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
Objective: To observe the efficacy and safety of Yigu capsule (益骨胶囊, YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism. Methods: The c...Objective: To observe the efficacy and safety of Yigu capsule (益骨胶囊, YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism. Methods: The clinical study was conducted in a prospective, randomized, double blinded method lasting for 6 months with placebo and positive control. Two hundred and ten PMO patients with confirmed diagnosis were assigned into the YGC group, the calciferol group and the placebo group. Besides being administered element calcium, they were treated with YGC, calciferol capsule and placebo capsule respectively. And such symptoms as newly found fracture and ostealgia, bone mineral density (BMD) of the 2nd-4th lumbar vertebrae (L_ 2-4 ) and upper femur, blood and urinary indexes for bone metabolism, sex hormone level and adverse reaction that occurred in patients were observed.Results: In the YGC group, the total effective rate was 95.50%, with no new occurrence of fractures, which was significantly better than that in the other two groups (P<0.05). Moreover, in the YGC group,the increase rate of BMD was 9.83% in L_ 2-4 , 4.09% in femoral neck, 4.60% in Wards triangle, 3.00% in greater trochanter, which was also better than that in the placebo group (P<0.05, P<0.01). As compared with the placebo group, levels in the YGC group of urinary oxyproline hydroxyproline/creatinine, urinary calcium/creatinine were significantly lower, serum and bone alkaline phosphatase, osteocalcin, estradiol and estradiol/testosterone were significantly higher, but no difference was shown in the comparison of testosterone level. In the observation period, no abnormality in blood or urine routine, liver or renal function was found. Only mild, transient gastro-intestinal response occurred in individual patients, but it did not affect the treatment. Conclusion: YGC could treat PMO effectively, as it could obviously increase the BMD of lumbar vertebrae and coxafemoral bone, elevate the alleviating rate of ostealgia and incessant motion time, yet causing no newly found compressive fracture of vertebrae, or and any related adverse reaction. YGC could not only promote the formation, but also inhibit the absorption of bone as well as increase the sex hormone level. Therefore, it is a pure Chinese herbal compound preparation worthy of further research and development.展开更多
Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in ...Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group(P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin(r=–0.161, P=0.003) and OPG(r=–0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin(β=–0.165, P=0.009) and BMD(β=–0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX(β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.展开更多
Objectives: To study the partial mechanism of treating postmenopausal osteoporosis patients (POPs) using the ancient recipe of Qing’E Formula (QEF) by observing its effects on bone metabolic markers and VDR mRNA expr...Objectives: To study the partial mechanism of treating postmenopausal osteoporosis patients (POPs) using the ancient recipe of Qing’E Formula (QEF) by observing its effects on bone metabolic markers and VDR mRNA expression in primary POPs. Methods: Analysis was performed on 120 outpatient and inpatient POPs treated in our hospital between January and October 2013, where the patients were randomly divided into Qing’E group (QEF + Caltrate), Calcitriol group (Caltrate + Calcitriol soft capsules), and Compare group (Caltrate), each with a follow-up period of 1 year. Statistical analysis was then performed on bone mineral density, blood bone metabolic markers (β-CTX, N-MID, T-PINP) and changes in VDR mRNA expressions in the POPs before and after the treatments. Results: Prior to the treatments, bone mineral density and blood β-CTX, N-MID, T-PINP and VDR mRNA expression in the 3 groups of POPs exhibited no statistically significant differences, and the blood β-CTX, N-MID, T-PINP and VDR mRNA expression in the control group showed no statistically significant differences before and after the treatments. There were no significant differences in bone mineral density in the Qing’E group and the Calcitriol group before and after the treatments whereas the bone mineral density decreased in the control group after the treatments. As for blood β-CTX, N-MID, T-PINP and VDR mRNA expression, the measurements in POPs in the Qing’E group and the Calcitriol group were significantly higher than that of the control group. Conclusion: By adjusting the VDR mRNA expression, the QEF, a kidney-invigorating Chinese herbal formula, is capable of activating bone metabolism to prohibit further losses of bone mass, thereby preventing the deterioration of osteoporosis.展开更多
Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
Objective: To explore the clinical efficacy of Zoledronic Acid Injection in the treatment of postmenopausal osteoporosis with different bone turnover rates. Methods: A total of 63 patients diagnosed with postmenopausa...Objective: To explore the clinical efficacy of Zoledronic Acid Injection in the treatment of postmenopausal osteoporosis with different bone turnover rates. Methods: A total of 63 patients diagnosed with postmenopausal osteoporosis were included in this study. Each patient was administrated 5 mg/100mL Zoledronic Acid (Aclasta) intravenously once and then given a one-year prescription of 600 mg/d oral Caltrate. The bone turnover parameters (PINP, β-cross, N-MID) were measured prior to the injection of Zoledronic Acid while the bone mineral density (BMD) and the pain scores of each patient were tested before treatment and after the one-year medication. On this basis, the patients were divided into several groups according to their bone turnover rates for intergroup comparison of treatment outcomes. Results: BMD results and pain scores of all participants were significantly improved at different levels after treatment. However, these improvements had no significant differences between the patients with high and low bone turnover rates. Conclusion: Zoledronic Acid Injection can relieve bone pain, enhance the quality of life and increase the BMD in patients with postmenopausal osteoporosis, regardless of the bone turnover status.展开更多
To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteoporosis. Th...To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteoporosis. The changes were compared in bone mineral density (BMD), bone metabolism markers and adverse events after 12 months oral administration of risedronate sodium. BMD was measured by dual energy X-ray absorptionmetry (DEXA) and bone turnover marker was detected. The results showed that there was a significant increase in BMD of the lumbar spine ( 3.29 %±1.18 %, 4.51 %±1.64 % respectively) after 6 and 12 months in the risedronate treatment group versus placebo control group (-0.62 %±0.24 %, 0.48 %±0.18 % respectively). Bone turnover was decreased to a stable nadir over 6 and 12 months for resorption markers [N-Telopeptide (NTx), P<0.05] and over 12 months for formation marker (ALP, P<0.05; BGP, P<0.05). The safety profile of risedronate sodium was similar to that of placebo. There were no trends toward increased frequency of any adverse experience except for gastrointestinal symptoms (7.1 %), rash (7.1 %) and hematuria (3.6 %), which were usually mild, transient, and resolved with continued treatment. It was concluded that risedronate was an efficacious and safe drug in treatment of postmenopausal osteoporosis.展开更多
A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once...A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.展开更多
Objective: To observe the effect of acupuncture on serum interlukin-6 (IL-6) level in women with postmenopausal osteoporosis. Methods: 59 cases of postmenopausal osteoporosis women were randomly divided into acupunctu...Objective: To observe the effect of acupuncture on serum interlukin-6 (IL-6) level in women with postmenopausal osteoporosis. Methods: 59 cases of postmenopausal osteoporosis women were randomly divided into acupunctue group(n= 32) and calcium D group(n= 27). In acupuncture group, Zusanli (ST 36), Sanyinjiao (SP 6),Shenshu (BL 23) and Pishu (BL 20) were punctured, 3 times every week, continuously for 6 months. In control group,patients were ordered to take Calcium D, one pill (containing 1500 mg calcium carbonate and VitD3) every morning,continuously for 6 months. Serum IL-6 was detected using radioimmunoassay. Results:After six months' treatment, the result showed that in acupuncture group serum IL-6 calcium level lowered while in control group serum IL-6 content increased. Statistical analysis indicates that there are no significant differences between two groups or between pretreatment and post-treatment in every single group(P ＞0.05). Conclusion: Although no statistical difference was found between two groups, acupuncture could decrease secretion of IL-6 in postmenopausal osteoporosis women to a certain degree, refrain the activity of osteoclast and improve the quality of bone.展开更多
Objective:To study the correlation of serum total bilirubin (TBIL) content with bone metabolism and micro-inflammatory response in patients with postmenopausal osteoporosis. Methods: The patients diagnosed with postme...Objective:To study the correlation of serum total bilirubin (TBIL) content with bone metabolism and micro-inflammatory response in patients with postmenopausal osteoporosis. Methods: The patients diagnosed with postmenopausal osteoporosis by DEXA in Wuhan Zhongyuan Hospital between February 2015 and December 2017 were chosen as the OP group, the postmenopausal women who were proven to have normal bone mineral density by DEXA during the same period were chosen as control group, and the TBIL, bone metabolism markers, bone metabolism biochemical indexes and inflammation indexes were determined. Results: Serum TBIL, PINP, OPG, SOD, T-AOC and IL-10 levels as well as peripheral blood FOXP3 expression of OP group were significantly lower than those of control group whereas serum NTX, CTX, RANKL, AOPP, IL-17 and TNF-α levels as well as peripheral blood NOX1, FoxO3a, ROR-γt and NF-κB expression were significantly higher than those of control group;serum TBIL content of OP group was positively correlated with serum PINP, OPG, SOD, T-AOC and IL-10 levels as well as peripheral blood FOXP3 expression, and negatively correlated with serum NTX, CTX, RANKL, AOPP, IL-17 and TNF-α levels as well as peripheral blood NOX1, FoxO3a, ROR-γt and NF-κB expression.Conclusion: The decrease of serum TBIL in patients with postmenopausal osteoporosis can damage the bone metabolism and aggravate the micro-inflammatory response.展开更多
Objectives: Although bisphosphonates (BPs) are effective for the majority of patients with osteoporosis, some individuals do not adequately respond to these drugs. The objective of this study was to estimate the preva...Objectives: Although bisphosphonates (BPs) are effective for the majority of patients with osteoporosis, some individuals do not adequately respond to these drugs. The objective of this study was to estimate the prevalence of true BP non-responders who showed insufficient response after both oral BPs and intravenous ibandronate. Methods: Among 146 consecutive patients with postmenopausal osteoporosis who received oral BP monotherapy for more than 12 months, insufficient responders to oral BP monotherapy were switched to intravenous ibandronate injection and followed for more than 12 months. Serum N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) concentrations were measured. Patients who also showed insufficient response to intravenous ibandronate were defined as true BP non-responders. Insufficient response to BP therapy was evaluated based on the serum NTX reduction cut-off for minimum significant change. Results: Sixty-one patients (41.8%) were diagnosed as oral BP non-responders. Fourteen patients who switched to intravenous ibandronate and had complete data available were used for final analysis. After switching to intravenous ibandronate, both NTX and BAP decreased significantly (p Conclusion: These results estimated that as few as 9% - 15% (i.e., 21.4% - 35.7% of 41.8%) or as many as 24% - 27% (i.e., 57.1% - 64.3% of 41.8%) of patents might be true BP non-responders.展开更多
To establish and evaluate the.osteoporosis model in ovariectomized mice,so as to provide appropriate model for different drug interventions in later period.In this study,ten female C57BL/6 mice aged 10~12 weeks were s...To establish and evaluate the.osteoporosis model in ovariectomized mice,so as to provide appropriate model for different drug interventions in later period.In this study,ten female C57BL/6 mice aged 10~12 weeks were selected and randomly divided into sham operation control(sham)group and ovariectomized osteoporosis model(OVX)group.At eight weeks after operation,the mice were sacrificed after blood collection.Their femur on one side was separated,soft tissue was removed,and then frozen section was made.The other side was examined by Micro CT.Lastly,their levels of serum calcium,phosphorus and magnesium were measured and observed by histopathology and immunofluorescence.展开更多
Objective:To investigate the effects of Bushen Jiangu decoction (kidney invigorating and bone invigorating decoction) on sex hormones and cytokines in women with postmenopausal osteoporosis (PMOP).Methods:From Februar...Objective:To investigate the effects of Bushen Jiangu decoction (kidney invigorating and bone invigorating decoction) on sex hormones and cytokines in women with postmenopausal osteoporosis (PMOP).Methods:From February 2014 to May 2016, 98 PMOP patients were selected as the research objects, randomly divided into observation group and control group (n=49). Two groups were given oral alendronate 70 mg/ times, 1 time/week, Caltrate D 1 tablets, 2 times/d. The observation group was given Bushen Jiangu decoction, daily 1 agent. The treatment period was 6 months. The fasting peripheral venous blood was collected before and after treatment and analyzed by automated chemiluminescence immunoassay analyzer for determination of serum estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH), prolactin (PRL), testosterone (T) and type I collagen carboxy terminal peptide (CTX), type I precollagen (PINP);using radioimmunoassay method of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), insulin-like growth factor (IGF-1).Results:The E2 and T levels of the observation group after treatment were significantly increased compared with before treatment (P<0.05). The IL-6 and TNF-alpha of the observation group after treatment were lower than before treatment, while IGF-1 increased than that before treatment, significantly better than the control group (P<0.05);The CTX, P of NP of the observation group after treatment was significantly lower than the control group during the same period (P<0.05).Conclusions:The combination of Bushen Jiangu decoction combined with sodium hyaluronate can effectively improve the level of sex hormones in patients with PMOP, regulate the level of IL-6, TNF-alpha and IGF-1, inhibit the formation of osteoclasts and bone resorption, and improve the treatment effect of osteoporosis.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
Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass,destruction of bone microstructure,increased brittleness and therefore fracture.At present,the main treatment of Western...Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass,destruction of bone microstructure,increased brittleness and therefore fracture.At present,the main treatment of Western medicine is drug therapy such as bisphosphonates,calcitriol,vitamin D,etc.However,long-term use of these drugs may bring some adverse reactions.Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions.Therefore,Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years.Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism.Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis.展开更多
Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel...Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.展开更多
Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
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the Natural Science Foundation of Guangdong Province (No. 990475), the Post-doctoral Programs Funds of China(No.1999-26), the Funds of TCM in Guangdong Province (No. 99580)
文摘Objective: To observe the efficacy and safety of Yigu capsule (益骨胶囊, YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism. Methods: The clinical study was conducted in a prospective, randomized, double blinded method lasting for 6 months with placebo and positive control. Two hundred and ten PMO patients with confirmed diagnosis were assigned into the YGC group, the calciferol group and the placebo group. Besides being administered element calcium, they were treated with YGC, calciferol capsule and placebo capsule respectively. And such symptoms as newly found fracture and ostealgia, bone mineral density (BMD) of the 2nd-4th lumbar vertebrae (L_ 2-4 ) and upper femur, blood and urinary indexes for bone metabolism, sex hormone level and adverse reaction that occurred in patients were observed.Results: In the YGC group, the total effective rate was 95.50%, with no new occurrence of fractures, which was significantly better than that in the other two groups (P<0.05). Moreover, in the YGC group,the increase rate of BMD was 9.83% in L_ 2-4 , 4.09% in femoral neck, 4.60% in Wards triangle, 3.00% in greater trochanter, which was also better than that in the placebo group (P<0.05, P<0.01). As compared with the placebo group, levels in the YGC group of urinary oxyproline hydroxyproline/creatinine, urinary calcium/creatinine were significantly lower, serum and bone alkaline phosphatase, osteocalcin, estradiol and estradiol/testosterone were significantly higher, but no difference was shown in the comparison of testosterone level. In the observation period, no abnormality in blood or urine routine, liver or renal function was found. Only mild, transient gastro-intestinal response occurred in individual patients, but it did not affect the treatment. Conclusion: YGC could treat PMO effectively, as it could obviously increase the BMD of lumbar vertebrae and coxafemoral bone, elevate the alleviating rate of ostealgia and incessant motion time, yet causing no newly found compressive fracture of vertebrae, or and any related adverse reaction. YGC could not only promote the formation, but also inhibit the absorption of bone as well as increase the sex hormone level. Therefore, it is a pure Chinese herbal compound preparation worthy of further research and development.
基金supported by grants from National Natural Science Foundation of China(No.81473492 and No.81273907)Health Department of Hubei Province,China(No.2012Z-Z01)
文摘Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group(P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin(r=–0.161, P=0.003) and OPG(r=–0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin(β=–0.165, P=0.009) and BMD(β=–0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX(β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.
文摘Objectives: To study the partial mechanism of treating postmenopausal osteoporosis patients (POPs) using the ancient recipe of Qing’E Formula (QEF) by observing its effects on bone metabolic markers and VDR mRNA expression in primary POPs. Methods: Analysis was performed on 120 outpatient and inpatient POPs treated in our hospital between January and October 2013, where the patients were randomly divided into Qing’E group (QEF + Caltrate), Calcitriol group (Caltrate + Calcitriol soft capsules), and Compare group (Caltrate), each with a follow-up period of 1 year. Statistical analysis was then performed on bone mineral density, blood bone metabolic markers (β-CTX, N-MID, T-PINP) and changes in VDR mRNA expressions in the POPs before and after the treatments. Results: Prior to the treatments, bone mineral density and blood β-CTX, N-MID, T-PINP and VDR mRNA expression in the 3 groups of POPs exhibited no statistically significant differences, and the blood β-CTX, N-MID, T-PINP and VDR mRNA expression in the control group showed no statistically significant differences before and after the treatments. There were no significant differences in bone mineral density in the Qing’E group and the Calcitriol group before and after the treatments whereas the bone mineral density decreased in the control group after the treatments. As for blood β-CTX, N-MID, T-PINP and VDR mRNA expression, the measurements in POPs in the Qing’E group and the Calcitriol group were significantly higher than that of the control group. Conclusion: By adjusting the VDR mRNA expression, the QEF, a kidney-invigorating Chinese herbal formula, is capable of activating bone metabolism to prohibit further losses of bone mass, thereby preventing the deterioration of osteoporosis.
文摘Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
文摘Objective: To explore the clinical efficacy of Zoledronic Acid Injection in the treatment of postmenopausal osteoporosis with different bone turnover rates. Methods: A total of 63 patients diagnosed with postmenopausal osteoporosis were included in this study. Each patient was administrated 5 mg/100mL Zoledronic Acid (Aclasta) intravenously once and then given a one-year prescription of 600 mg/d oral Caltrate. The bone turnover parameters (PINP, β-cross, N-MID) were measured prior to the injection of Zoledronic Acid while the bone mineral density (BMD) and the pain scores of each patient were tested before treatment and after the one-year medication. On this basis, the patients were divided into several groups according to their bone turnover rates for intergroup comparison of treatment outcomes. Results: BMD results and pain scores of all participants were significantly improved at different levels after treatment. However, these improvements had no significant differences between the patients with high and low bone turnover rates. Conclusion: Zoledronic Acid Injection can relieve bone pain, enhance the quality of life and increase the BMD in patients with postmenopausal osteoporosis, regardless of the bone turnover status.
文摘To evaluate the efficacy and safety of risedronate sodium in treatment of postmenopausal osteoporosis, one-year randomized, double blind clinical trial was performed among 54 women with postmenopausal osteoporosis. The changes were compared in bone mineral density (BMD), bone metabolism markers and adverse events after 12 months oral administration of risedronate sodium. BMD was measured by dual energy X-ray absorptionmetry (DEXA) and bone turnover marker was detected. The results showed that there was a significant increase in BMD of the lumbar spine ( 3.29 %±1.18 %, 4.51 %±1.64 % respectively) after 6 and 12 months in the risedronate treatment group versus placebo control group (-0.62 %±0.24 %, 0.48 %±0.18 % respectively). Bone turnover was decreased to a stable nadir over 6 and 12 months for resorption markers [N-Telopeptide (NTx), P<0.05] and over 12 months for formation marker (ALP, P<0.05; BGP, P<0.05). The safety profile of risedronate sodium was similar to that of placebo. There were no trends toward increased frequency of any adverse experience except for gastrointestinal symptoms (7.1 %), rash (7.1 %) and hematuria (3.6 %), which were usually mild, transient, and resolved with continued treatment. It was concluded that risedronate was an efficacious and safe drug in treatment of postmenopausal osteoporosis.
文摘A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.
文摘Objective: To observe the effect of acupuncture on serum interlukin-6 (IL-6) level in women with postmenopausal osteoporosis. Methods: 59 cases of postmenopausal osteoporosis women were randomly divided into acupunctue group(n= 32) and calcium D group(n= 27). In acupuncture group, Zusanli (ST 36), Sanyinjiao (SP 6),Shenshu (BL 23) and Pishu (BL 20) were punctured, 3 times every week, continuously for 6 months. In control group,patients were ordered to take Calcium D, one pill (containing 1500 mg calcium carbonate and VitD3) every morning,continuously for 6 months. Serum IL-6 was detected using radioimmunoassay. Results:After six months' treatment, the result showed that in acupuncture group serum IL-6 calcium level lowered while in control group serum IL-6 content increased. Statistical analysis indicates that there are no significant differences between two groups or between pretreatment and post-treatment in every single group(P ＞0.05). Conclusion: Although no statistical difference was found between two groups, acupuncture could decrease secretion of IL-6 in postmenopausal osteoporosis women to a certain degree, refrain the activity of osteoclast and improve the quality of bone.
文摘Objective:To study the correlation of serum total bilirubin (TBIL) content with bone metabolism and micro-inflammatory response in patients with postmenopausal osteoporosis. Methods: The patients diagnosed with postmenopausal osteoporosis by DEXA in Wuhan Zhongyuan Hospital between February 2015 and December 2017 were chosen as the OP group, the postmenopausal women who were proven to have normal bone mineral density by DEXA during the same period were chosen as control group, and the TBIL, bone metabolism markers, bone metabolism biochemical indexes and inflammation indexes were determined. Results: Serum TBIL, PINP, OPG, SOD, T-AOC and IL-10 levels as well as peripheral blood FOXP3 expression of OP group were significantly lower than those of control group whereas serum NTX, CTX, RANKL, AOPP, IL-17 and TNF-α levels as well as peripheral blood NOX1, FoxO3a, ROR-γt and NF-κB expression were significantly higher than those of control group;serum TBIL content of OP group was positively correlated with serum PINP, OPG, SOD, T-AOC and IL-10 levels as well as peripheral blood FOXP3 expression, and negatively correlated with serum NTX, CTX, RANKL, AOPP, IL-17 and TNF-α levels as well as peripheral blood NOX1, FoxO3a, ROR-γt and NF-κB expression.Conclusion: The decrease of serum TBIL in patients with postmenopausal osteoporosis can damage the bone metabolism and aggravate the micro-inflammatory response.
文摘Objectives: Although bisphosphonates (BPs) are effective for the majority of patients with osteoporosis, some individuals do not adequately respond to these drugs. The objective of this study was to estimate the prevalence of true BP non-responders who showed insufficient response after both oral BPs and intravenous ibandronate. Methods: Among 146 consecutive patients with postmenopausal osteoporosis who received oral BP monotherapy for more than 12 months, insufficient responders to oral BP monotherapy were switched to intravenous ibandronate injection and followed for more than 12 months. Serum N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) concentrations were measured. Patients who also showed insufficient response to intravenous ibandronate were defined as true BP non-responders. Insufficient response to BP therapy was evaluated based on the serum NTX reduction cut-off for minimum significant change. Results: Sixty-one patients (41.8%) were diagnosed as oral BP non-responders. Fourteen patients who switched to intravenous ibandronate and had complete data available were used for final analysis. After switching to intravenous ibandronate, both NTX and BAP decreased significantly (p Conclusion: These results estimated that as few as 9% - 15% (i.e., 21.4% - 35.7% of 41.8%) or as many as 24% - 27% (i.e., 57.1% - 64.3% of 41.8%) of patents might be true BP non-responders.
文摘To establish and evaluate the.osteoporosis model in ovariectomized mice,so as to provide appropriate model for different drug interventions in later period.In this study,ten female C57BL/6 mice aged 10~12 weeks were selected and randomly divided into sham operation control(sham)group and ovariectomized osteoporosis model(OVX)group.At eight weeks after operation,the mice were sacrificed after blood collection.Their femur on one side was separated,soft tissue was removed,and then frozen section was made.The other side was examined by Micro CT.Lastly,their levels of serum calcium,phosphorus and magnesium were measured and observed by histopathology and immunofluorescence.
文摘Objective:To investigate the effects of Bushen Jiangu decoction (kidney invigorating and bone invigorating decoction) on sex hormones and cytokines in women with postmenopausal osteoporosis (PMOP).Methods:From February 2014 to May 2016, 98 PMOP patients were selected as the research objects, randomly divided into observation group and control group (n=49). Two groups were given oral alendronate 70 mg/ times, 1 time/week, Caltrate D 1 tablets, 2 times/d. The observation group was given Bushen Jiangu decoction, daily 1 agent. The treatment period was 6 months. The fasting peripheral venous blood was collected before and after treatment and analyzed by automated chemiluminescence immunoassay analyzer for determination of serum estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH), prolactin (PRL), testosterone (T) and type I collagen carboxy terminal peptide (CTX), type I precollagen (PINP);using radioimmunoassay method of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), insulin-like growth factor (IGF-1).Results:The E2 and T levels of the observation group after treatment were significantly increased compared with before treatment (P<0.05). The IL-6 and TNF-alpha of the observation group after treatment were lower than before treatment, while IGF-1 increased than that before treatment, significantly better than the control group (P<0.05);The CTX, P of NP of the observation group after treatment was significantly lower than the control group during the same period (P<0.05).Conclusions:The combination of Bushen Jiangu decoction combined with sodium hyaluronate can effectively improve the level of sex hormones in patients with PMOP, regulate the level of IL-6, TNF-alpha and IGF-1, inhibit the formation of osteoclasts and bone resorption, and improve the treatment effect of osteoporosis.
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 Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2019037)National Natural Science Foundation of China(No.82001481)。
文摘Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass,destruction of bone microstructure,increased brittleness and therefore fracture.At present,the main treatment of Western medicine is drug therapy such as bisphosphonates,calcitriol,vitamin D,etc.However,long-term use of these drugs may bring some adverse reactions.Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions.Therefore,Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years.Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism.Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis.
基金supported by the National Natural Science Foundation of China (81921002,81900970,82130027)Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
