Objective:Osteoporosis is a systemic metabolic disease characterized by decreased bone mass,deterioration of bone microstructure,and increased fracture risk.Its occurrence is closely related to sex,age,and lifestyle f...Objective:Osteoporosis is a systemic metabolic disease characterized by decreased bone mass,deterioration of bone microstructure,and increased fracture risk.Its occurrence is closely related to sex,age,and lifestyle factors.Environmental exposure to heavy metals and metalloids may also influence its development,although existing findings remain inconsistent.The sex differences in the association between mixed metal exposure and osteoporosis are still unclear.This study aims to investigate whether sex differences exist in the associations between cadmium(Cd),lead(Pb),mercury(Hg),selenium(Se),manganese(Mn),and their mixtures and osteoporosis among men aged≥50 years and postmenopausal women,and to analyze the potential moderating effect of dairy product consumption on these associations.Methods:Data from the National Health and Nutrition Examination Survey(NHANES)2013−2014 and 2017−2018 cycles were used.In men and women separately,generalized linear regression models(univariate regression analysis and multivariate logistic regression)were applied to examine the relationships between single-metal exposure and osteoporosis at the femoral neck and vertebrae.A weighted quantile sum(WQS)model was used to construct a weighted index of mixed metal exposure to quantify the joint effects of multiple metals.Bayesian kernel machine regression(BKMR)was used to systematically evaluate the associations between blood Cd,Pb,Hg,Se,Mn,and their mixtures and osteoporosis at different skeletal sites,capturing potential nonlinear relationships and interactions among metals.Participants were further stratified into high dairy consumption(≥7 times/week)and low dairy consumption(<7 times/week)groups to explore the potential moderating effect of dairy consumption on the association between Cd exposure and osteoporosis.Results:Multivariate logistic regression analysis showed that,in the fully adjusted model,Cd was positively associated with femoral neck osteoporosis in men aged≥50 years[odds ratio(OR)=8.563,95%confidence interval(CI)1.888 to 38.845,P<0.05],whereas Se was negatively associated with femoral neck osteoporosis(OR<0.001,95%CI 0 to 0.150,P<0.05).In postmenopausal women,Cd was positively associated with femoral neck osteoporosis risk(OR=2.148,95%CI 1.038 to 4.443,P<0.05),while Se was negatively associated with femoral neck osteoporosis risk(OR=0.027,95%CI 0.001 to 0.986,P<0.05).No significant association was observed between any metal and vertebral osteoporosis(all P>0.05).The WQS model indicated that mixed metal exposure was positively associated with vertebral osteoporosis in men(OR=1.452,95%CI 0.277 to 2.626,P<0.05),whereas no significant association was observed in women.BKMR analysis showed that mixed metal exposure was positively associated with osteoporosis risk at the femoral neck and vertebrae in men,with Cd contributing most to osteoporosis risk,while no association was observed between mixed metal exposure and osteoporosis risk in women.The positive association between mixed blood metal exposure and osteoporosis risk might be partially offset by Se.In stratified analysis,the association between Cd exposure and osteoporosis was stronger in the high dairy consumption group(OR=1.19,95%CI 0.51 to 2.78,P>0.05)than in the low dairy consumption group(OR=3.12,95%CI 1.84 to 5.30,P<0.05),suggesting that frequent dairy consumption may attenuate the positive association between Cd exposure and femoral neck osteoporosis in women.Conclusion:In men aged≥50 years,mixed metal exposure was positively associated with osteoporosis risk at different skeletal sites(femoral neck and vertebra),with Cd contributing most to the risk.In postmenopausal women,no association between mixed metal exposure and osteoporosis risk was observed,indicating clear sex differences.Selenium and dairy consumption may be potential protective factors for osteoporosis in women,whereas such protective effects were not observed in men.展开更多
The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively c...The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.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
OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity ...OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity of plant extract was assessed using DPPH,nitric oxide and H2O2 radical scavenging methods.In vitro anti-inflammatory activity was evaluated using albumin denaturation,membrane stabilization methods at various concentrations.The antibacterial and anti-fungal activity of extracts was also done against micro-organisms:Pseudomonas aurignosa,Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Candida albicans.Quantitative analysis of total phenolics,flavonoids and tannins were also estimated.Female Wistar albino rats(220-260g)were employed and ovaries were surgically removed bilaterally in anaesthesia which causes post-menopausal syndrome in all the groups except sham operated rats.Extracts of Pinus roxburghii stem at 100 and 200mg·kg-1,po.and tamoxifen as standard 1mg·kg-1,po.were given.Acute toxicity study was also done.RESULTS Treatment with Pinus roxburghii extract in two doses significantly(P<0.05)ameliorated surgical ovariectomy induced biochemical and biomechanical changes like decrease in bone density,bone strength,alkaline phosphatase,serum calcium,serum phosphorous and increase in urine hydroxylproline levels.Plant extract also has significant(P<0.05)antioxidant,antimicrobial and anti-inflammatory activities.CONCLUSION The assessments done in present investigation may conclude that the constituents of Pinus roxburghii has significant potential in ameliorating oxidative,inflammatory reactions and possesses anti-microbial;osteobalstic and osteoclastic activities used for calcium homeostatis and improved bone strength in female rats.展开更多
Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quan...Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1—L3 vertebrae were measured based on QCT.Spongy bones of T5—T10 vertebrae were segmented as ROI,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,ML Bagging-OP and Rad Bagging-OP had the best performances for classification of OP.In test set,AUC of ML Bagging-OP,Rad Bagging-OP and DL OP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P>0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of Ax-G±1.96 s),which were highly positively correlated(r=0.910—0.974,all P<0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.展开更多
Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorpti...Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness展开更多
Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did ...Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did not observe any expression of GLP-1 receptors in osteoblasts, indicating that the direct cell target of GLP-1 and its ana- logues might not be osteoblasts but some other types of cells yet to be identified. To elucidate the underlying mecha- nisms, we performed further investigation in the present study and found that GLP-1 receptor was only identified in bone marrow mesenchymal stem cells （BMSCs）. Furthermore, activation of GLP-1 receptor by Ex-4 promoted the differentiation of B MSCs into osteoblast, which was associated with activation of PKA, nuclear translocation of [5- catenin, activation of PI3K/AKT and inhibition of GSK3β. Ex-4 also inhibited the adipocyte differentiation of BM- SCs, as evidenced by inhibition of PPARγ, lipoprotein lipase expression and lipid production. Blockade of GLP-1 receptor, PKA, PI3K or Wnt pathway, or respective knock-down of GLP-1 receptor and β-catenin in BMSCs inhib- ited the Ex-4 mediated effects. The results indicated that the GLP-1 receptor mediated osteoblastic differentiation and bone formation through stimulation of PKA/β-catenin signaling and inhibition of PKA/PI3IC/AKT/GSK3β？ signaling pathway in BMSCs. The findings reveal a new role of GLP-1 receptor for regulating osteoblastic differentia- tion of B MSCs and may provide a molecular basis for novel anabolic therapeutics against osteoporosis.展开更多
基金supported by the Science and Technology Innovation Program of Hunan Province(2025RC3061)the Natural Science Foundation of Hunan Province(2022JJ30828)+2 种基金the Grants from Hunan Provincial Clinical Medicine Research Center for Intelligent Management of Chronic Disease(2023SK4042)the Innovation Foundation For Postgraduate of Hunan Province(CX20240310)the Postgraduate Innovative Project of Central South University(2023XQLH183),China。
文摘Objective:Osteoporosis is a systemic metabolic disease characterized by decreased bone mass,deterioration of bone microstructure,and increased fracture risk.Its occurrence is closely related to sex,age,and lifestyle factors.Environmental exposure to heavy metals and metalloids may also influence its development,although existing findings remain inconsistent.The sex differences in the association between mixed metal exposure and osteoporosis are still unclear.This study aims to investigate whether sex differences exist in the associations between cadmium(Cd),lead(Pb),mercury(Hg),selenium(Se),manganese(Mn),and their mixtures and osteoporosis among men aged≥50 years and postmenopausal women,and to analyze the potential moderating effect of dairy product consumption on these associations.Methods:Data from the National Health and Nutrition Examination Survey(NHANES)2013−2014 and 2017−2018 cycles were used.In men and women separately,generalized linear regression models(univariate regression analysis and multivariate logistic regression)were applied to examine the relationships between single-metal exposure and osteoporosis at the femoral neck and vertebrae.A weighted quantile sum(WQS)model was used to construct a weighted index of mixed metal exposure to quantify the joint effects of multiple metals.Bayesian kernel machine regression(BKMR)was used to systematically evaluate the associations between blood Cd,Pb,Hg,Se,Mn,and their mixtures and osteoporosis at different skeletal sites,capturing potential nonlinear relationships and interactions among metals.Participants were further stratified into high dairy consumption(≥7 times/week)and low dairy consumption(<7 times/week)groups to explore the potential moderating effect of dairy consumption on the association between Cd exposure and osteoporosis.Results:Multivariate logistic regression analysis showed that,in the fully adjusted model,Cd was positively associated with femoral neck osteoporosis in men aged≥50 years[odds ratio(OR)=8.563,95%confidence interval(CI)1.888 to 38.845,P<0.05],whereas Se was negatively associated with femoral neck osteoporosis(OR<0.001,95%CI 0 to 0.150,P<0.05).In postmenopausal women,Cd was positively associated with femoral neck osteoporosis risk(OR=2.148,95%CI 1.038 to 4.443,P<0.05),while Se was negatively associated with femoral neck osteoporosis risk(OR=0.027,95%CI 0.001 to 0.986,P<0.05).No significant association was observed between any metal and vertebral osteoporosis(all P>0.05).The WQS model indicated that mixed metal exposure was positively associated with vertebral osteoporosis in men(OR=1.452,95%CI 0.277 to 2.626,P<0.05),whereas no significant association was observed in women.BKMR analysis showed that mixed metal exposure was positively associated with osteoporosis risk at the femoral neck and vertebrae in men,with Cd contributing most to osteoporosis risk,while no association was observed between mixed metal exposure and osteoporosis risk in women.The positive association between mixed blood metal exposure and osteoporosis risk might be partially offset by Se.In stratified analysis,the association between Cd exposure and osteoporosis was stronger in the high dairy consumption group(OR=1.19,95%CI 0.51 to 2.78,P>0.05)than in the low dairy consumption group(OR=3.12,95%CI 1.84 to 5.30,P<0.05),suggesting that frequent dairy consumption may attenuate the positive association between Cd exposure and femoral neck osteoporosis in women.Conclusion:In men aged≥50 years,mixed metal exposure was positively associated with osteoporosis risk at different skeletal sites(femoral neck and vertebra),with Cd contributing most to the risk.In postmenopausal women,no association between mixed metal exposure and osteoporosis risk was observed,indicating clear sex differences.Selenium and dairy consumption may be potential protective factors for osteoporosis in women,whereas such protective effects were not observed in men.
文摘The treatment and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied,but without a systematic summary currently.This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years,such as Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen and Dipsacus.Based on the existing findings,we concluded the following conclusions:(1)kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads,Wnt/β-catenin,MAPK,PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK,estrogen,CTSK signaling pathway to inhibit osteoclasts of bone resorption.(1)Epimedium,Drynariae Rhizoma,Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.(2)Epimedium,Drynariae Rhizoma,Cnidium,Eucommia,Psoralen,Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway.(2)Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways:Icariin,Naringin,Osthol,Psoralen can regulate BMP-Smads,Wnt/β-catenin signaling pathway to promote bone formation,but also activate OPG/RANKL/RANK,CTSK and other signaling pathway to inhibit bone resorption.(3)The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.
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The project supported by Department of Science and Technology(DST),New Delhi
文摘OBJECTIVE To evaluate antioxidant,anti-inflammatory,antimicrobial activities of Pinus Roxburghii stem bark in vitro and evaluation of in vivo anti-osteoporotic activity in female rats.METHODS The antioxidant activity of plant extract was assessed using DPPH,nitric oxide and H2O2 radical scavenging methods.In vitro anti-inflammatory activity was evaluated using albumin denaturation,membrane stabilization methods at various concentrations.The antibacterial and anti-fungal activity of extracts was also done against micro-organisms:Pseudomonas aurignosa,Escherichia coli,Staphylococcus aureus,Bacillus subtilis and Candida albicans.Quantitative analysis of total phenolics,flavonoids and tannins were also estimated.Female Wistar albino rats(220-260g)were employed and ovaries were surgically removed bilaterally in anaesthesia which causes post-menopausal syndrome in all the groups except sham operated rats.Extracts of Pinus roxburghii stem at 100 and 200mg·kg-1,po.and tamoxifen as standard 1mg·kg-1,po.were given.Acute toxicity study was also done.RESULTS Treatment with Pinus roxburghii extract in two doses significantly(P<0.05)ameliorated surgical ovariectomy induced biochemical and biomechanical changes like decrease in bone density,bone strength,alkaline phosphatase,serum calcium,serum phosphorous and increase in urine hydroxylproline levels.Plant extract also has significant(P<0.05)antioxidant,antimicrobial and anti-inflammatory activities.CONCLUSION The assessments done in present investigation may conclude that the constituents of Pinus roxburghii has significant potential in ameliorating oxidative,inflammatory reactions and possesses anti-microbial;osteobalstic and osteoclastic activities used for calcium homeostatis and improved bone strength in female rats.
文摘Objective To observe the value of artificial intelligence(AI)models based on non-contrast chest CT for measuring bone mineral density(BMD).Methods Totally 380 subjects who underwent both non-contrast chest CT and quantitative CT(QCT)BMD examination were retrospectively enrolled and divided into training set(n=304)and test set(n=76)at a ratio of 8∶2.The mean BMD of L1—L3 vertebrae were measured based on QCT.Spongy bones of T5—T10 vertebrae were segmented as ROI,radiomics(Rad)features were extracted,and machine learning(ML),Rad and deep learning(DL)models were constructed for classification of osteoporosis(OP)and evaluating BMD,respectively.Receiver operating characteristic curves were drawn,and area under the curves(AUC)were calculated to evaluate the efficacy of each model for classification of OP.Bland-Altman analysis and Pearson correlation analysis were performed to explore the consistency and correlation of each model with QCT for measuring BMD.Results Among ML and Rad models,ML Bagging-OP and Rad Bagging-OP had the best performances for classification of OP.In test set,AUC of ML Bagging-OP,Rad Bagging-OP and DL OP for classification of OP was 0.943,0.944 and 0.947,respectively,with no significant difference(all P>0.05).BMD obtained with all the above models had good consistency with those measured with QCT(most of the differences were within the range of Ax-G±1.96 s),which were highly positively correlated(r=0.910—0.974,all P<0.001).Conclusion AI models based on non-contrast chest CT had high efficacy for classification of OP,and good consistency of BMD measurements were found between AI models and QCT.
基金supported by McCabe pilot award and the Penn Center for Musculoskeletal Disorders(NIH/NIAMS P30AR050950)
文摘Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness
文摘Our previous investigation found that exendin-4 （Ex-4） , a peptide analogue of glucagon-like peptide 1 （GLP-1） , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did not observe any expression of GLP-1 receptors in osteoblasts, indicating that the direct cell target of GLP-1 and its ana- logues might not be osteoblasts but some other types of cells yet to be identified. To elucidate the underlying mecha- nisms, we performed further investigation in the present study and found that GLP-1 receptor was only identified in bone marrow mesenchymal stem cells （BMSCs）. Furthermore, activation of GLP-1 receptor by Ex-4 promoted the differentiation of B MSCs into osteoblast, which was associated with activation of PKA, nuclear translocation of [5- catenin, activation of PI3K/AKT and inhibition of GSK3β. Ex-4 also inhibited the adipocyte differentiation of BM- SCs, as evidenced by inhibition of PPARγ, lipoprotein lipase expression and lipid production. Blockade of GLP-1 receptor, PKA, PI3K or Wnt pathway, or respective knock-down of GLP-1 receptor and β-catenin in BMSCs inhib- ited the Ex-4 mediated effects. The results indicated that the GLP-1 receptor mediated osteoblastic differentiation and bone formation through stimulation of PKA/β-catenin signaling and inhibition of PKA/PI3IC/AKT/GSK3β？ signaling pathway in BMSCs. The findings reveal a new role of GLP-1 receptor for regulating osteoblastic differentia- tion of B MSCs and may provide a molecular basis for novel anabolic therapeutics against osteoporosis.
