese Medicine(ZD202203)Jiangsu Province’s Innovation Program(JSSCTD202142)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(traditional Chinese medicine).
文摘Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis for thousands of years,but its active substance remains to be unknown.Prompted by the efforts to modernize TCM,the present study focused on the novel active substance of Lycium barbarum L.to reinforce kidney essence to produce bone marrow.Illumina deep sequencing analysis and stemloop polymerase chain reaction(PCR)assay revealed that miR162a,a Lycium barbarum L.-derived microRNA,can pass through the gastrointestinal tract to target the bone marrow in mice.Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1(SIDT1)in the stomach.Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor(NcoR).Alizarin red staining and micro-computed tomography(microCT)confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells,zebrafish,and a mouse model of osteoporosis.In addition,transgenic Nicotiana benthamiana(N.benthamiana)leaves overexpressing miR162a were developed by agrobacterium infiltration method.microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N.benthamiana leaves effectively protected against osteoporosis in mice.Our study mechanistically explains how Lycium barbarum L.improves osteoporosis and supports that Lycium barbarum L.reinforces kidney essence,thereby strengthening the bone.miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.
基金Supported by National Natural Science Foundation of China(NSFC)of China,No.82360358Internal Medicine Research Project of Gansu Provincial People's Hospital,No.22GSSYD-77Natural Science Foundation of Gansu Province,No.22JR5RA659.
文摘BACKGROUND Chronic obstructive pulmonary disease(COPD)is a progressive respiratory condition often associated with a high incidence of osteoporosis.Studies indicate that patients with COPD present with a significant decrease in bone mineral density(BMD),potentially related to inflammation and corticosteroid use.AIM To investigate the relationship between BMD and lung function,mainly the forced expiratory volume in the forced expiratory volume in 1 second(FEV1)/forced vital capacity percentage(FVC%),in patients with COPD using quantitative computed tomography(QCT).METHODS This prospective cross-sectional study included 85 patients with COPD treated at Gansu Provincial People's Hospital.Exposure variables included lung function parameter(FEV1/FVC%),age,sex,body mass index,smoking status,tea-drinking habits,and physical activity.BMD was measured using QCT.Linear regression and generalized additive models were employed to analyze the relationship between exposure variables and BMD.RESULTS Linear regression analysis revealed a significant positive relationship between BMD and FEV1/FVC%(β=0.1,95%confidence interval[CI]:0.1-0.1;P<0.0001).Non-linear analysis identified a unique BMD breakpoint of 128.08 mg/cm³.Before the breakpoint,BMD was significantly positively correlated with FEV1/FVC%(β=0.245;P=0.0019);while after the breakpoint,the relationship was negative and showed no statistical significance(β=-0.136;P=0.0753).This finding underscores the critical role of BMD in COPD management and highlights the importance of individualized clinical interventions in improvement of lung function and overall health status in patients.CONCLUSION There is a complex non-linear relationship between BMD and lung function in patients with COPD,highlighting the importance of monitoring change in bone density during the management of COPD.
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.
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This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
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 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.
文摘Objective Because of the limited number of studies and small sample sizes,whether metabolic syndrome(MS)leads to the occurrence and progression of osteoporosis and the possible underlying mechanisms require further investigation.This study aimed to investigate the association between MS and osteoporosis,along with its influencing factors.Methods This observational cross-sectional study included 139,470 individuals aged≥18 years who underwent health examinations from September 2014 to March 2022.Based on bone mineral density(BMD)screening results,the participants were categorized into a suspected osteoporosis or non-osteoporosis group(control).Participants were further divided into those who met 0 MS criteria,1 MS criterion,2 MS criteria,and≥3 MS criteria(MS group).Participants who had undergone health examinations at least twice formed the follow-up cohort;a self-matched analysis was performed on those with follow-up periods≥5 years and unchanged MS grouping.Results Several examination indicators in the suspected osteoporosis group showed statistically significant differences compared with the control group.The proportion of suspected osteoporosis in the MS group was significantly increased compared with that in the 0 MS criteria group(odds ratio[OR]:1.215,Z=29.11,P<0.001,95%confidence interval:1.199-1.231).After adjusting for age,sex,smoking,and alcohol consumption,the 2 MS criteria group and MS group still had OR values>1(P<0.001).In the follow-up cohort,the proportion of suspected osteoporosis increased gradually with an increase in the number of MS criteria met at baseline and during each follow-up visit(P<0.05),with the highest proportion observed in the MS group.However,the proportion of suspected osteoporosis did not increase significantly over time in the different MS groups(P>0.05).In the follow-up cohort,the proportion of individuals transitioning from normal BMD to suspected osteoporosis was higher in the MS group after≥5 years of follow-up compared with the group meeting 0 MS criteria(0.08%versus 1.15%,χ^(2)=10.76,P=0.001).There was no significant difference in BMD values for the 0 MS criteria group after 5 years(P>0.05),whereas the other three groups experienced a significant decrease in BMD values after 5 years(P<0.05).Conclusion MS is an independent risk factor for osteoporosis,and the effect of risk factors related to MS on osteoporosis may exceed that of aging alone.The specific mechanisms warrant further investigation.
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.
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.
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 Natural Science Foundation of Guangdong Province(2021A1515010648)the National Natural Science Foundation of China(81903616)+1 种基金The Hong Kong Polytechnic University Start-up Funding(A0038607)The Mainland-Hong Kong Joint Funding Scheme(ITFMOST:MHX/002/20).
文摘Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.
