Osteoporosis and depression in perimenopausal women: From clinical association to genetic causality.

BACKGROUND: Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group. METHODS: The study analyzed NHANES 2007-2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods. RESULTS: The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692-28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699-10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577-6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004-6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013). LIMITATIONS: Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations. CONCLUSION: Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

The immediate effect of cervical rotation-traction manipulation on cervical paravertebral soft tissue: a study using soft tissue tension cloud chart technology.

BACKGROUND: To evaluate the reliability of the Soft Tissue Tension Cloud Chart (STTCC) technology, an original method combining multi-point Cervical Paravertebral Soft Tissue Test (CPSTT) with MATLAB software, we conducted a preliminary analysis on the immediate effects of Orthopaedic Manual Therapy (OMT) on cervical paravertebral soft tissue. METHODS: 30 patients with Cervical Spondylotic Radiculopathy (CSR) were included in this study. We analyzed the differences in CPSTT before and after treatment with Cervical Rotation-Traction Manipulation (CRTM), a representative OMT technique in Traditional Chinese Medicine, using the STTCC technology. RESULTS: The STTCC results demonstrated that post-treatment CPSTT levels in CSR patients were significantly lower than pre-treatment levels after application of CRTM, with a statistically significant difference (P < 0.001). Additionally, pre-treatment CPSTT levels on the symptomatic side (with radicular pain or numbness) were higher across the C5 to C7 vertebrae compared to the asymptomatic side (without symptoms) (P < 0.001). However, this difference disappeared after CRTM treatment (P = 0.231). CONCLUSIONS: The STTCC technology represents a reliable method for analyzing the immediate effects of OMT. CSR patients display uneven distribution of CPSTT characterized by higher tension on the symptomatic side. CRTM not only reduces overall cervical soft tissue tension in CSR patients, but can also balance the asymmetrical tension between the symptomatic and asymptomatic sides. TRIAL REGISTRATION: This study was approved by the Chinese Clinical Trials Registry (Website: . https://www.chictr.org.cn .) on 20/04/2021 and the Registration Number is ChiCTR2100045648.

Effect of Baduanjin exercise on primary osteoporosis: study protocol for randomized controlled trial.

BACKGROUND: Lack of exercise is often a major cause of chronic disease. Osteoporosis (OP) is a chronic disease with multifactorial co-morbidity. Baduanjin (BDJ) exercise may be a powerful tool for modifying risk factors. The aim is to provide more evidence about the effectiveness of BDJ exercise in improving pain and balance ability in patients with OP. METHODS: In the prospective randomized controlled trial, 160 participants will be recruited and randomized to the treatment group (BDJ exercise combined with Calcium carbonate and D3) or the control group (Calcium carbonate and D3) at 1:1 ratio. Participants in the treatment group will receive 24-week BDJ exercise for 30-60 min, 3 times a week, along with Calcium carbonate and D3 at each day, while participants in the control group will receive Calcium carbonate and D3 only. All outcome indicators will be measured at baseline, after the 6th month of treatment and 6th month after the end of treatment. The primary outcomes include pain and balance ability, as measured by the visual analogue scale (VAS) and Berg balance scale (BBS). The secondary outcomes will primarily include bone mineral density (BMD), laboratory tests (including P1NP, ß-CTX, MSTN, FDF-23, NPY), the timed "up and go" (TUG) test, the morse fall scale (MFS), the five-times sit-to-stand test (FTSST). DISCUSSION: The study will hopefully confirm that BDJ exercise, as a non-drug intervention, should be recommended for patients with OP to prevent bone loss, falls and fractures. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN76945140 registered on 07/06/2022.

Effectiveness and safety of manual therapy for knee osteoarthritis: An overview of systematic reviews and meta-analyses.

Background: Manual therapy has been used as an alternative approach to treat knee osteoarthritis (KOA) for many years. Numerous systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its effectiveness and safety. Nevertheless, the conclusions of SRs/MAs are inconsistent, and the uneven quality needs to be critically appraised. Objectives: To conduct a comprehensive overview of the effectiveness and safety of manual therapy for KOA and the quality of relevant SRs/MAs, thus providing critical evidence and valuable direction for future researchers to promote the generation of advanced evidence. Methods: The pre-defined search strategies were applied to eight electronic databases from inception to September 2022. Suitable SRs/MAs were included in accordance with the inclusion and exclusion criteria. The methodological quality, risk of bias, reporting quality, and evidence quality were assessed by two independent reviewers who used respectively the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 Version (PRISMA 2020), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE) based on the method of narrative synthesis. We excluded the overlapping randomized controlled trials (RCTs) and performed a re-meta-analysis of the total effective rate. Results: A total of eleven relevant SRs/MAs were included: nine SRs/MAs were rated critically low quality, and two were rated low quality by AMSTAR-2. According to ROBIS, all SRs/MAs were rated low risk in Phase 1 (assessing relevance) and Domain 1 (study eligibility criteria) of Phase 2. Three SRs/MAs (27.27%) were rated low risk in Domain 2 (identification and selection of studies). Ten SRs/MAs (90.91%) were rated low risk in Domain 3 (data collection and study appraisal). Five SRs/MAs (45.45%) were rated low risk in Domain 4 (synthesis and findings). And five SRs/MAs (45.45%) were rated low risk in Phase 3 (risk of bias in the review). By PRISMA 2020, there were some reporting deficiencies in the aspects of abstract (2/11, 18.18%), search strategy (0/11, 0%), preprocessing of merging data (0/11, 0%), heterogeneity exploration (6/11, 54.55%), sensitivity analysis (4/11, 36.36%), publication bias (5/11, 45.45%), evidence quality (3/11, 27.27%), the list of excluded references (3/11, 27.27%), protocol and registration (1/11, 9.09%), funding (1/11, 9.09%), conflict of interest (3/11, 27.27%), and approach to relevant information (0/11, 0%). In GRADE, the evidence quality was defined as moderate quality (8 items, 21.05%), low quality (16 items, 42.11%), and critically low quality (14 items, 36.84%). Among the downgraded factors, risk of bias, inconsistency, imprecision, and publication bias were the main factors. A re-meta-analysis revealed that manual therapy can increase the total effective rate in KOA patients (risk ratio = 1.15, 95% confidence interval [1.12, 1.18], p < 0.00001; I2 = 0, p = 0.84). There are four reviews that narratively report adverse effects, and no severe adverse reactions occurred in the manual therapy group. Conclusions: Manual therapy may be clinically effective and safe for patients with KOA. However, this conclusion must be interpreted with caution because of the generally unsatisfactory study quality and inconsistent conclusions of the included SRs/MAs. Further rigorous and normative SRs/MAs are expected to be carried out to provide robust evidence for definitive conclusions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier: CRD42022364672.

Real-Time Prediction of Sepsis in Critical Trauma Patients: Machine Learning-Based Modeling Study.

BACKGROUND: Sepsis is a leading cause of death in patients with trauma, and the risk of mortality increases significantly for each hour of delay in treatment. A hypermetabolic baseline and explosive inflammatory immune response mask clinical signs and symptoms of sepsis in trauma patients, making early diagnosis of sepsis more challenging. Machine learning-based predictive modeling has shown great promise in evaluating and predicting sepsis risk in the general intensive care unit (ICU) setting, but there has been no sepsis prediction model specifically developed for trauma patients so far. OBJECTIVE: To develop a machine learning model to predict the risk of sepsis at an hourly scale among ICU-admitted trauma patients. METHODS: We extracted data from adult trauma patients admitted to the ICU at Beth Israel Deaconess Medical Center between 2008 and 2019. A total of 42 raw variables were collected, including demographics, vital signs, arterial blood gas, and laboratory tests. We further derived a total of 485 features, including measurement pattern features, scoring features, and time-series variables, from the raw variables by feature engineering. The data set was randomly split into 70% for model development with stratified 5-fold cross-validation, 15% for calibration, and 15% for testing. An Extreme Gradient Boosting (XGBoost) model was developed to predict the hourly risk of sepsis at prediction windows of 4, 6, 8, 12, and 24 hours. We evaluated model performance for discrimination and calibration both at time-step and outcome levels. Clinical applicability of the model was evaluated with varying levels of precision, and the potential clinical net benefit was assessed with decision curve analysis (DCA). A Shapley additive explanation algorithm was applied to show the effect of features on the prediction model. In addition, we trained an L2-regularized logistic regression model to compare its performance with XGBoost. RESULTS: We included 4603 trauma patients in the study, 1196 (26%) of whom developed sepsis. The XGBoost model achieved an area under the receiver operating characteristics curve (AUROC) ranging from 0.83 to 0.88 at the 4-to-24-hour prediction window in the test set. With a ratio of 9 false alerts for every true alert, it predicted 73% (386/529) of sepsis-positive timesteps and 91% (163/179) of sepsis events in the subsequent 6 hours. The DCA showed our model had a positive net benefit in the threshold probability range of 0 to 0.6. In comparison, the logistic regression model achieved lower performance, with AUROC ranging from 0.76 to 0.84 at the 4-to-24-hour prediction window. CONCLUSIONS: The machine learning-based model had good discrimination and calibration performance for sepsis prediction in critical trauma patients. Using the model in clinical practice might help to identify patients at risk of sepsis in a time window that enables personalized intervention and early treatment.

Subcutaneous Adipose Tissue Is Associated with Acute Kidney Injury after Abdominal Trauma Based on the Generalized Propensity Score Approach: A Retrospective Cohort Study.

INTRODUCTION: Obesity is associated with an increased risk of acute kidney injury (AKI) after trauma. However, the associations between different adipose tissue depots and AKI remain unknown. Our study aimed to quantify the effect of abdominal adiposity on AKI in trauma patients. METHODS: We performed a retrospective cohort study of abdominal trauma patients who were admitted to our hospital from January 2010 to March 2020. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured at the level of the third lumbar vertebra using computed tomography. Causal modeling based on the generalized propensity score was used to quantify the effects of body mass index (BMI), VAT, and SAT on AKI. RESULTS: Among 324 abdominal trauma patients, 67 (20.68%) patients developed AKI. Patients with AKI had higher BMI (22.46 kg/m2 vs. 22.04 kg/m2, p = 0.014), higher SAT areas (89.06 cm2 vs. 83.39 cm2, p = 0.151), and higher VAT areas (140.02 cm2 vs. 91.48 cm2, p = 0.001) than those without AKI. By using causal modeling, we found that the risk of developing AKI increased by 8.3% (p = 0.001) and 4.8% (p = 0.022) with one unit increase in BMI (per 1 kg/m2) and ten units increase in SAT (per 10 cm2), respectively. However, VAT did not show a significant association with AKI (p = 0.327). CONCLUSION: SAT, but not VAT, increased the risk of AKI among abdominal trauma patients. Measurement of SAT might help identify patients at higher risk of AKI.

Longitudinal D-Dimer Trajectories and the Risk of Mortality in Abdominal Trauma Patients: A Group-Based Trajectory Modeling Analysis.

This study aimed to identify the long-term D-dimer trajectory patterns and their associations with in-hospital all-cause mortality in abdominal trauma patients. This is a retrospective cohort study of general adult abdominal trauma patients admitted to Jinling Hospital (Nanjing, China) between January 2010 and April 2020. Group-based trajectory modeling was applied to model D-dimer trajectories over the first 50 days post-trauma. A multivariable logistic regression was performed to estimate the associations between D-dimer trajectories and in-hospital all-cause mortality. A total of 309 patients were included. We identified four distinct D-dimer trajectories: group 1 (57.61%; "stable low"), group 2 (28.16%; "moderate-decline"), group 3 (8.41%; "high-rapid decline"), and group 4 (5.83%; "high-gradual decline"). The SOFA score (p = 0.005) and ISS (p = 0.001) were statistically higher in groups 3 and 4 than in groups 1 and 2. The LMWH and UFH did not differ between groups 3 and 4. Compared with the patients in group 1, only the patients in group 4 were at a higher risk of in-hospital all-cause mortality (OR = 6.94, 95% CI: 1.20-40.25). The long-term D-dimer trajectories post-trauma were heterogeneous and associated with mortality. An initially high and slowly-resolved D-dimer might function as the marker of disease deterioration, and specific interventions are needed.

High Fat-to-Muscle Ratio Was Associated with Increased Clinical Severity in Patients with Abdominal Trauma.

Overweight and moderate obesity confer a survival benefit in chronic diseases such as coronary artery disease and chronic kidney disease, which has been termed the "obesity paradox". However, whether this phenomenon exists in trauma patients remains controversial. We performed a retrospective cohort study in abdominal trauma patients admitted to a Level I trauma center in Nanjing, China between 2010 and 2020. In addition to the traditional body mass index (BMI) based measures, we further examined the association between body composition-based indices with clinical severity in trauma populations. Body composition indices including skeletal muscle index (SMI), fat tissue index (FTI), and total fat-to-muscle ratio (FTI/SMI) were measured using computed tomography. Our study found that overweight was associated with a four-fold risk of mortality (OR, 4.47 [95% CI, 1.40-14.97], p = 0.012) and obesity was associated with a seven-fold risk of mortality (OR, 6.56 [95% CI, 1.07-36.57], p = 0.032) compared to normal weight. Patients with high FTI/SMI had a three-fold risk of mortality (OR, 3.06 [95% CI, 1.08-10.16], p = 0.046) and double the risk of an intensive care unit length of stay ≥ 5 d (OR, 1.75 [95% CI, 1.06-2.91], p = 0.031) compared to patients with low FTI/SMI. The obesity paradox was not observed in abdominal trauma patients, and high FTI/SMI ratio was independently associated with increased clinical severity.

Ferroptosis and musculoskeletal diseases: "Iron Maiden" cell death may be a promising therapeutic target.

Ferroptosis is a novel form of cell death precisely regulated by iron metabolism, antioxidant processes, and lipid metabolism that plays an irreplaceable role in the development of many diseases. Musculoskeletal disorders (MSKs), including osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, sarcopenia, and rhabdomyolysis, have become one of the most common causes of disability and a major burden on public health and social care systems. The mechanism of ferroptosis in MSKs has recently been elucidated. In this review, we briefly introduce the ferroptosis mechanism and illustrate the pathological roles of ferroptosis in MSKs with a focus on how ferroptosis can be exploited as a promising treatment strategy. Notably, because the toxicity of compounds that inhibit or induce ferroptosis in other organs is largely unknown, ferroptosis appears to be a double-edged sword. We point out that more research is needed in the future to verify the therapeutic effects based on ferroptosis in MSKs.

Elucidating the relationship between dyslipidemia and osteoporosis: A multicenter, prospective cohort study protocol.

Background: A previous study has shown similar factors in dyslipidemias (DL) and osteoporosis (OP). However, no cohort study has been reported on the association between DL and OP in the postmenopausal population in China. This study aims to provide epidemiological and pathophysiological evidence regarding the association between DL and bone mass and fracture risk. Methods: This is a multicenter, prospective cohort study that will have approximately 1,100 representative participants enrolled from multiple hospitals or communities in China. They will be divided into two groups according to whether or not they are exposed to dyslipidemia and will be epidemiologically investigated. Each participant will be visited continuously once every year with a minimum follow-up of 3 years to track incidences of OP. Meanwhile, free bone density screening, questionnaires, and blood sample collection will also be completed during this period. Conclusion: The current study is likely to provide greater insight into the relationship between lipid metabolism and bone metabolism in postmenopausal women. Furthermore, the research result maybe fed into public health strategies with regard to metabolic disease prevention.

Bu-Gu-Sheng-Sui decoction promotes osteogenesis via activating the ERK/Smad signaling pathways.

Osteoporosis is a systemic metabolic skeletal disease, which becomes a common public health problem that seriously endangers people's health. Bu-Gu-Sheng-Sui decoction (BGSSD) is a safe and effective Chinese medicine formulation for the treatment of osteoporosis. Numerous studies have indicated that it played a significant role in bone anabolism. However, the underlying mechanism remains unclear. Herein, we selected senescence-accelerated mice prone 6 (SAMP6) and MC3T3-E1 cells to study the effects of BGSSD on osteogenesis and then investigated the potential mechanism of BGSSD. Our research found that BGSSD protected the bone mass in SAMP6, increased the expression of osteogenic specific factor Runx2, and improved bone trabecular structure. In vitro, BGSSD accelerated the proliferation and differentiation of MC3T3-E1 cells, which was characterized by stimulating the activity of Alkaline phosphatase (ALP) and raising the expression of Runx2. Moreover, BGSSD could effectively boost the expression levels of ERK and Smad in SAMP6 and MC3T3-E1. Therefore, we speculate that BGSSD may promote bone formation through ERK/Smad pathways. Collectively, our results highlight the importance of BGSSD as a compound in promoting osteogenic differentiation and osteogenesis, demonstrating that BGSSD may become a latent drug to prevent and treat osteoporosis.

Discovering the Potential Value of Coenzyme Q10 in Oxidative Stress: Enlightenment From a Synthesis of Clinical Evidence Based on Various Population.

Background: Oxidative stress (OS) is associated with ferroptosis. Coenzyme Q10 (CoQ10), as an adjuvant treatment, has shown to be beneficial against OS. However, the efficacy of CoQ10 as a therapeutic agent against OS has not been promptly updated and systematically investigated. Methods: A systematic literature search was performed using the Medline, EMBASE, Web of science, Cochrane Central Register of Controlled Trials, CNKI, CBM, Science direct and clinical trial. gov to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. Results: Twenty-one randomized clinical studies met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation increased the levels of antioxidant enzymes [including superoxide dismutase (SOD) (SMD = 0.63; 95% CI: 0.38 to 0.88; p < 0.001), catalase (CAT) (SMD = 0.44; 95% CI:0.16 to 0.72; p = 0.002)] significantly and the levels of malondialdehyde (MDA) (SMD = -0.68; 95% CI: 0.93 to -0.43; p < 0.001) was decreased considerably. However, significant associations were not observed between this supplement and total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity. Conclusion: CoQ10 can improve OS as indicated by statistical significance in CAT and MDA concentrations, as well as SOD activity. Future studies focusing on long-term results and specific valuation of OS parameters are required to confirm the efficacy of CoQ10 on OS. We also believe that with the further research on ferroptosis, CoQ10 will gain more attention. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021120123].

Baduanjin exercise: A potential promising therapy toward osteoporosis.

Purpose: Baduanjin (BDJ) exercise is a traditional exercise that combines breathing, body movement, meditation and awareness to help delay the onset and progression of senile degenerative musculoskeletal diseases, such as osteoporosis (OP). The aim of this meta-analysis is to evaluate the efficacy of BDJ exercise, and preliminarily infer its effective mechanism in the treatment of OP. Methods: We identified relevant randomized controlled trials (RCTs) through eight databases, and compared BDJ exercise with the control groups (including blank control and conventional treatment intervention). The main outcome measure was bone mineral density (BMD), the additional outcome measures were visual analogue scale (VAS), Berg balance scale (BBS), serum Calcium (Ca), serum Phosphorus (P), serum Alkaline phosphatase (ALP), and serum bone gla protein (BGP). Meta-analysis and trial sequence analysis (TSA) were performed using RevMan 5.4, Stata 16.0, and TSA 0.9. Results: In total, 13 RCTs involving 919 patients were included in the analysis. For postmenopausal osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine. BDJ exercise alone can influence serum Ca and ALP. BDJ exercise combined with conventional treatment can improve balance (BBS) and influence serum BGP. For senile osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve balance (BBS). BDJ exercise combined with conventional treatment can improve the BMD of hip and pain relieve (VAS). For primary osteoporosis, BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine and femoral neck. Conclusion: Baduanjin exercise may be beneficial to improve BMD, relieve pain, improve balance ability, influence serum BGP and serum ALP in patients with OP, but differences occur due to various types of OP. Due to the low quality of research on the efficacy and mechanism of BDJ exercise in the treatment of OP, high-quality evidence-based research is still needed to provide reliable supporting evidence. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022329022].

IL-6 and Leptin Are Potential Biomarkers for Osteoporotic Fracture Risk Assessment and Prediction of Postmenopausal Women with Low Bone Mass: A Follow-Up Study Using a Regional Sample Cohort.

Osteoporotic fracture, a major complication which is known as the outcome postmenopausal osteoporosis, seriously threatens the health of postmenopausal women. At present, the traditional osteoporotic fracture prediction methods are characterized by inconvenient application and time-consuming statistical results, while predictive serum biomarkers can make up for this shortcoming. Accurate and advanced risk prediction of osteoporotic fracture is meaningful to early prevention and intervention, effectively avoiding the risk of this disease and the secondary fracture in the surgical treatment. In this study, based on the BEYOND cohort, a 2-year follow-up study was conducted after subjects participated to survey if OF occurred. Independent sample t-test and Mann-Whitney U-test were used to analyze the differences of bone metabolism biomarkers between the OF and non-OF group. Cox proportional hazard model was used to screen the potential biomarkers might be used to predict OF risk. ROC curves and AUCs were used to analyze the predictive accuracy, and the Delong's test was used to compare the differences between the AUCs. 15 postmenopausal women with low bone mass and OF were found, and other 60 subjects without OF were matched with 1 : 4, age, and BMI classification as control group. The serum IL-6 (OR = 1.139, 95%CI = 1.058 - 1.226) and leptin (OR = 0.921, 95%CI = 0.848 - 1.000) were found as OF risk predictive biomarkers for postmenopausal women with low bone mass with high accuracy (IL - 6 = 0.871) (leptin = 0.813) and accuracy enhanced when they were combined (AUC = 0.898). The results of Delong's test showed that the difference of AUC between leptin and IL-6&Leptin was meaningful (P = 0.024) but meaningless between IL-6 and leptin (P = 0.436), IL-6 and IL-6&Leptin (P = 0.606). To sum up, IL-6 and leptin are the predictive biomarkers of OF for postmenopausal women with low bone mass. The IL-6 can improve the prediction accuracy of leptin (P = 0.024), but not vice versa (P = 0.606). Trial Information. Registered on the Chinese Clinical Trial Registry already. (Registration Number: ChiCTR-SOC-17013090).

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation.

Background: Glucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis caused by the protracted or a large dosage of glucocorticoids (GCs). Total flavonoids of Drynariae rhizoma (TFDR) have been widely used in treating postmenopausal osteoporosis (POP). However, their therapeutic effects and potential mechanism against GIOP have not been fully elucidated. Methods: Ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESIQ-TOF-MS) experiments were performed for qualitative analysis. We performed hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis to detect the changes in bone microstructure. The changes in biochemical parameters in the serum samples were determined by performing an enzyme-linked immunosorbent assay (ELISA). The prediction results of network pharmacology were verified via quantitative real-time polymerase chain reaction (qRT-PCR) to elucidate the potential mechanism of TFDR against GIOP. Results: A total of 191 ingredients were identified in vitro and 48 ingredients in vivo. In the in-vivo experiment, the levels of the serum total cholesterol (TC), the serum triglyceride (TG), Leptin (LEP), osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRACP) and type-I collagen carboxy-terminal peptide (CTX-1) in the TFDR group significantly changed compared with those in the GIOP group. Moreover, the TFDR group showed an improvement in bone mineral density and bone microstructure. Based on the results of network pharmacology analysis, 67 core targets were selected to construct the network and perform PPI analysis as well as biological enrichment analysis. Five of the targets with high "degree value" had differential gene expression between groups using qRT-PCR. Conclusion: TFDR, which may play a crucial role between adipose metabolism and bone metabolism, may be a novel remedy for the prevention and clinical treatment of GIOP.