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
BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary...BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.展开更多
Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)...Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.展开更多
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
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
Depression is highly prevalent among postmenopausal women with osteoporosis,driven by the combined effects of hormonal changes,reduced bone density,and psychosocial stress.A recent study by Cui and Su reported that 73...Depression is highly prevalent among postmenopausal women with osteoporosis,driven by the combined effects of hormonal changes,reduced bone density,and psychosocial stress.A recent study by Cui and Su reported that 73.3%of affected women exhibited depressive symptoms,with low bone mineral density,chronic comorbidities,and reduced serotonin(5-hydroxytryptamine)levels as key risk factors.Notably,nurse-led psychological interventions improved both mood and quality of life.This editorial underscore the need to integrate mental health support into standard osteoporosis care.Simple,scalable strategies such as routine screening and nurse-delivered emotional support may help bridge the gap between physical and psychological health.These approaches are especially relevant for aging populations across diverse healthcare settings.A dual focus on bone and emotional well-being is essential to improving outcomes in this vulnerable group.展开更多
Background:Over the past 15 years,research has emphasized the crucial role of the gut microbiota in metabolism and its potential association with osteoporosis.Given the increasing interest in this area,a bibliometric ...Background:Over the past 15 years,research has emphasized the crucial role of the gut microbiota in metabolism and its potential association with osteoporosis.Given the increasing interest in this area,a bibliometric analysis is essential to comprehensively understand the field.Methods:Literature published between 2009 and 2023 was retrieved from the Web of Science.CiteSpace,a tool for visual analysis,was employed to examine various aspects of the research,including the annual number of publications,contributing institutions,journals,authors,keywords,clusters,hotspots,and emerging frontiers.Results:The analysis included 1,075 articles from 80 countries,283 institutions,and 155 authors,reflecting the rapid growth of research in this field.PEOPLES R CHINA emerged as the most productive country,while the University of California System was the most active institution.Parameswaran,Narayanan had the highest number of publications,and LI JY and OHLSSON C were the most cited authors.Key keywords such as“gut microbiota,”“bone loss,”“bone mineral density,”“inflammation,”and“health”were identified,and keywords with strong citation bursts like“in vitro,”“inflammatory bowel disease,”and“bone mineral density”indicated emerging trends.Conclusion:This bibliometric analysis successfully identified research trends and hotspots,including the fecal microbiome,musculoskeletal studies,and postmenopausal women.Continued research in these areas will enhance our understanding of osteoporosis and may lead to the development of new treatments.The findings offer valuable insights for scholars aiming to conduct in-depth research in this field.展开更多
Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We...Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We performed a cohort study of176150 community-dwelling older adults aged≥65 years and free of cognitive impairment between 2018 and 2022 using integrated healthcare data from Shenzhen,China.Diagnoses of osteoporosis,osteoporotic fractures,and dementia were identified through linked outpatient and inpatient medical records and death registration records.Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios(HRs)and 95%confidence intervals(CIs)of incident dementia associated with osteoporosis and osteoporotic fractures.The mean(SD)age of the total study population was 70.7(5.4)years,and 9605 had a previous diagnosis of osteoporosis.Over a median follow-up of 2.2(IQR:1.8–4.3,maximum:5.5)years,corresponding to 505423person-years at risk,1367 incident all-cause dementia cases,including 617 Alzheimer's disease and 298 vascular dementia cases,occurred.Physician-diagnosed osteoporosis was associated with a higher risk of all-cause dementia(HR:1.80,95%CI:1.53–2.12).The increased dementia risk tended to be more prominent among patients with osteoporotic fractures(HR:2.43,95%CI:1.83–3.23)than those without(HR:1.63,95%CI:1.35–1.97).Results were similar for Alzheimer's disease and vascular dementia.This study provides evidence that older adults with osteoporosis,especially those with osteoporotic fractures,have an elevated risk of incident dementia.Effective prevention and management of osteoporosis among the older population may be promising to mitigate the dual burden of osteoporosis and dementia.展开更多
Icariin is a natural product that possesses numerous pharmaceutical properties.Thus,this study aimed to investigate the molecular mechanism by which icariin prevents ferroptosis in aged-related osteoporosis.Firstly,mR...Icariin is a natural product that possesses numerous pharmaceutical properties.Thus,this study aimed to investigate the molecular mechanism by which icariin prevents ferroptosis in aged-related osteoporosis.Firstly,mRNA transcriptomics was used to analyze differentially expressed genes and ferroptosis markers.Next,a weighted correlation network analysis was conducted on these genes.Then,common genes among ferroptosis,Yinyanghuo,and differentially expressed genes were identified as target genes.Single-cell and spatial transcriptomics were analyzed to evaluate expression changes of target genes in bone marrow.Furthermore,to validate the results of bioinformatics analysis,MC3T3-E1 cells were used to model the preventive effects of icariin in vitro,and ferroptosis markers and mitochondrial function were both examined.In vivo,4-month-old mice were fed a diet containing icariin for 14 months,following which bone proteomics was assessed to identify essential proteins.Hematoxylin-eosin staining and immunohistochemistry assays were performed on mouse femurs.Finally,Western blot and polymerase chain reaction(PCR)analyses were performed to analyze the effects of icariin on ferroptosis target biomarkers.Ptgs2 and Hmox1 were identified as target genes related to both icariin and ferroptosis.The expression of ferroptosis-related genes was up-regulated with age.Moreover,single-cell and spatial transcriptomics analyses revealed that up-regulation of these two genes inhibited osteogenic capability.The results of the in vitro experiments indicated that icariin mitigated the accumulation of reactive oxygen species and β-galactosidase.Similarly,icariin prevented aberrant changes in the levels of ferroptosis-related proteins,consistent with the results of the in vivo experiments.Specifically,10 mg/(kg·day)of icariin inhibited ferroptosis and osteoporosis in aged mice.Overall,this study revealed that icariin could serve as a dietary supplement to prevent age-induced osteoporosis.Furthermore,Ptgs2 and Hmox1 were identified as ferroptosis-related targets through which icariin exerts its protective effects.展开更多
BACKGROUND Postmenopausal women with osteoporosis are at high risk of developing depre-ssive symptoms,necessitating specialized psychological nursing interventions.AIM To investigate factors influencing depressive sym...BACKGROUND Postmenopausal women with osteoporosis are at high risk of developing depre-ssive symptoms,necessitating specialized psychological nursing interventions.AIM To investigate factors influencing depressive symptoms in postmenopausal women with osteoporosis and develop targeted psychological nursing interven-tions.METHODS A total of 180 postmenopausal women with osteoporosis admitted to the Depar-tment of Orthopedics at the First Affiliated Hospital of Soochow University between October 2021 and October 2024 were selected as research participants.Information on age,duration of menopause,body mass index,education level,marital status,activity intensity,bone density,presence of chronic diseases,calcium supplement intake,sex hormone levels,and depressive symptoms were collected.The 24-item Hamilton Depression Scale was used for assessment.RESULTS Forty-eight patients had no depressive symptoms,and 132 patients had depre-ssive symptoms.Comprehensive univariate and multivariate logistic regression analyses showed that low bone density in the lumbar spine(L2-L4)and femoral neck,presence of chronic diseases,and low 5-hydroxytryptamine levels were independent risk factors for depressive symptoms,whereas calcium supplement intake and moderate to high-intensity activity were independent protective factors.CONCLUSION By implementing specialized psychological nursing interventions,and providing rehabilitation guidance,the incidence of depressive symptoms can be effectively reduced,improving the psychological health status and patient quality of life.展开更多
Objective:To analyze the risk of osteoporosis among middle-aged men in the cold regions of China(Heilongjiang Province)and provide theoretical support for the early identification of high-risk populations.Methods:Bone...Objective:To analyze the risk of osteoporosis among middle-aged men in the cold regions of China(Heilongjiang Province)and provide theoretical support for the early identification of high-risk populations.Methods:Bone mineral density(BMD)data were collected from male subjects aged 50-65 who met the inclusion criteria at the physical examination center of a hospital in Harbin between August to December 2022.General clinical data and dietary information were obtained through face-to-face interviews using a dietary questionnaire survey.Results:The prevalence of osteoporosis and osteopenia was 14.38%and 52.06%,respectively,while normal bone mass accounted for 33.56%.Significant differences were observed among groups in smoking habits,sunlight exposure,exercise levels,and dietary patterns at each bone mass level.The BMD of the lumbar spine,femoral neck,and hip showed a negative correlation with the Dietary Inflammatory Index(DII)score.Multivariate logistic regression analysis revealed that smoking and a diet high in oil and salt were positively associated with the risk of osteoporosis.A pro-inflammatory diet was also positively correlated with osteoporosis risk,with individuals in this group being 7.723 times more likely to develop osteoporosis compared to those in the anti-inflammatory diet group.Conclusion:The high prevalence of osteoporosis and osteopenia observed in this study highlighted that osteoporosis is a significant and pressing issue among middle-aged men.Smoking,limited sunlight exposure,reduced physical activity,diets high in oil and salt,and pro-inflammatory diets were identified as major risk factors for bone loss.These factors are closely linked to the geography,climate,and cultural practices of cold regions in China.Primary healthcare in this region should focus on the screening and prevention of osteoporosis in middle-aged men by promoting smoking cessation,increased sunlight exposure,adequate vitamin D supplementation,regular physical activity,and adherence to a healthy diet to maintain bone health.展开更多
Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metaboli...Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.展开更多
BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cau...BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cause of chronic kidney disease and end-stage kidney disease.Patients with DN often experience complex metabolic disorders and chronic inflammatory states,which not only accelerate the decline of renal function but are also closely related to complications such as cardiovascular events and osteoporosis(OP),seriously compromising quality of life.With the in-depth research on the gut microbiota and the emergence of concepts such as the"gut-kidney axis"and the"enteric-bone axis",the key roles of the gut microbiota and its metabolites in metabolic disorders,inflammatory responses,and target organ damage have been increasingly recognized.However,the specific role of gut microbiota in the pathogenesis of DN remains to be further explored.The results obtained may provide evidence to better understand the pathogenesis of DN and to identify high-risk populations at an early stage.This research direction is of strategic significance.AIM To assess the correlation of the gut microbiota metabolite trimethylamine N-oxide(TMAO)with inflammatory marker levels and OP in patients with DN.METHODS A total of 115 patients diagnosed with type 2 DN and treated at the Department of Endocrinology,Second Affiliated Hospital of Shandong First Medical University from August 2022 to December 2024 were enrolled in the DN group,and 115 patients with T2DM without nephropathy were included in the T2DM group.The two groups were compared in terms of gastrointestinal microbiota abundance and relative abundance at the genus level;levels of TMAO,inflammatory markers[including C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)],and bone metabolism markers[including procollagen type I N-terminal propeptide(PINP),β-CrossLaps(β-CTX),and alkaline phosphatase(ALP)];and lumbar spine and hip bone mineral density(BMD).The correlation of TMAO level with inflammatory factor and bone metabolism indicator levels was further analyzed.RESULTS The DN group had higher Chao1 and Simpson indices of gastrointestinal microbiota diversity than the T2DM group,whereas the ACE and Shannon indices were lower(P<0.05).The relative abundance of Firmicutes was higher,and the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria were lower in the DN group than in the T2DM group(P<0.05).CRP,IL-6,IL-8,TNF-α,and TMAO levels were considerably elevated in the DN group compared to the T2DM group(P<0.05).Moreover,the DN group had higher levels of bone turnover markers-including PINP,β-CTX,and ALP-but lower lumbar spine and hip BMDs than the T2DM group(P<0.05).TMAO level positively correlated with the Chao1 and Simpson indices and negatively correlated with the ACE and Shannon indices of gut microbiota diversity.TMAO level also negatively correlated with the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria and positively correlated with the abundance of Firmicutes.Additionally,TMAO level positively correlated with the inflammatory markers CRP,IL-6,IL-8,and TNF-α,as well as with the bone turnover markers PINP,β-CTX,and ALP.It negatively correlated with lumbar spine and hip BMDs(P<0.05).CONCLUSION Inflammatory and bone metabolic levels in patients with DN were found to be associated with the gut microbiota–derived metabolite TMAO.Elevated TMAO levels may mediate inflammatory responses and bone metabolism disorders in patients with DN,thereby contributing to the progression of systemic inflammation and OP.展开更多
The World Health Organization has declared that COVID-19 no longer constitutes a“public health emergency of international concern,”yet the long-term impact of SARSCoV-2 infection on bone health continues to pose new...The World Health Organization has declared that COVID-19 no longer constitutes a“public health emergency of international concern,”yet the long-term impact of SARSCoV-2 infection on bone health continues to pose new challenges for global public health.In recent years,numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can lead to secondary osteoporosis.The mechanisms involved are related to the virus's direct effects on bone tissue,dysregulation of the body's inflammatory response,hypoxia,noncoding RNA imbalance,and metabolic abnormalities.Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis,current research is not comprehensive and in depth.Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism,elucidate the specific mechanisms of pathogenesis,and explore potential interventions.This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis,summarize the underlying mechanisms,and provide direction for future research.展开更多
BACKGROUND Acromegaly,a disease of excess growth hormone,is known to alter bone structure and increase the risk of osteoporosis and fractures.This study aimed to assess the prevalence of vertebral,non-vertebral,and hi...BACKGROUND Acromegaly,a disease of excess growth hormone,is known to alter bone structure and increase the risk of osteoporosis and fractures.This study aimed to assess the prevalence of vertebral,non-vertebral,and hip fragility fractures,as well as osteoporosis,in a cohort of patients with acromegaly.AIM To assess the prevalence of vertebral fragility fractures,non-vertebral fragility fractures,hip fragility fractures,and osteoporosis in patients diagnosed with acromegaly.METHODS Data were collected on age,sex,body mass index(BMI),time from diagnosis of acromegaly,insulin-like growth factor(IGF-1)levels,disease control,pharmacological management,risk factors for osteoporosis,vertebral fragility fractures,non-vertebral fragility fractures,hip fragility fractures,and osteoporosis.RESULTS A total of 124 patients with acromegaly were included(67 men and 57 women).The mean age at diagnosis was 44±12 years;the mean time from diagnosis was 12±8 years;and the mean BMI was 27±4 kg/m².Fragility fractures were found in 27 patients(21%).There were no significant differences in the presence of osteoporosis or fragility fractures according to age,sex,BMI,duration of acrom egaly,or IGF-1 levels at diagnosis.A higher percentage of patients with osteoporosis were treated with somatostatin analogs compared to those without osteoporosis(46%vs 15%;P<0.05).CONCLUSION A high prevalence of osteoporosis and fragility fractures was found in patients with acromegaly,regardless of age,sex,BMI,time from diagnosis,IGF-1 levels,and disease control.More patients with osteoporosis were treated with somatostatin analogs compared to those without osteoporosis.Taken together,our results suggest that the severity of the disease and the need for second-line therapies,may be associated with the increased risk of osteoporosis.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
Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activa...Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activator of nuclear factor(NF)-κB(ER/OPG/RANKL)signaling pathway.Methods Network pharmacology was employed with the databases of PubChem,BindingDB,DisGeNET,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG),along with Cytoscape 3.10.2 for identifying the targets and pathways of NNHE relevant to OP.A total of 48 specific pathogen-free(SPF)grade female Wistar rats were randomly divided into six groups(n=8 per group):sham control,OVX control,OVX+NNHE[100,200,400 mg/(kg·d)],and OVX+alendronate[3 mg/(kg·week)].The treatment lasted for 16 weeks.Post-treatment assessment included bone parameters(weight,thickness,density,volume,and length),serum biochemical markers[parathyroid hormone(PTH),estrogen,OPG,RANKL,tartrate-resistant acid phosphatase(TRAP),osteocalcin(OC),calcitonin(CT),calcium(Ca),phosphorus(P),and alkaline phosphatase(ALP)],pro-inflammatory cytokines[tumour necrosis factor(TNF)-α,NF-κB,interleukin(IL)-1β,and IL-6],lipid profiles[total cholesterol(TC),triglycerides(TG),low density lipoprotein(LDL),and high density lipoprotein(HDL)],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH),and malondialdehyde(MDA)],and histopathological analyses of femur,uterus,and vaginal tissues.Results Network pharmacology analysis revealed 61 overlapping targets between NNHE and osteoporosis-related genes,including signal transducer and activator of transcription 3(STAT3),NF-κB subunit 1(NFKB1),dopamine receptor D2(DRD2),matrix metalloproteinase 9(MMP9),and caspase-3.GO and KEGG enrichment suggested involvement in the ER/OPG/RANKL signaling pathway.In vivo studies demonstrated that NNHE treatment(400 mg/kg)significantly reduced OVX-induced body weight gain and exhibited estrogenic activity in the vaginal cornification assay.NNHE at 200 and 400 mg/kg significantly increased serum estrogen levels compared with OVX control group,while uterine weight remained unaffected.NNHE significantly improved the lipid profile compared with OVX group,with TC,TG,and LDL decreased,while HDL levels were increased at 200 and 400 mg/kg.Bone metabolism markers were significantly improved compared with OVX group,with serum Ca and P levels restored at all NNHE doses and ALP activity reduced.NNHE effectively modulated bone turnover markers compared with OVX group by reducing levels of OC,TRAP,and PTH,and increasing level of CT.In addition,NNHE decreased RANKL level while increasing OPG level at 200 and 400 mg/kg.Bone mineral density(BMD)was significantly enhanced compared with OVX group.Serum oxidative stress was significantly mitigated compared with OVX group through increased levels of antioxidant enzymes(SOD,CAT,and GSH)and reduced MDA,with the most pronounced effects observed at 400 mg/kg.Pro-inflammatory cytokines(TNF-α,IL-6,IL-1β,and NF-κB)were significantly reduced in all NNHE treatment groups compared with OVX group.Histopathological analysis confirmed restoration of trabecular bone structure and normalization of reproductive tissue morphology in OVX rats after NNHE treatment.Conclusion NNHE demonstrated significant protective effects against OVX-induced osteoporosis through ER/OPG/RANKL signaling pathway modulation,oxidative stress,and inflammation suppression,resulting in improved BMD and structural integrity.These findings indicate that NNHE may represent a promising therapeutic candidate for postmenopausal osteoporosis management and merits further clinical investigation.展开更多
Osteoporosis is a known risk factor for rotator cuff tears(RCTs),but the causal correlation and underlying mechanisms remain unclear.This study aims to evaluate the impact of osteoporosis on RCT risk and investigate t...Osteoporosis is a known risk factor for rotator cuff tears(RCTs),but the causal correlation and underlying mechanisms remain unclear.This study aims to evaluate the impact of osteoporosis on RCT risk and investigate their genetic associations.Using data from the UK Biobank(n=457871),cross-sectional analyses demonstrated that osteoporosis was significantly associated with an increased risk of RCTs(adjusted OR[95%CI]=1.38[1.25–1.52]).A longitudinal analysis of a subset of patients(n=268117)over 11 years revealed that osteoporosis increased the risk of RCTs(adjusted HR[95%CI]=1.56[1.29–1.87]),which is notably varied between sexes in sex-stratified analysis.Causal inference methods,including propensity score matching,inverse probability weighting,causal random forest and survival random forest models further confirmed the causal effect,both from cross-sectional and longitudinal perspectives.展开更多
Gut microbiota(GM)exerts an indispensable effect in human health,especially in metabolism regulation.^(1)Recent studies have identified a potential association with osteoporosis.^(2–5)At the same time,GM intervention...Gut microbiota(GM)exerts an indispensable effect in human health,especially in metabolism regulation.^(1)Recent studies have identified a potential association with osteoporosis.^(2–5)At the same time,GM intervention,such as antibiotic treatment,^(6)fecal microbiota transplantation(FMT),^(7–8)supplement of probiotics^(9–10)and other means,will also subsequently affect bone metabolism.Further,GM dysbiosis was also mentioned as one of pathophysiological mechanism of osteoporosis,even written in the clinical diagnosis and treatment guidelines^(11)[Fig.1,based on Guidelines for the diagnosis and treatment of primary osteoporosis in China(2022)].展开更多
This study investigated the intervention ability and potential mechanism of Lactobacillus helveticus-derived whey on ovariectomy(OVX)-induced osteoporosis.The whey from two L.helveticus strains,ATCC15009,and CCFM1096,...This study investigated the intervention ability and potential mechanism of Lactobacillus helveticus-derived whey on ovariectomy(OVX)-induced osteoporosis.The whey from two L.helveticus strains,ATCC15009,and CCFM1096,were orally gavaged to OVXrats at a dose of 500 mg/kg for 12 weeks.The effect of L.helveticus-derived whey on osteoporosis varied,whereas the raw milk-derived whey showed no significant effect.CCFM1096 whey significantly enhanced bone biomechanics,improved bone microstructure,upregulated bone formation markers(bone alkaline phosphatase(BALP),bone gamma-carboxyglutamic acid-containing protein(BPG)),and downregulated bone resorption markers(tartrate-resistant acid phosphatase(TRAP),C-terminal telopeptide of type I collagen(CTX-1),procollagen type I N-terminal propeptide(PINP)),leading to promotion of osteoblast formation and inhibition of osteoclast generation.CCFM1096 whey affected bile acid metabolism,restored intestinal homeostasis,and prevented osteoporosis in OVX rats,with higher concentrations of unsaturated fatty acids,orotic acid,and uridine than that of ATCC15009.These findings provide important insights for the development of functional dairy products targeting osteoporotic populations and further demonstrate the importance of starter cultures in fermented foods.展开更多
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 the Multi-center RCT Clinical Project of the National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital(NCRCGPLAGH-2023001)the Beijing Nova Program(No.20220484020)+1 种基金the Beijing Natural Science Foundation(No.7252181)the Capital’s Funds for Health Improvement and Research(No.2024-2G-5033).
文摘BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.
文摘Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
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.
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 the National Natural Science Foundation of China,No.82260873.
文摘Depression is highly prevalent among postmenopausal women with osteoporosis,driven by the combined effects of hormonal changes,reduced bone density,and psychosocial stress.A recent study by Cui and Su reported that 73.3%of affected women exhibited depressive symptoms,with low bone mineral density,chronic comorbidities,and reduced serotonin(5-hydroxytryptamine)levels as key risk factors.Notably,nurse-led psychological interventions improved both mood and quality of life.This editorial underscore the need to integrate mental health support into standard osteoporosis care.Simple,scalable strategies such as routine screening and nurse-delivered emotional support may help bridge the gap between physical and psychological health.These approaches are especially relevant for aging populations across diverse healthcare settings.A dual focus on bone and emotional well-being is essential to improving outcomes in this vulnerable group.
文摘Background:Over the past 15 years,research has emphasized the crucial role of the gut microbiota in metabolism and its potential association with osteoporosis.Given the increasing interest in this area,a bibliometric analysis is essential to comprehensively understand the field.Methods:Literature published between 2009 and 2023 was retrieved from the Web of Science.CiteSpace,a tool for visual analysis,was employed to examine various aspects of the research,including the annual number of publications,contributing institutions,journals,authors,keywords,clusters,hotspots,and emerging frontiers.Results:The analysis included 1,075 articles from 80 countries,283 institutions,and 155 authors,reflecting the rapid growth of research in this field.PEOPLES R CHINA emerged as the most productive country,while the University of California System was the most active institution.Parameswaran,Narayanan had the highest number of publications,and LI JY and OHLSSON C were the most cited authors.Key keywords such as“gut microbiota,”“bone loss,”“bone mineral density,”“inflammation,”and“health”were identified,and keywords with strong citation bursts like“in vitro,”“inflammatory bowel disease,”and“bone mineral density”indicated emerging trends.Conclusion:This bibliometric analysis successfully identified research trends and hotspots,including the fecal microbiome,musculoskeletal studies,and postmenopausal women.Continued research in these areas will enhance our understanding of osteoporosis and may lead to the development of new treatments.The findings offer valuable insights for scholars aiming to conduct in-depth research in this field.
基金supported by the Shenzhen Medical Academy of Research and Translation(Grant C2302001)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant 2023ZD0503500)+5 种基金the National Natural Science Foundation of China(Grants 82030102,12126602)the Shenzhen Science and Technology Innovation Committee(No.ZDSYS20200810171403013)the Talents enlisted in major talent programs of Guangdong Province(20210N020921)the Shenzhen Development and Reform Committee(No.XMHT20230108022)the Medical Research Innovation Project(Grant G030410001)the Shenzhen Medical Research Funds(Grant A2402041)。
文摘Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We performed a cohort study of176150 community-dwelling older adults aged≥65 years and free of cognitive impairment between 2018 and 2022 using integrated healthcare data from Shenzhen,China.Diagnoses of osteoporosis,osteoporotic fractures,and dementia were identified through linked outpatient and inpatient medical records and death registration records.Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios(HRs)and 95%confidence intervals(CIs)of incident dementia associated with osteoporosis and osteoporotic fractures.The mean(SD)age of the total study population was 70.7(5.4)years,and 9605 had a previous diagnosis of osteoporosis.Over a median follow-up of 2.2(IQR:1.8–4.3,maximum:5.5)years,corresponding to 505423person-years at risk,1367 incident all-cause dementia cases,including 617 Alzheimer's disease and 298 vascular dementia cases,occurred.Physician-diagnosed osteoporosis was associated with a higher risk of all-cause dementia(HR:1.80,95%CI:1.53–2.12).The increased dementia risk tended to be more prominent among patients with osteoporotic fractures(HR:2.43,95%CI:1.83–3.23)than those without(HR:1.63,95%CI:1.35–1.97).Results were similar for Alzheimer's disease and vascular dementia.This study provides evidence that older adults with osteoporosis,especially those with osteoporotic fractures,have an elevated risk of incident dementia.Effective prevention and management of osteoporosis among the older population may be promising to mitigate the dual burden of osteoporosis and dementia.
基金funded by the Natural Science Foundation of Hubei Province(2021CFB414)Scientific Research Program of Traditional Chinese Medicine of Hubei Provincial Health and Wellness Commission(ZY2021M074).
文摘Icariin is a natural product that possesses numerous pharmaceutical properties.Thus,this study aimed to investigate the molecular mechanism by which icariin prevents ferroptosis in aged-related osteoporosis.Firstly,mRNA transcriptomics was used to analyze differentially expressed genes and ferroptosis markers.Next,a weighted correlation network analysis was conducted on these genes.Then,common genes among ferroptosis,Yinyanghuo,and differentially expressed genes were identified as target genes.Single-cell and spatial transcriptomics were analyzed to evaluate expression changes of target genes in bone marrow.Furthermore,to validate the results of bioinformatics analysis,MC3T3-E1 cells were used to model the preventive effects of icariin in vitro,and ferroptosis markers and mitochondrial function were both examined.In vivo,4-month-old mice were fed a diet containing icariin for 14 months,following which bone proteomics was assessed to identify essential proteins.Hematoxylin-eosin staining and immunohistochemistry assays were performed on mouse femurs.Finally,Western blot and polymerase chain reaction(PCR)analyses were performed to analyze the effects of icariin on ferroptosis target biomarkers.Ptgs2 and Hmox1 were identified as target genes related to both icariin and ferroptosis.The expression of ferroptosis-related genes was up-regulated with age.Moreover,single-cell and spatial transcriptomics analyses revealed that up-regulation of these two genes inhibited osteogenic capability.The results of the in vitro experiments indicated that icariin mitigated the accumulation of reactive oxygen species and β-galactosidase.Similarly,icariin prevented aberrant changes in the levels of ferroptosis-related proteins,consistent with the results of the in vivo experiments.Specifically,10 mg/(kg·day)of icariin inhibited ferroptosis and osteoporosis in aged mice.Overall,this study revealed that icariin could serve as a dietary supplement to prevent age-induced osteoporosis.Furthermore,Ptgs2 and Hmox1 were identified as ferroptosis-related targets through which icariin exerts its protective effects.
文摘BACKGROUND Postmenopausal women with osteoporosis are at high risk of developing depre-ssive symptoms,necessitating specialized psychological nursing interventions.AIM To investigate factors influencing depressive symptoms in postmenopausal women with osteoporosis and develop targeted psychological nursing interven-tions.METHODS A total of 180 postmenopausal women with osteoporosis admitted to the Depar-tment of Orthopedics at the First Affiliated Hospital of Soochow University between October 2021 and October 2024 were selected as research participants.Information on age,duration of menopause,body mass index,education level,marital status,activity intensity,bone density,presence of chronic diseases,calcium supplement intake,sex hormone levels,and depressive symptoms were collected.The 24-item Hamilton Depression Scale was used for assessment.RESULTS Forty-eight patients had no depressive symptoms,and 132 patients had depre-ssive symptoms.Comprehensive univariate and multivariate logistic regression analyses showed that low bone density in the lumbar spine(L2-L4)and femoral neck,presence of chronic diseases,and low 5-hydroxytryptamine levels were independent risk factors for depressive symptoms,whereas calcium supplement intake and moderate to high-intensity activity were independent protective factors.CONCLUSION By implementing specialized psychological nursing interventions,and providing rehabilitation guidance,the incidence of depressive symptoms can be effectively reduced,improving the psychological health status and patient quality of life.
文摘Objective:To analyze the risk of osteoporosis among middle-aged men in the cold regions of China(Heilongjiang Province)and provide theoretical support for the early identification of high-risk populations.Methods:Bone mineral density(BMD)data were collected from male subjects aged 50-65 who met the inclusion criteria at the physical examination center of a hospital in Harbin between August to December 2022.General clinical data and dietary information were obtained through face-to-face interviews using a dietary questionnaire survey.Results:The prevalence of osteoporosis and osteopenia was 14.38%and 52.06%,respectively,while normal bone mass accounted for 33.56%.Significant differences were observed among groups in smoking habits,sunlight exposure,exercise levels,and dietary patterns at each bone mass level.The BMD of the lumbar spine,femoral neck,and hip showed a negative correlation with the Dietary Inflammatory Index(DII)score.Multivariate logistic regression analysis revealed that smoking and a diet high in oil and salt were positively associated with the risk of osteoporosis.A pro-inflammatory diet was also positively correlated with osteoporosis risk,with individuals in this group being 7.723 times more likely to develop osteoporosis compared to those in the anti-inflammatory diet group.Conclusion:The high prevalence of osteoporosis and osteopenia observed in this study highlighted that osteoporosis is a significant and pressing issue among middle-aged men.Smoking,limited sunlight exposure,reduced physical activity,diets high in oil and salt,and pro-inflammatory diets were identified as major risk factors for bone loss.These factors are closely linked to the geography,climate,and cultural practices of cold regions in China.Primary healthcare in this region should focus on the screening and prevention of osteoporosis in middle-aged men by promoting smoking cessation,increased sunlight exposure,adequate vitamin D supplementation,regular physical activity,and adherence to a healthy diet to maintain bone health.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘Diabetic osteoporosis(DOP)is a common complication in diabetes,driven by hyperglycemia-induced metabolic disturbances,chronic inflammation,and oxi-dative stress.This review describes the critical role of iron metabolism dysregu-lation in DOP pathogenesis,focusing on ferroptosis,a novel iron-dependent cell death pathway characterized by lipid peroxidation and reactive oxygen species(ROS)overproduction.Diabetic conditions exacerbate iron overload,impairing osteoblast function and enhancing osteoclast activity,while triggering ferroptosis in bone cells.Ferroptosis not only accelerates osteoblast apoptosis but also amplifies osteoclast-mediated bone resorption,synergistically promoting bone loss.Furthermore,chronic inflammation and oxidative stress disrupt the balance between bone formation and resorption,with elevated pro-inflammatory cyto-kines(e.g.,tumor necrosis factor-α,interleukin-6)and ROS exacerbating cellular dysfunction.Therapeutic strategies targeting iron metabolism(e.g.,deferoxamine)and ferroptosis inhibition(e.g.,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway activation,antioxidants like melatonin)demonstrate potential to mitigate DOP progression.Future research should prioritize personalized interventions,clinical trials of iron chelators and antioxidants,and mechanistic studies to refine therapeutic approaches.This review provides a comprehensive framework for understanding DOP pathogenesis and highlights innovative strategies to improve bone health in diabetic patients.
文摘BACKGROUND Diabetic nephropathy(DN)is one of the most serious microvascular complications of type 2 diabetes mellitus(T2DM),and its incidence increases with the global rise in diabetes prevalence.It is the leading cause of chronic kidney disease and end-stage kidney disease.Patients with DN often experience complex metabolic disorders and chronic inflammatory states,which not only accelerate the decline of renal function but are also closely related to complications such as cardiovascular events and osteoporosis(OP),seriously compromising quality of life.With the in-depth research on the gut microbiota and the emergence of concepts such as the"gut-kidney axis"and the"enteric-bone axis",the key roles of the gut microbiota and its metabolites in metabolic disorders,inflammatory responses,and target organ damage have been increasingly recognized.However,the specific role of gut microbiota in the pathogenesis of DN remains to be further explored.The results obtained may provide evidence to better understand the pathogenesis of DN and to identify high-risk populations at an early stage.This research direction is of strategic significance.AIM To assess the correlation of the gut microbiota metabolite trimethylamine N-oxide(TMAO)with inflammatory marker levels and OP in patients with DN.METHODS A total of 115 patients diagnosed with type 2 DN and treated at the Department of Endocrinology,Second Affiliated Hospital of Shandong First Medical University from August 2022 to December 2024 were enrolled in the DN group,and 115 patients with T2DM without nephropathy were included in the T2DM group.The two groups were compared in terms of gastrointestinal microbiota abundance and relative abundance at the genus level;levels of TMAO,inflammatory markers[including C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)],and bone metabolism markers[including procollagen type I N-terminal propeptide(PINP),β-CrossLaps(β-CTX),and alkaline phosphatase(ALP)];and lumbar spine and hip bone mineral density(BMD).The correlation of TMAO level with inflammatory factor and bone metabolism indicator levels was further analyzed.RESULTS The DN group had higher Chao1 and Simpson indices of gastrointestinal microbiota diversity than the T2DM group,whereas the ACE and Shannon indices were lower(P<0.05).The relative abundance of Firmicutes was higher,and the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria were lower in the DN group than in the T2DM group(P<0.05).CRP,IL-6,IL-8,TNF-α,and TMAO levels were considerably elevated in the DN group compared to the T2DM group(P<0.05).Moreover,the DN group had higher levels of bone turnover markers-including PINP,β-CTX,and ALP-but lower lumbar spine and hip BMDs than the T2DM group(P<0.05).TMAO level positively correlated with the Chao1 and Simpson indices and negatively correlated with the ACE and Shannon indices of gut microbiota diversity.TMAO level also negatively correlated with the relative abundances of Bacteroidetes,Proteobacteria,and Actinobacteria and positively correlated with the abundance of Firmicutes.Additionally,TMAO level positively correlated with the inflammatory markers CRP,IL-6,IL-8,and TNF-α,as well as with the bone turnover markers PINP,β-CTX,and ALP.It negatively correlated with lumbar spine and hip BMDs(P<0.05).CONCLUSION Inflammatory and bone metabolic levels in patients with DN were found to be associated with the gut microbiota–derived metabolite TMAO.Elevated TMAO levels may mediate inflammatory responses and bone metabolism disorders in patients with DN,thereby contributing to the progression of systemic inflammation and OP.
基金State Key Laboratory Special FundGrant/Award Number:2060204+5 种基金Key-Area Research and Development Program of Guangdong ProvinceGrant/Award Number:2022B1111020005Chinese Academy of Medical Sciences Innovation Fund for Medical SciencesGrant/Award Number:2021-I2M-1-034,2023-I2M-2-001The Foundation for Innovative Research Groups of the National Natural Science Foundation of ChinaGrant/Award Number:82221004。
文摘The World Health Organization has declared that COVID-19 no longer constitutes a“public health emergency of international concern,”yet the long-term impact of SARSCoV-2 infection on bone health continues to pose new challenges for global public health.In recent years,numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can lead to secondary osteoporosis.The mechanisms involved are related to the virus's direct effects on bone tissue,dysregulation of the body's inflammatory response,hypoxia,noncoding RNA imbalance,and metabolic abnormalities.Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis,current research is not comprehensive and in depth.Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism,elucidate the specific mechanisms of pathogenesis,and explore potential interventions.This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis,summarize the underlying mechanisms,and provide direction for future research.
文摘BACKGROUND Acromegaly,a disease of excess growth hormone,is known to alter bone structure and increase the risk of osteoporosis and fractures.This study aimed to assess the prevalence of vertebral,non-vertebral,and hip fragility fractures,as well as osteoporosis,in a cohort of patients with acromegaly.AIM To assess the prevalence of vertebral fragility fractures,non-vertebral fragility fractures,hip fragility fractures,and osteoporosis in patients diagnosed with acromegaly.METHODS Data were collected on age,sex,body mass index(BMI),time from diagnosis of acromegaly,insulin-like growth factor(IGF-1)levels,disease control,pharmacological management,risk factors for osteoporosis,vertebral fragility fractures,non-vertebral fragility fractures,hip fragility fractures,and osteoporosis.RESULTS A total of 124 patients with acromegaly were included(67 men and 57 women).The mean age at diagnosis was 44±12 years;the mean time from diagnosis was 12±8 years;and the mean BMI was 27±4 kg/m².Fragility fractures were found in 27 patients(21%).There were no significant differences in the presence of osteoporosis or fragility fractures according to age,sex,BMI,duration of acrom egaly,or IGF-1 levels at diagnosis.A higher percentage of patients with osteoporosis were treated with somatostatin analogs compared to those without osteoporosis(46%vs 15%;P<0.05).CONCLUSION A high prevalence of osteoporosis and fragility fractures was found in patients with acromegaly,regardless of age,sex,BMI,time from diagnosis,IGF-1 levels,and disease control.More patients with osteoporosis were treated with somatostatin analogs compared to those without osteoporosis.Taken together,our results suggest that the severity of the disease and the need for second-line therapies,may be associated with the increased risk of osteoporosis.
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.
文摘Objective To investigate the bone-protective potential of Nelumbo nucifera Gaertn.seed hydroalcoholic extract(NNHE)in an ovariectomized(OVX)rat model by modulating the estrogen receptor/osteoprotegerin/receptor activator of nuclear factor(NF)-κB(ER/OPG/RANKL)signaling pathway.Methods Network pharmacology was employed with the databases of PubChem,BindingDB,DisGeNET,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG),along with Cytoscape 3.10.2 for identifying the targets and pathways of NNHE relevant to OP.A total of 48 specific pathogen-free(SPF)grade female Wistar rats were randomly divided into six groups(n=8 per group):sham control,OVX control,OVX+NNHE[100,200,400 mg/(kg·d)],and OVX+alendronate[3 mg/(kg·week)].The treatment lasted for 16 weeks.Post-treatment assessment included bone parameters(weight,thickness,density,volume,and length),serum biochemical markers[parathyroid hormone(PTH),estrogen,OPG,RANKL,tartrate-resistant acid phosphatase(TRAP),osteocalcin(OC),calcitonin(CT),calcium(Ca),phosphorus(P),and alkaline phosphatase(ALP)],pro-inflammatory cytokines[tumour necrosis factor(TNF)-α,NF-κB,interleukin(IL)-1β,and IL-6],lipid profiles[total cholesterol(TC),triglycerides(TG),low density lipoprotein(LDL),and high density lipoprotein(HDL)],oxidative stress markers[superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH),and malondialdehyde(MDA)],and histopathological analyses of femur,uterus,and vaginal tissues.Results Network pharmacology analysis revealed 61 overlapping targets between NNHE and osteoporosis-related genes,including signal transducer and activator of transcription 3(STAT3),NF-κB subunit 1(NFKB1),dopamine receptor D2(DRD2),matrix metalloproteinase 9(MMP9),and caspase-3.GO and KEGG enrichment suggested involvement in the ER/OPG/RANKL signaling pathway.In vivo studies demonstrated that NNHE treatment(400 mg/kg)significantly reduced OVX-induced body weight gain and exhibited estrogenic activity in the vaginal cornification assay.NNHE at 200 and 400 mg/kg significantly increased serum estrogen levels compared with OVX control group,while uterine weight remained unaffected.NNHE significantly improved the lipid profile compared with OVX group,with TC,TG,and LDL decreased,while HDL levels were increased at 200 and 400 mg/kg.Bone metabolism markers were significantly improved compared with OVX group,with serum Ca and P levels restored at all NNHE doses and ALP activity reduced.NNHE effectively modulated bone turnover markers compared with OVX group by reducing levels of OC,TRAP,and PTH,and increasing level of CT.In addition,NNHE decreased RANKL level while increasing OPG level at 200 and 400 mg/kg.Bone mineral density(BMD)was significantly enhanced compared with OVX group.Serum oxidative stress was significantly mitigated compared with OVX group through increased levels of antioxidant enzymes(SOD,CAT,and GSH)and reduced MDA,with the most pronounced effects observed at 400 mg/kg.Pro-inflammatory cytokines(TNF-α,IL-6,IL-1β,and NF-κB)were significantly reduced in all NNHE treatment groups compared with OVX group.Histopathological analysis confirmed restoration of trabecular bone structure and normalization of reproductive tissue morphology in OVX rats after NNHE treatment.Conclusion NNHE demonstrated significant protective effects against OVX-induced osteoporosis through ER/OPG/RANKL signaling pathway modulation,oxidative stress,and inflammation suppression,resulting in improved BMD and structural integrity.These findings indicate that NNHE may represent a promising therapeutic candidate for postmenopausal osteoporosis management and merits further clinical investigation.
基金the Scientific Research Innovation Capability Support Project for Young Faculty(ZYGXQNJSKYCXNLZCXM-H8)Fundamental Research Funds for the Central Universities(2024ZYGXZR077)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2023B1515120006)Guangzhou Basic and Applied Basic Research Foundation(2024A04J5776)the Research Fund(2023QN10Y421)Guangzhou Talent Recruitment Team Program(2024D03J0004),all related to this study.
文摘Osteoporosis is a known risk factor for rotator cuff tears(RCTs),but the causal correlation and underlying mechanisms remain unclear.This study aims to evaluate the impact of osteoporosis on RCT risk and investigate their genetic associations.Using data from the UK Biobank(n=457871),cross-sectional analyses demonstrated that osteoporosis was significantly associated with an increased risk of RCTs(adjusted OR[95%CI]=1.38[1.25–1.52]).A longitudinal analysis of a subset of patients(n=268117)over 11 years revealed that osteoporosis increased the risk of RCTs(adjusted HR[95%CI]=1.56[1.29–1.87]),which is notably varied between sexes in sex-stratified analysis.Causal inference methods,including propensity score matching,inverse probability weighting,causal random forest and survival random forest models further confirmed the causal effect,both from cross-sectional and longitudinal perspectives.
基金supported by the National Key Research and Development Program(2021YFC2501700)the National Natural Science Foundation of China(82330078,82272554)Beijing Natural Science Foundation(7232214,L241067)。
文摘Gut microbiota(GM)exerts an indispensable effect in human health,especially in metabolism regulation.^(1)Recent studies have identified a potential association with osteoporosis.^(2–5)At the same time,GM intervention,such as antibiotic treatment,^(6)fecal microbiota transplantation(FMT),^(7–8)supplement of probiotics^(9–10)and other means,will also subsequently affect bone metabolism.Further,GM dysbiosis was also mentioned as one of pathophysiological mechanism of osteoporosis,even written in the clinical diagnosis and treatment guidelines^(11)[Fig.1,based on Guidelines for the diagnosis and treatment of primary osteoporosis in China(2022)].
基金supported by the National Natural Science Foundation of China(31871829,31820103010,and 32021005)the Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province(Jiangsu,China).
文摘This study investigated the intervention ability and potential mechanism of Lactobacillus helveticus-derived whey on ovariectomy(OVX)-induced osteoporosis.The whey from two L.helveticus strains,ATCC15009,and CCFM1096,were orally gavaged to OVXrats at a dose of 500 mg/kg for 12 weeks.The effect of L.helveticus-derived whey on osteoporosis varied,whereas the raw milk-derived whey showed no significant effect.CCFM1096 whey significantly enhanced bone biomechanics,improved bone microstructure,upregulated bone formation markers(bone alkaline phosphatase(BALP),bone gamma-carboxyglutamic acid-containing protein(BPG)),and downregulated bone resorption markers(tartrate-resistant acid phosphatase(TRAP),C-terminal telopeptide of type I collagen(CTX-1),procollagen type I N-terminal propeptide(PINP)),leading to promotion of osteoblast formation and inhibition of osteoclast generation.CCFM1096 whey affected bile acid metabolism,restored intestinal homeostasis,and prevented osteoporosis in OVX rats,with higher concentrations of unsaturated fatty acids,orotic acid,and uridine than that of ATCC15009.These findings provide important insights for the development of functional dairy products targeting osteoporotic populations and further demonstrate the importance of starter cultures in fermented foods.