Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17ß-estradiol (E2, 50 µg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of ß-C-terminal telopeptide of type I collagen (ß-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. CONCLUSION: ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Development and Validation of a New Clinical Diagnostic Screening Model for Osteoporosis in Postmenopausal Women.

BACKGROUND: Age and weight are not only strong predictive parameters for osteoporosis diagnosis but can also be easily acquired from patients. This study aimed to develop and validate a new diagnostic screening model for postmenopausal osteoporosis that uses only 2 parameters, viz., age and weight. The discriminative ability of the model was analyzed and compared with that of the osteoporosis self-assessment tool for Asians (OSTA) index. METHODS: The age-weight diagnostic screening model was developed using a retrospective chart review of postmenopausal women aged ≥50 years who underwent dual energy X-ray absorptiometry at a tertiary hospital from November 2017 to April 2022. Logistic regression analysis was used to derive a diagnostic screening model for osteoporosis. RESULTS: A total of 533 postmenopausal women were included in the study. According to the highest Youden index value, a probability cut-off value of 0.298 was used in the diagnosis screening model at any site, which yielded a sensitivity of 84.3% and a specificity of 53.8%. For increased sensitivity as a screening tool, a cut-off value of 0.254 was proposed to obtain a sensitivity of 90.2% and a specificity of 42.2%. The area under receiver operating characteristic curves from all screening models were significantly higher than those from the OSTA index model (p<0.05). CONCLUSIONS: This study showed the feasibility of a postmenopausal osteoporosis diagnostic screening model that uses 2 strong predictors for osteoporosis diagnosis: age and weight. This age-weight diagnostic model is a simple, effective option in postmenopausal osteoporosis screening.

Association of Serum 25-Hydroxyvitamin D and Chronic Periodontitis in Postmenopausal Women after Non-Surgical Periodontal Therapy.

Objectives: Vitamin D deficiency appears to have a major effect on periodontal tissue health. The present study aimed to assess the association of the serum level of 25-hydroxyvitamin D and chronic periodontitis in postmenopausal women. Materials and Methods: This research was done on 30 postmenopausal women with chronic periodontitis who all had at least 20 natural teeth. Intravenous blood samples were taken from the study population at baseline and after completion of non-surgical periodontal treatment. This was followed by assessment of serum levels of 25-hydroxyvitamin D. Next, clinical parameters of all teeth except for third molars were measured, which included pocket depth (PD), gingival index (GI), and plaque index (PI). Data were analyzed by paired t-test and its non-parametric equivalent, the Wilcoxon test. P<0.05 was considered significant. Results: The mean PD, PI and GI before and after the intervention were significantly different (P<0.05). There was, however, no significant difference between the mean vitamin D concentrations before and after treatment (P>0.05). Conclusion: According to the results obtained in the present study, there is no association between serum vitamin D concentrations and chronic periodontitis in postmenopausal women.

Do dental implants placed in patients with osteoporosis have higher risks of failure and marginal bone loss compared to those in healthy patients? A systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare the dental implant survival rate and marginal bone loss between patients with and without osteoporosis. MATERIALS AND METHODS: This systematic review was registered in PROSPERO (CRD42022356377). A systematic search was performed using five databases: MEDLINE/PubMed, Web of Science, Scopus, Embase, and ProQuest for articles published up to July 2022. Additional searches in ClinicalTrials.gov and the reference lists of included studies were performed. The eligibility criteria comprised observational studies with a direct comparison between patients with and without osteoporosis, with a minimum follow-up of 1 year and 10 implants placed in each group, which consider data analysis based on implant level, without restrictions on period or language of publication. The meta-analysis was performed using RevMan 5.4 program. Risk of bias analysis of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Twelve studies met the eligibility criteria, totaling 1132 patients with a mean age range from 54 to 76.6 years. Most of the included patients were women (73.6%). A total of 3505 implants were evaluated-983 in patients with osteoporosis and 2522 in patients without osteoporosis. The meta-analysis indicated no difference in implant survival rates between patients with and without osteoporosis (OR, 1.78; 95% confidence interval [CI], 0.86-3.70; P = 0.12). However, significant bone loss was observed around dental implants placed in patients with osteoporosis (SMD, 0.71 mm; 95% CI, 0.06-0.87 mm). The NOS indicated a low risk of bias in the studies included. However, the certainty of the evidence was classified as very low and low for implant survival rates and bone loss, respectively. CONCLUSION: According to the limitations of the present review, the data suggest that dental implants are a viable treatment option for the rehabilitation of patients with osteoporosis. However, clinical care by professionals is necessary to ensure the maintenance of peri-implant bone stability, as these patients may be susceptible to increased bone loss.

Best Laboratory Screening in Diagnosing Secondary Osteoporosis and Fracture Risk Assessment Tool and the National Osteoporosis Guideline Group Performance in Determining Clinical Risk: A Cross-Sectional Evaluation of the Bone Health in Postmenopausal Brazilian Women.

BACKGROUND: Identifying postmenopausal women with a high risk of having osteoporosis and fractures is a current challenge. This study aimed to assess the diagnostic performance of biochemical tests in identifying secondary osteoporosis and the fracture risk assessment tool (FRAX) in identifying fracture risk. METHODS: Data from biochemical tests and bone densitometry of postmenopausal women were analyzed. Additionally, the FRAX result was obtained and the patients were classified according to the National Osteoporosis Guideline Group (NOGG). RESULTS: A total of 646 women were evaluated, of whom 201 (31.1%) had osteoporosis or a previous frailty fracture. These women had statistically different parathyroid hormone (PTH) and alkaline phosphatase serum levels (p<0.01 and p=0.02, respectively) than those without osteoporosis or fracture. However, those at high risk had a higher prevalence of hypovitaminosis D (46% vs. 36%) and hypocalciuria (17% vs. 9%). The FRAX showed an area under the curve of 0.757 (p<0.01) and 0.788 (p<0.01) for identifying women at risk for "major fractures" and "hip," respectively. The NOGG categorization had a sensitivity of 19% to identify high-risk women, a specificity of 91.3% for low-risk women, with a positive predictive value of 57.4% and a negative predictive value of 64.6%. CONCLUSIONS: The evaluation of PTH, 25-hydroxy-vitamin D, serum calcium, and 24-hr urinary calcium proved adequate for initial osteoporosis screening. The FRAX tool has a regular ability to screen women at risk for fracture, and the NOGG method has high specificity to identify those at low risk.

Trabecular Bone Score and Central Quantitative Computed Tomography for the Prediction of Vertebral Fragility Fractures in Postmenopausal Women.

BACKGROUND: We aimed to investigate whether densitometry results and volumetric bone mineral density (vBMD) can predict vertebral fragility fractures (VFF) in postmenopausal women. METHODS: We enrolled 271 postmenopausal women aged >45 years who visited our hospital for health check-ups between September 2016 and September 2017. The lumbar spine (LS) and femoral neck (FN) densitometry results and trabecular bone score (TBS) were calculated using dual energy X-ray absorptiometry. vBMD was assessed using central quantitative computed tomography (cQCT). Baseline and follow-up X-ray images were reviewed to evaluate thoracolumbar vertebral compression fractures (CFs), according to the Genant criteria. RESULTS: At baseline, 76 patients (28.0%) had CF. Additional or progressive fractures were noted in 26 participants (9.6%) with a median follow-up of 19.5 months. The median TBS and cQCT were significantly higher in participants without baseline CF than those with baseline CF (p<0.001). During the follow-up, Kaplan-Meier analysis showed that T-scores of the LS and FN <-2.5, degraded microarchitecture based on the TBS (≤1.200), and vBMD <80 mg/cm3 was significantly associated with future osteoporotic CF. The final multivariate Cox regression analysis showed that baseline CF and low TBS and vBMD were significant risk factors for future VFF. CONCLUSIONS: Participants with baseline CF and degraded microarchitecture had higher CF predisposition. Moreover, cQCT can predict future vertebral fractures.

Expression of CircRNA_0048211 and its correlation with bone metabolic markers in patients with postmenopausal osteoporosis / 中华骨科杂志

Objective:To investigate the diagnostic value of serum CircRNA_0048211 expression level in postmenopausal osteoporosis (PMOP) and its correlation with bone-specific alkaline phosphatase (BALP), osteopontin (OPN), procollagen type I N-terminal propeptide (PINP) and β-crosslaps (β-CTX). Methods:Data of postmenopausal women who underwent physical examination in our hospital from January 2019 to December 2021 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry and divided into PMOP group, decreased bone mass group and normal bone mass group according to BMD level. The serum CircRNA_0048211, BALP, OPN, PINP and β-CTX levels were compared in each group. Binary logistic regression was used to analyze the risk factors of PMOP, the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of CircRNA_0048211, BALP, OPN, PINP and β-CTX on PMOP. The correlation between CircRNA_0048211 expression level and BALP, OPN, PINP and β-CTX was analyzed by Pearson correlation analysis. Results:A total of 218 patients were included in this study. Age is 60.52±6.83 years (range, 47-76 years), body mass index is 24.27±2.28 kg/m 2 (range, 22.18-25.73 kg/m 2) and menopausal time is 10.16±4.25 years (range, 2.30-21.80 years). There were 40 cases in PMOP group, 97 cases in osteopenia group and 81 cases in normal bone mass group. The serum CircRNA_ 0048211, BALP, OPN, PINP and β-CTX was significantly different between PMOP group, osteopenia group and normal group ( F=21.15, P<0.001; F=12.52, P<0.001; F=17.86, P<0.001; F=14.32, P<0.001; F=15.52, P<0.001). The serum CircRNA_0048211 level in PMOP group (0.37±0.08) were significantly lower than that of osteopenia group (1.05±0.46) and normal bone mass group (1.73±0.81), the difference was statistically significant ( P<0.05). The levels of BALP (28.42±7.35 μg/L), OPN (17.28±7.30 ng/ml), PINP (58.40±14.37 ng/ml) and β-CTX (1.52±0.28 μg/L) in PMOP group were significantly higher than those in osteopenia group (22.61±5.93 μg/L, 11.95±5.64 ng/ml, 49.16±11.24 ng/ml, 0.81±0.17 μg/L) and normal bone mass group (16.30±4.18 μg/L, 7.62±3.25 ng/ml, 35.48±7.12 ng/ml, 0.37±0.10 μg/L), the difference was statistically significant ( P<0.05). Binary logistic regression analysis showed that decreased CircRNA_0048211 expression level [ OR=3.53, 95% CI (2.73, 10.32)] was a risk factor for the occurrence of PMOP ( P<0.001). ROC curve showed that CircRNA_0048211≤0.76 has a diagnostic significance on PMOP, and its combination of BALP, OPN, PINP and β-CTX has the highest AUC [0.95, 95% CI (0.89, 1.00)] in diagnosing PMOP. Correlation analysis showed that CircRNA_0048211 expression level were negatively correlated with BALP, OPN, PINP and β-CTX ( r=-0.46, P<0.001; r=-0.80, P<0.001; r=-0.81, P<0.001; r=-0.69, P<0.001). Conclusion:The CircRNA_0048211 showed low expression in PMOP, which was negatively correlated with BALP, OPN, PINP and β-CTX. The combination of these five factors has certain clinical value in the diagnosis of PMOP.

Effect of Lactobacillus Fermentum as a Probiotic Agent on Bone Health in Postmenopausal Women.

BACKGROUND: Probiotics are live microorganisms that confer health benefits on the host. Many animal studies have shown that among the probiotics, lactobacilli exert favorable effects on bone metabolism. Herein, we report the results of a randomized controlled trial performed to investigate the effect of Lactobacillus fermentum (L. fermentum) SRK414 on bone health in postmenopausal women. METHODS: The bone turnover markers (BTMs) and bone mineral density (BMD) in participants in the study group (N=27; mean age, 58.4±3.4 years) and control group (N=26; mean age, 59.5±3.4 years) were compared during a 6-month trial. BTMs were measured at pretrial, 3 months post-trial, and 6 months post-trial, while BMD was measured at pre-trial and 6 months post-trial. Changes in the gut microorganisms were also evaluated. RESULTS: Femur neck BMD showed a significant increase at 6 months post-trial in the study group (P=0.030) but not in the control group. The control group showed a decrease in osteocalcin (OC) levels (P=0.028), whereas the levels in the study group were maintained during the trial period. The change in L. fermentum concentration was significantly correlated with that in OC levels (r=0.386, P=0.047) in the study group at 3 months post-trial. CONCLUSIONS: Probiotic (L. fermentum SRK414) supplementation was found to maintain OC levels and increase femur neck BMD during a 6-month trial in postmenopausal women. Further studies with a larger number of participants and a longer study period are required to increase the utility of probiotics as an alternative to osteoporosis medication.

Osteoporosis postmenopáusica: relevancia de la búsqueda estructurada de causas secundarias / A search for secondary causes of osteoporosis or low mineral density in postmenopausal women

BACKGROUND: A secondary cause can be found in up to one third of women with osteoporosis, potentially modifying their therapeutic approach. AIM: To determine the prevalence of secondary causes and risk factors for decreased bone mineral density (BMD) and osteoporosis. Material and Methods: We included postmenopausal women with a diagnosis of osteoporosis or low BMD who consulted for the first time in an endocrinology clinic between October 2018 and March 2020. A complete medical history, physical examination and a standardized laboratory assessment to identify secondary causes were performed. RESULTS: During the study period, 114 women were evaluated, 30 of them with low BMD and 84 with osteoporosis. After obtaining a medical history and a structured laboratory screening, at least one secondary cause was found in 50% of patients with osteoporosis and in 67% of those with low BMD. Most patients with no identified secondary cause had at least one risk factor for fragility fractures. Conclusions: A structured evaluation that includes medical history and standardized laboratory study in postmenopausal women with osteoporosis or low BMD, is a valuable tool to identify secondary causes of osteoporosis.

Effects of high-intensity multi-modal exercise training (HIT-MMEX) on bone mineral density and muscle performance in postmenopausal women. A Pilot randomized controlled trial.

Objectives: To determine the effects of high-intensity multimodal exercise training on bone mineral density and muscle performance in postmenopausal women. METHODS: The two-armed, parallel, pilot randomised controlled trial was conducted from November 2020 to July 2021 at Riphah Rehabilitation Centre, Rawalpindi, Pakistan, and comprised women aged 45-70 having been in the post-menopause phase for at least 3 years, with body mass index <30, community ambulant and willing to have exercise therapy. The subjects were randomised into two equal groups. The experimental group A received supervised high-intensity resistance, weight-bearing, balance and mobility training twice weekly for 8 months. The control group B received low-to-moderate intensity exercises. Femoral neck and lumbar spine bone mineral density (g/cm2) were taken through a dual-energy X-ray absorptiometry scan. Muscle performance was measured using 1 repetition maximum for leg and trunk extensors, and 30 sec sit to stand test. Data was analysed using SPSS 21. RESULTS: Of the 101 women screened, 28(27.7%) were enrolled; 14(50%) in group A having mean age 53.36±6.28 years, and 14(50%) in group B having mean age 51.71±4.82 years (p>0.05). Group A showed significantly more improvement than group B both with respect to lumbar spine bone mineral density and muscle performance (p<0.05). CONCLUSIONS: Supervised high-intensity multimodal exercise training protocol had a positive effect on lumbar spine bone mineral density and muscle performance in postmenopausal women. Clinical Trial Number: NCT04653350, Link https://clinicaltrials.gov/ct2/show/NCT04653350.

Association between serum lipid profile, body mass index and osteoporosis in postmenopausal Sudanese women

Background: Epidemiological observations suggest links between osteoporosis and the risk of acute cardiovascular events. Whether the two clinical conditions are linked by common pathogenic factors or atherosclerosis per se remains incompletely understood. The reduction of bone density and osteoporosis in postmenopausal women contributes to elevated lipid parameters and body mass index (BMI). Objective: To investigate the relationship between serum lipid profile, BMI and osteoporosis in postmenopausal women. Materials and Methods: A prospective analytical case control-study conducted in Khartoum north hospital at Khartoum city, capital of the Sudan from April 2017 to March 2018 after ethical approval obtained from the local Research Ethics Committee of Faculty of Medical Laboratories, Alzaeim Alazhary University on the committee meeting number (109) on Wednesday 15th February 2017. A written informed consent was obtained from all participants to participate in the study.Two hundred postmenopausal women were enrolled in the study. The age was studied in one hundred osteoporosis postmenopausal women as a case group and one hundred non-osteoporosis postmenopausal women as control group. The serum lipid profiles were estimated using spectrophotometers (Mandry) and BMI calculated using Quetelet index formula. The data were analysed using SPSS version 16. Results: The BMI, serum total cholesterol, triglyceride, HDL and LDL in case group respectively were (24.846±2.1647, 251.190±27.0135 mg/dl, 168.790 ±45.774 mg/dl, 50.620 ± 7.174 mg/dl, 166.868 ±28.978 mg/dl). While the BMI, serum total cholesterol, triglyceride, HDL and LDL in control group respectively were (25.378 ±3.8115, 187.990 ± 26.611 mg/dl, 139.360±20.290 mg/dl, 49.480 ±4.659 mg/dl, 111.667 ±28.0045 mg/dl). All serum lipid profiles significantly increased (p=0.000) in the case group compared to the control group, except serum HDL was insignificant different between the case and control group and also BMI was insignificant different between the case and control group. There was a positive Pearson's correlation between BMD and serum total cholesterol (r= 0.832, P<0.01), serum LDL (r = 0.782, P<0.01) and serum triglyceride (r = 0.72, P<0.01). Conclusions: Osteoporotic postmenopausal women had a significant increase in serum lipid profile and BMI. Moreover, we found a positive link between women with cardiovascular diseases and stroke

Effects of cardiovascular health behaviors and factors on postmenopausal osteoporosis in Suxichang area of Jiangsu province / 中华老年医学杂志

Objective:To explore the relationship of cardiovascular health behavior and factors with development of bone mass loss and postmenopausal osteoporosis in Suxichang area of Jiangsu province.Methods:In the across sectional study, a total of 2 423 postmenopausal women receiving health check-up from March 2019 to June 2020 in our hospital were enrolled.The seven variable factors included cardiovascular health behavior(body mass index, exercise, healthy diet and smoking state)and cardiovascular health-influencing factors(blood pressure, fasting blood glucose and total cholesterol). The information of the seven factors and bone mineral density were recorded.The seven factors were classified as ideal, average and poor, according to the level of bone mineral density.All individuals were divided into three groups: normal bone mass(n=1 305), osteopenia(n=290)and osteoporosis(n=828).Results:There were statistically significant differences in age, fasting blood glucose, systolic blood pressure, diastolic blood pressure, total cholesterol and exercise between osteoporosis and normal bone mass group( P<0.05). As the number of ideal cardiovascular health behaviors and factors increased, the proportion of bone mass loss and osteoporosis gradually decreased( P<0.05). Multiple logistic regression analysis showed that ageing, increased total cholesterol and fasting blood glucose levels were the independent risk factors of osteoporosis.The exercise and normal body mass index were the protective factors for osteoporosis.For each 1 unit increment in age, total cholesterol, body mass index and fasting blood glucose, the OR values for bone mineral density decrement by 1 grade were 1.17, 1.25, 0.92 and 1.23, respectively(all P<0.05). The OR value for bone mineral density decrement by 1 grade was 0.58( P<0.05)when exercise decreased by 1 grade. Conclusions:Postmenopausal women should positively control the levels of total cholesterol and fasting blood glucose, maintain reasonable body weight and conduct regular exercise, which are conductive to the prevention and treatment of postmenopausal osteoporosis.

Early numerical rating scale and Oswestry disability index in postmenopausal osteoporosis treated with denosumab / 中华骨科杂志

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.

Expression and the relative mechanisms of circular RNA hsa_circ_0001445 in patients with postmenopausal osteoporosis / 中华老年医学杂志

Objective:To investigate the clinical significance and regulatory molecular mechanism of the circular RNA(circRNA)hsa_circ_0001445 in postmenopausal osteoporosis(PMOP).Methods:RNA was extracted from clinically collected blood samples, and the expression of circRNA hsa_circ_0001445 was detected by quantitative real-time PCR(qRT-PCR). Luciferase reporter gene analysis and RNA pull-down experiments were performed to investigate the interaction between two genes.Results:Compared with healthy controls, the plasma circRNA hsa_circ_0001445 in PMOP patients was down regulated( P<0.001). The circRNA hsa_circ_0001445 distinguished PMOP patients from healthy controls with high sensitivity and specificity.The area under the ROC curve(AUC)was 0.9654(95% CI: 0.9361-0.9947, P<0.001), and the sensitivity was 94.0%, while the specificity was 88.0%.The circRNA hsa_circ_0001445 promoted the osteogenic differentiation and inhibited the adipogenic differentiation of hBMSCs.The circRNA hsa_circ_0001445 can directly bind to miR-127-5p. Conclusions:Plasma level of the circRNA hsa_circ_0001445 is a potential diagnostic biomarker of PMOP and regulates the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-127-5p.

A randomized double-blinded placebo-controlled clinical trial of minodronate tablet in postmenopausal Chinese women with osteoporosis / 中华妇产科杂志

Objective:To verify the efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis.Methods:In this randomized, double-blinded, placebo-controlled trial, 262 postmenopausal women were enrolled. Patients were randomized to receive daily oral minodronate 1 mg with supplements of 500 mg calcium and 200 U vitamin D 3 ( n=130) or placebo ( n=132) with daily supplements of 500 mg calcium and 200 U vitamin D 3, for 48 weeks. The primary endpoint was the average bone mineral density (BMD) change in the lumbar vertebrae 48 weeks post-treatment. Secondary outcome measures was the incidence of vertebral fractures. Safety assessments included the rate of adverse events. Results:At the end of 48 weeks treatment, the average BMD change rate from baseline were: full analysis set results: (3.52±4.82)% in the minodronate group and (2.00±5.74)% in the placebo group; per-protocol set results: (3.99±5.05)% in the minodronate group and (2.07±6.20)% in the placebo group; the differences were all significant (all P<0.05). Vertebral fracture occured in 3 patients (2.3%, 3/132) in the placebo group, and 1 case (0.8%, 1/130) in the minodronate group ( P>0.05). The incidence of adverse events was 71.5% (93/130) in the minodronate group and 78.0% (103/132) in the placebo group ( P>0.05). Conclusion:Minodronate is effective and safe in the treatment of postmenopausal osteoporosis without severe side effects.

Zuogui Wan improves trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats by regulating orexin-A and orexin receptor.

OBJECTIVE: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model. METHODS: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17ß-estradiol (E2, 50 µg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17ß-estrogen (17ß-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis. RESULTS: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17ß-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01). CONCLUSION: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

[Clinical efficacy and radiation exposure analysis of vertebroplasty and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture].

OBJECTIVE: Taking the classic bilateral puncture vertebroplasty as a reference, to evaluate the clinical efficacy of vertebroplasty of the curved-angle puncture device, analyze the radiation exposure of patients and surgeons during the operation and summarize the protective measures. METHODS: The clinical data of 49 patients with osteoporotic vertebral compression fractures admitted from March 2018 to September 2019 were retrospectively analyzed. According to the different surgical puncture methods, 49 patients were divided into vertebroplasty group (using classic bilateral puncture) and curved vertebroplasty group (using curved angle puncture). Among them, there were 26 cases in vertebroplasty group, including 7 males and 19 females, aged (73.25±6.36) years, 2 cases in thoracic segment, 21 cases in thoracolumbar segment, and 3 cases in lumbar segment. In curved vertebroplasty group, there were 23 cases, including 6 males and 17 females, aged (73.09±6.52) years, 3 cases in thoracic segment, 19 cases in thoracolumbar segment, and 1 case in lumbar segment. The operation time and the amount of injected bone cement in the two groups were recorded. Visual analogue scale (VAS) and modified Oswestry Disability Index (ODI) were respectively used to assess the pain degree and lumbar function, the postoperative bone cement leakage or other complications were observed. The radiation doses of the two groups of patients and surgeons were compared. RESULTS: All 49 patients were followed up for 10-22 (14.55±3.83) months. Eleven cases in vertebroplasty group and 9 cases in curved vertebroplasty group occurred bone cement leakage after surgery, and there was no statistically significant difference between two groups. VAS scores of vertebroplasty group were 6.23±0.68 before operation and 1.69±0.47 at 1 day after operation, respectively, modified ODI were (72.59±3.25)% and (33.59±2.85)%. The preoperative and postoperative VAS scores of curved vertebroplasty group were 6.46±0.56 and 1.57±0.49, respectively, modified ODI were (73.21±3.18)% and (33.17±2.37)%. The postoperative pain degree and lumbar function of the two groups were significantly improved, but the difference between the groups was not statistically significant. The operation time of curved vertebroplasty group and vertebroplasty group were (17.27±9.58) min and(23.19±8.56) min, and the amount of injected bone cement were (4.91±1.49) ml and (6.58±1.42) ml. Obviously, curved vertebroplasty group has more advantages in operation time and the amount of injected bone cement. In curved vertebroplasty group, the radiation dose of the operator was (0.53±0.05) mSv and the patient was (10.64±1.65) mSv;in vertebroplasty group, the operator was (0.59±0.08) mSv andthe patient was (13.52±1.81) mSv. The radiation dose of patients in curved vertebroplasty group was significantly lower than that of the vertebroplasty group, but there was no statistically significant difference in the operator between two groups. CONCLUSION: Both puncture methods can achieve satisfactory clinical results, but curved angle puncture can optimize the distribution of bone cement and reduce the radiation dose of patients.

Long-Term Treatment of Postmenopausal Osteoporosis.

Osteoporosis is an incurable chronic condition, like heart disease, diabetes, or hypertension. A large gap currently exists in the primary prevention of fractures, and studies show that an estimated 80% to 90% of adults do not receive appropriate osteoporosis management even in the secondary prevention setting. Case finding strategies have been developed and effective pharmacological interventions are available. This publication addresses how best to use the pharmacological options available for postmenopausal osteoporosis to provide lifelong fracture protection in patients at high and very high risk of fracture. The benefit of osteoporosis therapies far outweighs the rare risks.

Effect of Vitamin K2 Alone or in Combination on Various Bone Turnover Markers Amongst Postmenopausal Females.

BACKGROUND: Osteoporosis is common in postmenopausal women. Some studies have demonstrated the usefulness of vitamin K through the action of bone-specific proteins and osteoblast and osteoclast activities. However, no systematic review had explored this aspect in postmenopausal women. Hence, this systematic review aimed to explore the effect of vitamin K2 alone or in combination with other agents (vitamin D3 or calcium) on various bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women. METHODS: MEDLINE, ScienceDirect, PubMed, and Google Scholar were searched to identify relevant studies using specific inclusion criteria. Data extraction and quality assessment were carried out using standardized tests, and the results were narratively synthesized and presented in the form of tables. RESULTS: Vitamin K2 was beneficial in inducing an improvement or preventing deterioration, as evidenced by the BMD and osteocalcin (OC), undercarboxylated OC (ucOC), carboxylated OC (cOC), and γ-carboxylated OC levels. However, its effect was not conclusive when procollagen type 1 N-terminal propeptide, carboxyterminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen, bone alkaline phosphatase, deoxypyridinoline, and N-terminal telopeptide levels (NTX) and ucOC:cOC or cOC:ucOC, and NTX:creatinine ratios were examined. CONCLUSIONS: Vitamin K2 supplementation combined with vitamin D and calcium was found to be advantageous. However, vitamin K2 supplementation cannot replace the existing treatment options. In addition, vitamin K2 should be used with caution, considering its interactions with food and other drugs.

Curative effect of Wenshen-Gushu Decoction combined with conventional western medicine for the postmenopausal osteoporosis patients with kidney yang deficiency type / 国际中医中药杂志

Objective:To investigate the clinical effect of Wenshen-Gushu Decoction combined with conventional western medicine on postmenopausal osteoporosis patients with kidney yang deficiency type. Methods:A total of 105 postmenopausal osteoporosis patients admitted in Huxi Hospital Affiliated to Jining Medical College from January 2017 to December 2019 were selected. According to the random number table method, they were divided into the control group (52 cases) and observation group (53 cases). The control group was treated with conventional western medicine, and the observation group was treated with self-made Wenshen-Gushu Decoction on the basis of the control group. Both groups were treated for 8 weeks. The TCM Symptom Score, Visual Analogue Scale (VAS), bone mineral density of troch (Troch), bone mineral density of ward’s triangle (ward’s), bone mineral density of L 1-4 and serum levels of steroid hormone receptor coactivator-3 (SRC-3), B-cell lymphoma gene-2 (Bcl-2) and transcription element coactivator (PGC-1a) were compared between two groups before and after treatment. The incidence of adverse reactions in the treatment process was observed, and the clinical efficacy was evaluated. Results:The total effective rate of observation group was 79.3% (42/53), and that of control group was 61.5% (32/52), where the difference between the two groups was statistically significant ( χ2=3.955, P=0.047). After treatment, the scores of lumbar and knee soreness, lumbar and spinal pain, lower limb flaccidity, walking difficulty and the VAS scores in the observation group were significantly lower than those in the control group ( t=21.956, 20.472, 18.591, 13.439, 19.594, 9.035, P<0.001). After treatment, the Troch [(0.70 ± 0.07) g/cm 2vs. (0.67 ± 0.06) g/cm 2, t=2.356] and Ward’s [(0.57 ± 0.06) g/cm 2vs. (0.510 ± 0.05) g/cm 2, t=5.561] and the bone mineral density of L 1-4 [(0.88 ± 0.07) g/cm 2vs. (0.80 ± 0.05) g/cm 2, t=6.727] in the observation group were significantly higher than those in the control group ( P<0.05). The serum levels of SRC-3 [(0.34 ± 0.08) ng/L vs. (0.27 ± 0.07) ng/L, t=4.768], Bcl-2 [(9.56 ± 2.15) μg/L vs. (8.45 ± 2.07) μg/L, t=1.917] and PGC-1a[(0.33 ± 0.06) g/L vs. (0.25 ± 0.04) g/L, t=8.023] in the observation group were significantly higher than those in the control group ( P<0.05). No serious adverse reactions occurred in both groups during the treatment. Conclusion:Wenshen-Gushu Decoction combined with conventional western medicine shows clinical effect and can reduce clinical symptoms, improve bone mineral density, and upregulate the levels of SRC-3, Bcl-2, PGC-1a for the postmenopausal osteoporosis patients with kidney yang deficiency typea with safety.