Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

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.

Postmenopausal Osteoporosis and Osteopenia Management with a Combination of Once-Monthly Oral Ibandronate and Cholecalciferol—A Systematic Review

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.

Erxian decoction potentially prevents postmenopausal osteoporosis by modulating miR-335: a study based on bioinformatics analysis and preliminary clinical case validation

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.

Study on the Correlation between Adiponectin and Bone Mineral Density in Postmenopausal Women from Guangxi Zhuang Autonomous Region

Objectives: To explore the relationship between adiponectin (APN) and bone mineral density in this Zhuang ethnic group, thus providing a basis underpinning the prevention and treatment of osteoporosis (OP). Methods: Zhuang women over 50 years old in Guangxi Zhuang Autonomous Region were included in the study. The broadband ultrasound attenuation (BUA) was adopted as the reference to calculate the T value. Quantitative ultrasonic bone density was measured on the right. Body composition measuring instrument was used to measure weight, fat, and muscle mass. Plasma APN level was detected by ELISA and blood lipids were detected by enzymatic method. Results: Plasma APN level was found with significant differences in the normal bone mineral density group, bone mineral density reduction group, and osteoporosis group (P β = −0.176, P = 0.001) when the partial correlation coefficient of APN is −0.210. Elevated APN was an independent risk factor for bone mineral density reduction (OR = 1.191, 95%CI: 1.004 - 1.407, P = 0.04) and OP (OR = 1.1337, 95%CI: 1.137 - 1.572, P Conclusion: Increased APN in postmenopausal women of Zhuang is an independent risk factor for OP. The application of APN in the OP screening and prevention of middle-aged and ageing Zhuang women still needs further research.

A Clinical Study of Yigu Capsule (益骨胶囊) in Treating Postmenopausal Osteoporosis

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.

Efficacy and Safety of Risedronate Sodium in Treatment of Postmenopausal Osteoporosis

Summary： 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 %±41.18 %, 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.

Association of Serum Dkk-1 Levels with β-catenin in Patients with Postmenopausal Osteoporosis

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.

Bisphosphonates Zoledronate and Alendronate for the Management of Postmenopausal Osteoporosis

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.

Curative Effect Analysis of Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis with Different Bone Turnover Rates

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.

A candidate identification questionnaire for postmenopausal osteoporosis patients switched from daily or weekly bisphosphonate to once-monthly ibandronate: An open, prospective, multicenter study—BONCURE study

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.

Insulin-Like Growth Factor-1 and Osteocalcin Are Correlated with Markers of Osteoporosis in Postmenopausal Women with Type-2 Diabetes

Objective: The study was conducted to evaluate the relation between insulin-like growth factor-1 and osteocalcin and markers of bone modulation (osteoprotegerin;OPG, receptor activator nuclear kappa B;RANK and RANK ligand;RANKL) in postmenopausal Type 2 diabetic women with and without osteoporosis. Methods: The study was conducted on 90 female divided into three groups (30 each). Group I included healthy postmenopausal women as a control, Group II included diabetic postmenopausal women without osteoporosis Group III included diabetic postmenopausal women with osteoporosis. Fasting blood samples were obtained for the determination of blood glucose, HbA1c, total and ionized calcium, OPG, RANK and RANKL. Also the levels of IGF-1 and osteocalcin were assessed. Results: In postmenopausal Type 2 diabetic women, the osteoporosis resulted in derangement in OPG/sRANKL system. The serum level of OPG was elevated while sRANKL declines in osteoporotic postmenopausal Type 2 diabetic women. IGF-1 level decreased in diabetic postmenopausal women but those women with osteoporosis showed a great decline by about 60%. IGF-1 level in osteoporotic diabetic postmenopausal women was correlated with BMD and most bone turnover markers (OPG, sRANKL, OPG/sRANKL). Osteocalcin declined significantly only in those women with osteoporosis not without osteoporosis. Conclusions: The circulating levels of OPG and sRANKL were not useful markers for bone status in postmenopausal women while the circulating levels of IGF-1 and osteocalcin might give useful information about bone status in postmenopausal diabetic women.

EFFECT OF ACUPUNCTURE ON SERUM INTERLUKIN-6 IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

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.

Correlation of serum total bilirubin content with bone metabolism and micro-inflammatory response in patients with postmenopausal osteoporosis

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.

Relationship between peroxiredoxins protein family levels and osteoporosis in postmenopausal woman

Objective:To observe the expression levels of the main molecules of peroxiredoxins (Prdxs) protein family (Prdx1, Prdx2, Prdx4 and Prdx6) in women with postmenopausal osteoporosis (PMOP), and to analyze their clinical diagnostic values.Methods: Patients diagnosed with PMOP in Hubei Provincial Hospital of Traditional Chinese Medicine and Wuhan Hospital of Traditional Chinese Medicine from May 2016 to March 2018 were included as the study group (72 cases), postmenopausal women with normal bone mineral density (BMD) in the same period were also collected as the control group (51 cases). Levels of Prdx1, Prdx2, Prdx4 and Prdx6 in plasma were determined by ELISA. mRNA levels of Prdx1, Prdx2, Prdx4 and Prdx6 in peripheral blood mononuclear cells (PBMC) were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The correlations between Prdxs and clinical parameters were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic values of Prdxs for PMOP.Results: Prdx1, Prdx4 and Prdx6 levels in the study group were significantly lower than those in the control group (P<0.05). The mRNA expression levels of Prdx1 and Prdx6 of PBMC in the study group were significantly lower than those in the control group (P<0.05). Several Prdxs protein levels (plasma) or mRNA levels (PBMC) in the study group were significantly correlated with lipid levels or inflammatory markers levels (P<0.05). The area under the curve (AUC) of plasma Prdx6 for diagnosing PMOP was 0.794 (95% CI =0.714-0.874). And the AUC of mRNA relative expression of Prdx6 in PBMC for diagnosing PMOP was 0.725 (95% CI =0.635-0.814).Conclusion: The decreased expression of Prdxs protein family (especially Prdx1 and Prdx6) is closely related to the incidence of PMOP, and the decreased Prdxs protein family may promote the occurrence of osteoporosis through the abnormal lipid metabolism pathway and the increased systemic inflammation pathway. The detections of Prdx6 levels in plasma and PBMC are of good diagnostic values for PMOP.

Network pharmacological study of Zuogui pill and Yougui pill for the treatment of postmenopausal osteoporosis

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.

藤黄健骨胶囊对PMOP大鼠RANKL/c-Fos/NFATc1通路的影响

目的探讨免疫调节分子IL-33对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)模型鼠RANKL/c-Fos/NFATc1信号轴的调控作用及藤黄健骨胶囊(Tenghuang Jiangu capsule,TJC)的干预机制。方法构建PMOP大鼠模型,设置假手术组、PMOP模型组、阳性对照组(0.09 mg/kg)和TJC高、中、低剂量组(0.36、0.18、0.09 g/kg),灌胃给药,每天1次,持续8周。从大鼠末次给药后体质量、骨密度(bone mineral density,BMD)及股骨组织微结构等方面评价TJC的疗效;通过ELISA分析TJC对大鼠血清免疫调节因子IL-33、IL-1、IL-31变化;运用qPCR和Western blotting分析TJC对大鼠股骨OPG、RANKL、RANK、c-Fos、NFATc1表达量的影响。结果与假手术组相比,PMOP模型组大鼠的体质量、骨髓脂肪组织相对面积(relative area of bone marrow adipose tissue,BMAT),IL-1、IL-31变化,RANKL、RANK、c-Fos、NFATc1的表达均出现了明显升高的趋势,而BMD、IL-33变化、OPG的表达则出现了明显下降的趋势(P<0.01);与PMOP模型组相比,TJC高剂量组大鼠体质量出现显著下降趋势、IL-33变化出现显著升高趋势(P<0.01),TJC中、高剂量组大鼠BMAT、RANK的表达出现显著下降趋势、OPG的表达出现显著升高趋势(P<0.05或P<0.01),TJC各剂量组大鼠IL-1、IL-31变化,RANKL、c-Fos、NFATc1出现显著降低趋势,BMD出现显著增加趋势(P<0.05或P<0.01)。结论TJC能够提高PMOP大鼠免疫调控分子IL-33含量,抑制免疫调控分子IL-1、IL-31含量和破骨细胞分化标志分子NFATc1的表达,其机制可能与RANKL/c-Fos/NFATc1抑制骨代谢通路密切相关。

香砂六君子汤激活Wnt/β-catenin信号通路促进成骨分化防治PMOP的机制研究

目的 由Hedgehog信号通路探讨补肾方药左归丸对卵巢切除所致骨质疏松症(osteoporosis, OP)大鼠的作用机理。方法 选用雌性SD大鼠,随机分为空白对照组、假手术组、造模组。造模组切除双侧卵巢,假手术组不切除卵巢,仅切除卵巢周围少量脂肪组织。12周后,将造模组随机分为卵巢切除组(OVX组)、阳性对照组和左归丸组。阳性对照组灌服戊酸雌二醇混悬液,左归丸组灌服左归丸水煎液,OVX组灌服等体积纯水,给药13周后取材。通过Micro-CT检测各组骨密度(bone mineral density, BMD),免疫组化法(immunohistochemistry, IHC)检测各组胫骨骨髓基质细胞中Ihh、Ptch、Smo、Gli1、OPG、RANKL的蛋白表达。结果 假手术组骨密度(bone mineral density, BMD)高于OVX组、阳性对照组、左归丸组,且OVX组BMD较阳性对照组、左归丸组更低;OVX组Hedgehog信号通路关键因子Ihh、Ptch、Smo、GLi1蛋白表达水平以及RANKL/OPG比值较假手术组明显增高;阳性对照组和左归丸组Ihh、Ptch、Smo、GLi1蛋白表达水平及RANKL/OPG比值均低于OVX组,但仍高于假手术组。结论 左归丸可抑制卵巢切除所致的Hedgehog信号通路异常活跃,使其关键因子Ihh、Ptch、Smo、GLi1蛋白表达水平明显降低;进而降低RANKL/OPG比值,抑制破骨细胞(osteoclast, OC)活性,减少骨量流失。

六味地黄汤对PMOP模型大鼠股骨MAPK通路动态干预研究

目的研究六味地黄汤对PMOP模型大鼠股骨MAPK信号通路中p38、ERK1/2磷酸化蛋白及mRNA表达的动态干预作用及其机理。方法将6~8月龄未孕雌性SD大鼠(SPF级)编号、称重后随机分为5组,除空白组外,其余各组均采用去卵巢法造模。造模后第5天开始,连续给药90 d。分别在术后30、60、90 d,双能X线骨密度仪检测各组大鼠股骨骨密度;蛋白免疫印迹法(Western blot)法检测各组大鼠股骨中p-p38及p-ERK1/2表达;实时荧光定量PCR(RT-qPCR)法检测各组大鼠股骨中p38、ERK1/2 mRNA表达。结果与空白组比较,模型组大鼠的股骨骨密度值在60、90 d时下降(P<0.05);与模型组比较,六(酒)可上调PMOP术后30、60、90 d模型大鼠股骨中p-p38、p-ERK1/2及ERK1/2 mRNA表达(P<0.05、P<0.01)以及术后60、90 d模型大鼠股骨p38 mRNA表达(P<0.01),而六(生)仅能调整术后90 d模型大鼠股骨中p-p38及p-ERK1/2及mRNA表达(P<0.05、P<0.01)及术后30、60 d模型大鼠股骨中p-ERK1/2表达(P<0.05)。结论六(酒)、六(生)均可干预绝经后骨质疏松症,其机理可能与该汤通过调控MAPK通路中p38及ERK1/2两个蛋白,并使其发生磷酸化修饰,激活成骨相关因子,升高BMD,改善PMOP有关;其中六(酒)的干预作用从绝经早期、中期开始。

The Effect of Acupuncture on Bone Mineral Density in Postmenopausal Women

According to the TCM theory that the kidney is in charge of the bone, the authors carried out a study on the effect of acupuncture on bone mineral density in 40 postmenopausal women with osteoporosis treated by the method of reinforcing the kidney to strengthen the bone, with satisfactory therapeutic results reported as follows.……

Impact of physical activity on health-related quality of life in osteoporotic and osteopenic postmenopausal women:A systematic review

Objective:This meta-analysis included papers which evaluated the effects of physical activity on the health-related quality of life(HRQoL)of osteoporotic and osteopenic postmenopausal women.Methods:Four English databases were searched for relevant randomized clinical trials(RTCs)published from 1970 to June,2014.Eligible RCTs which used the Quality of Life Questionnaire of the European Foundation for Osteoporosis(QUALEFFO)as their outcome measure were selected for inclusion.Results:Five RCTs were included in the final meta-analysis.The results showed that physical activity produced favorable effects in the HRQoL domains of physical function(p=0.001)and pain(p=0.01),but not in other domains.Compared with a single exercise,combined exercise produced more favorable effects on both physical function(p=0.0004)and pain(p=0.02).Short-term physical activity produced significant favorable results in all general health domains of HRQoL(p=0.01),whereas middle-term physical activity produced significant improvements only in the physical function(p<0.01)domains of HRQoL.Long-term physical activity produced significant improvement only in the pain domains of HRQoL(p<0.01),and only in the physical activity group when compared with a control group.Conclusion:Only weak evidence supports the notion that physical activity effectively improves the health-related quality of life of osteoporotic and osteopenic postmenopausal women.Compared with a single exercise,combined exercise produced favorable effects on both physical function and pain.However,different lengths of exercise produced improvements in different domains.