The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorat...The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.展开更多
Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predic...Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.展开更多
Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, ...Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions.展开更多
Background:Postmenopausal osteoporosis(PMO)is the most common primary osteoporosis in older women.This condition imposes a huge economic and medical burden on society.Aside from western medicine,traditional Chinese me...Background:Postmenopausal osteoporosis(PMO)is the most common primary osteoporosis in older women.This condition imposes a huge economic and medical burden on society.Aside from western medicine,traditional Chinese medicine is also widely used for the treatment of PMO,especially in Asian countries.Zuogui pill(ZGP)and Yougui pill(YGP)are classical formulas for the treatment of PMO with potent clinical effects.This study aimed to explore the potential active compounds,potential targets,and potential mechanisms of ZGP and YGP for the treatment of PMO.Methods:Compounds from ZGP and YGP were collected from three online databases,and these compounds were screened by oral bioavailability and drug-likeness.Their corresponding targets were determined from the Medicine Systems Pharmacology Database and Analysis platform.The corresponding targets for PMO were obtained from two disease databases.The target protein-protein interaction was identified through the STRING platforms and the core targets were ascertained by analyzing the protein-protein interaction network by using Cytoscape software.PMO-related genes were identified via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify specific biological processes,cellular components,molecular functions and key signalling pathways of ZGP and YGP for PMO treatment.Results:A total of 68 compounds were screened from ZGP with 168 putative potential target genes,whereas 99 compounds were screened from YGP with 214 potential target genes associated with PMO.Most of the core components included quercetin and kaempferol,and most of the core targets were TP53,AKT1,MAPK1,JUN,TNF,HSP90AA1,APP,IL6,VEGFA,RELA,MAPK8,NR3C1,EGFR,CXCL8,ESR1,FOS and MAPK14.Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that ZGP and YGP treat PMO primarily via regulation of bone formation and resorption,anti-inflammatory immunity and hormonal regulation.Conclusion:Our data provided insights into the mechanisms,by which ZGP and YGP treat PMO.This study points out a direction for further research into ZGP and YGP monomers and pathways and offers a new clinical treatment option for non-traditional Chinese medicine clinicians in the treatment of PMO.展开更多
Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis(PMO)and related diseases,such as bone degeneration,show multiple adverse effects nowadays.Targeting senescent cells(SnCs)and the ...Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis(PMO)and related diseases,such as bone degeneration,show multiple adverse effects nowadays.Targeting senescent cells(SnCs)and the consequent senescence-associated secretory phenotype(SASP)with a combination of dasatinib and quercetin(DQ)is a recently developed novel therapy for multiple age-related diseases.Herein,we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation,especially senescent mesenchymal stem cells(MSCs)characterized by exhaustion and dysfunction in middle aged rats.Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function.Local administration of DQ and bone morphogenetic protein 2(BMP2)in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration.Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.展开更多
[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ni...[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ninety patients who were treated in Suzhou TCM Hospital from September 2021 to January 2023 were randomly divided into three groups:traditional Chinese medicine group(n=30),western medicine group(n=30)and blank group(n=30).The patients in all the three groups were treated with basic anti-osteoporosis drugs.The patients in the traditional Chinese medicine group were treated with Erxian decoction after PVP,and those in the western medicine group were treated with celecoxib to relieve pain after operation.The visual analogue(VAS)score,Oswestry dysfunction index(ODI)score,TCM syndrome score and serum indexes such as interleukin-6(IL-6)and estrogen E2 were recorded before treatment and 2 weeks,1 month and 3 months after treatment.[Results](i)In terms of pain relief,the VAS score of the western medicine group was lower than that of the traditional Chinese medicine group after 2 weeks of treatment,but there was no significant difference in VAS score between the two groups after 1 month and 3 months,and the pain improvement of the two groups was better than that of the blank group.(ii)After 3 months of treatment,the ODI score in the traditional Chinese medicine group was lower than that in the western medicine group,and the improvement of TCM syndrome in the traditional Chinese medicine group was better than that in the other two groups 1 and 3 months after treatment(P<0.05).(iii)The level of IL-6 in the western medicine group was lower than that in the other groups after 2 weeks,and there was no significant difference between the two groups after 3 months of treatment.After 3 months of treatment,the level of E2 in the traditional Chinese medicine group was higher than that before treatment and higher than that in the western medicine group and the blank group,but there was no significant difference between the two groups(P>0.05).[Conclusions]Both Erxian decoction and non-steroidal anti-inflammatory drugs can relieve residual low back pain after PVP,and their long-term effects are similar,but Erxian decoction has more advantages in alleviating pain,muscle and joint pain and sensory abnormalities in postmenopausal women.Moreover,it is safe and reliable,and is worthy of clinical application.展开更多
Postmenopausal osteoporosis is a kind of degenerative disease,also described as“invisible killer.”Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives.Iro...Postmenopausal osteoporosis is a kind of degenerative disease,also described as“invisible killer.”Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives.Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000μg/L.It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause.In recent years,many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis,and a significant correlation has been found between iron accumulation and fragility fractures.In this review,we summarize and analyze the relevant literature including randomized controlled trials,systematic reviews,and meta-analyses between January 1996 and July 2022.We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation,osteoporosis,and postmenopausal fragility fractures,as well as the main clinical treatment strategies.We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation,in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.展开更多
OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-...OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-Dawley female rats were randomly divided into sham-operated(sham)group and four OVX subgroups.Rats subjected to sham and OVX were treated with the vehicle(OVX,1 mL/100 g weight,n=10),17β-estradiol(E2,50μg·kg-1·d-1),and ZGW at the doses of 2.3(ZGW-L)and 4.6(ZGW-H)g/kg/day lyophilized powder daily for 3 months,respectively.The serum biochemical parameters of 17β-estrogen(17β-E2),tartrate-resistant acid phosphatase(TRACP-5 b)and bone alkaline phosphatase(BALP)were measured by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones.Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur.The gene or protein expression of orexin-A,orexin receptor 1(OX1R),orexin receptor 2(OX2R),osteoprotegerin(OPG)and receptor activator of nuclear factor-κB ligand(RANKL)were assayed by either quantitative polymerase chain reaction or Western blot analysis.RESULTS:Compared with the OVX group,ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and 17β-E2(P<0.01).Meanwhile,ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number,and arranging the trabeculae structure properly.Compared with the OVX group,it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae,and OPG in the tibiae of ZGW groups(P<0.01,<0.05),while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae(P<0.01).CONCLUSION:ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.展开更多
基金supported by the National Natural Science Foundation of China (32072191)Daxing District Major Scientific and Technological Achievements Transformation Project (2020006)+1 种基金Beijing Innovation Team Project of Livestock Industry Technology SystemBeijing Science and Technology Special Project (Z201100002620005)。
文摘The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.
基金supported by Suzhou Special Project for Diagnosis and Treatment Technology of Clinical Key Diseases(No.LCZX202127)。
文摘Background:miRNAs are closely related to bone metabolism.Studies have shown that Erxian decoction can improve bone metabolism,possibly achieving this regulatory effect through miRNA targets.Netinfer was used to predict the miRNA targets of Erxian decoction for the treatment of postmenopausal osteoporosis,and the results were validated by clinical trials.Methods:In this study,we identified possible targets of Erxian decoction in osteoporosis by means of network pharmacological analysis and bioinformatic prediction.Fifteen cases of postmenopausal osteoporosis with kidney Yin and Yang deficiency(In traditional Chinese medicine,kidney Yin nourishes and moistens the tissues of the internal organs of the body,while kidney Yang promotes and warms the tissues of the internal organs of the body.)were treated with Erxian decoction for four weeks,and serum bone metabolism indices(P1NP,osteocalcin,andβ-CTX)and miRNA-335-5p expression were measured before and after treatment.Results:The constructed miRNA postmenopausal osteoporosis related gene network of the effective compound of the Erxian decoction has 296 points and 981 edges.The 39 postmenopausal osteoporosis related genes regulated by miRNA-335-5p were enriched in ossification,while the signaling pathways were enriched in rheumatoid arthritis,the Toll signaling pathway,the HIF-1 signaling pathway,and the MAPK signaling pathway.After taking Erxian decoction,the expression of the serum bone formation index(P1NP,osteocalcin)and miRNA-335-5p gene expression levels increased significantly.The alterations in P1NP and osteocalcin were correlated with the changes in miRNA-335-5p.Conclusion:Circulating miRNA-335-5p may serve as an important target of Erxian decoction in the treatment of postmenopausal women.The effect of Erxian decoction on bone formation is significant,but the underlying mechanism requires further investigation.
文摘Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions.
基金supported by Science and Technology Commission of Shanghai Municipality,China(20Z21900400).
文摘Background:Postmenopausal osteoporosis(PMO)is the most common primary osteoporosis in older women.This condition imposes a huge economic and medical burden on society.Aside from western medicine,traditional Chinese medicine is also widely used for the treatment of PMO,especially in Asian countries.Zuogui pill(ZGP)and Yougui pill(YGP)are classical formulas for the treatment of PMO with potent clinical effects.This study aimed to explore the potential active compounds,potential targets,and potential mechanisms of ZGP and YGP for the treatment of PMO.Methods:Compounds from ZGP and YGP were collected from three online databases,and these compounds were screened by oral bioavailability and drug-likeness.Their corresponding targets were determined from the Medicine Systems Pharmacology Database and Analysis platform.The corresponding targets for PMO were obtained from two disease databases.The target protein-protein interaction was identified through the STRING platforms and the core targets were ascertained by analyzing the protein-protein interaction network by using Cytoscape software.PMO-related genes were identified via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify specific biological processes,cellular components,molecular functions and key signalling pathways of ZGP and YGP for PMO treatment.Results:A total of 68 compounds were screened from ZGP with 168 putative potential target genes,whereas 99 compounds were screened from YGP with 214 potential target genes associated with PMO.Most of the core components included quercetin and kaempferol,and most of the core targets were TP53,AKT1,MAPK1,JUN,TNF,HSP90AA1,APP,IL6,VEGFA,RELA,MAPK8,NR3C1,EGFR,CXCL8,ESR1,FOS and MAPK14.Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that ZGP and YGP treat PMO primarily via regulation of bone formation and resorption,anti-inflammatory immunity and hormonal regulation.Conclusion:Our data provided insights into the mechanisms,by which ZGP and YGP treat PMO.This study points out a direction for further research into ZGP and YGP monomers and pathways and offers a new clinical treatment option for non-traditional Chinese medicine clinicians in the treatment of PMO.
基金Frontiers Science Center for Materiobiology and Dynamic Chemistry(No.JKVD1211002)Natural Science Foundation of China for Innovative Research Groups(No.51621002)+1 种基金National Natural Science Foundation of China(Nos.81571828,31971264,32101151)Basic Science Center Project of National Natural Science Foundation of China(T2288102)。
文摘Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis(PMO)and related diseases,such as bone degeneration,show multiple adverse effects nowadays.Targeting senescent cells(SnCs)and the consequent senescence-associated secretory phenotype(SASP)with a combination of dasatinib and quercetin(DQ)is a recently developed novel therapy for multiple age-related diseases.Herein,we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation,especially senescent mesenchymal stem cells(MSCs)characterized by exhaustion and dysfunction in middle aged rats.Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function.Local administration of DQ and bone morphogenetic protein 2(BMP2)in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration.Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.
基金Supported by National Natural Science Foundation of China(82074456)Suzhou Health Commission,Gusu Health Talent Project(GSWS2020090).
文摘[Objectives]To explore the clinical effect of Erxian decoction on relieving low back pain after percutaneous vertebroplasty(PVP)of vertebral compression fracture caused by postmenopausal osteoporosis(PMOP).[Methods]Ninety patients who were treated in Suzhou TCM Hospital from September 2021 to January 2023 were randomly divided into three groups:traditional Chinese medicine group(n=30),western medicine group(n=30)and blank group(n=30).The patients in all the three groups were treated with basic anti-osteoporosis drugs.The patients in the traditional Chinese medicine group were treated with Erxian decoction after PVP,and those in the western medicine group were treated with celecoxib to relieve pain after operation.The visual analogue(VAS)score,Oswestry dysfunction index(ODI)score,TCM syndrome score and serum indexes such as interleukin-6(IL-6)and estrogen E2 were recorded before treatment and 2 weeks,1 month and 3 months after treatment.[Results](i)In terms of pain relief,the VAS score of the western medicine group was lower than that of the traditional Chinese medicine group after 2 weeks of treatment,but there was no significant difference in VAS score between the two groups after 1 month and 3 months,and the pain improvement of the two groups was better than that of the blank group.(ii)After 3 months of treatment,the ODI score in the traditional Chinese medicine group was lower than that in the western medicine group,and the improvement of TCM syndrome in the traditional Chinese medicine group was better than that in the other two groups 1 and 3 months after treatment(P<0.05).(iii)The level of IL-6 in the western medicine group was lower than that in the other groups after 2 weeks,and there was no significant difference between the two groups after 3 months of treatment.After 3 months of treatment,the level of E2 in the traditional Chinese medicine group was higher than that before treatment and higher than that in the western medicine group and the blank group,but there was no significant difference between the two groups(P>0.05).[Conclusions]Both Erxian decoction and non-steroidal anti-inflammatory drugs can relieve residual low back pain after PVP,and their long-term effects are similar,but Erxian decoction has more advantages in alleviating pain,muscle and joint pain and sensory abnormalities in postmenopausal women.Moreover,it is safe and reliable,and is worthy of clinical application.
基金Outstanding Youth Science Fund Project of the First Affiliated Hospital of Bengbu Medical College(No.2021byyfyyq04),China.
文摘Postmenopausal osteoporosis is a kind of degenerative disease,also described as“invisible killer.”Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives.Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000μg/L.It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause.In recent years,many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis,and a significant correlation has been found between iron accumulation and fragility fractures.In this review,we summarize and analyze the relevant literature including randomized controlled trials,systematic reviews,and meta-analyses between January 1996 and July 2022.We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation,osteoporosis,and postmenopausal fragility fractures,as well as the main clinical treatment strategies.We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation,in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.
基金Supported by Traditional Chinese and Western Medicine Clinical Medicine Brand Construction Project of Jiangsu Higher Education Institutions(PhaseⅡ)National Natural Science Foundation of China(No.81573874 and81873229)。
文摘OBJECTIVE:To investigate the protective effects of Zuogui Wan(左归丸,ZGW)on bone loss induced by ovariectomy(OVX)and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model.METHODS:Fifty Sprague-Dawley female rats were randomly divided into sham-operated(sham)group and four OVX subgroups.Rats subjected to sham and OVX were treated with the vehicle(OVX,1 mL/100 g weight,n=10),17β-estradiol(E2,50μg·kg-1·d-1),and ZGW at the doses of 2.3(ZGW-L)and 4.6(ZGW-H)g/kg/day lyophilized powder daily for 3 months,respectively.The serum biochemical parameters of 17β-estrogen(17β-E2),tartrate-resistant acid phosphatase(TRACP-5 b)and bone alkaline phosphatase(BALP)were measured by enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones.Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur.The gene or protein expression of orexin-A,orexin receptor 1(OX1R),orexin receptor 2(OX2R),osteoprotegerin(OPG)and receptor activator of nuclear factor-κB ligand(RANKL)were assayed by either quantitative polymerase chain reaction or Western blot analysis.RESULTS:Compared with the OVX group,ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and 17β-E2(P<0.01).Meanwhile,ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number,and arranging the trabeculae structure properly.Compared with the OVX group,it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae,and OPG in the tibiae of ZGW groups(P<0.01,<0.05),while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae(P<0.01).CONCLUSION:ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.
