Bingqiang Wang

Validation of an osteoporosis self-assessment tool to identify primary osteoporosis and new osteoporotic vertebral fractures in postmenopausal Chinese women in Beijing.

BackgroundThis study aimed to validate the effectiveness of the Osteoporosis Self-assessment Tool for Asians (OSTA) in identifying postmenopausal women at increased risk of primary osteoporosis and painful new osteoporotic vertebral fractures in a large selected Han Chinese population in Beijing.MethodsWe assessed the performance of the OSTA in 1201 women. Subjects with an OSTA index > -1 were classified as the low risk group, and those with an index ≤ -1 were classified as the increased risk group. Osteoporosis is defined by a T-score ≤ 2.5 standard deviations according to the WHO criteria. All painful, new vertebral fractures were identified by X-ray and MRI scans with correlating clinical signs and symptoms. We determined the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve for correctly selecting women with osteoporosis and painful new vertebral fractures.ResultsOf the study subjects, 29.3% had osteoporosis, and the prevalence of osteoporosis increased progressively with age. The areas under the ROC curves of the OSTA index (cutoff = -1) to identify osteoporosis in the femoral neck, total hip, and lumbar spine were 0.824, 0.824, and 0.776, respectively. The sensitivity and specificity of the OSTA index (cutoff = -1) to identify osteoporosis in healthy women were 66% and 76%, respectively. With regard to painful new vertebral fractures, the area under the ROC curve relating the OSTA index (cutoff = -1) to new vertebral fractures was 0.812.ConclusionsThe OSTA may be a simple and effective tool for identifying the risk of osteoporosis and new painful osteoporotic vertebral fractures in Han Chinese women.

Epidural injections with or without steroids in managing chronic low back pain secondary to lumbar spinal stenosis: a meta-analysis of 13 randomized controlled trials.

Background Epidural injections of anesthetic with or without steroids are widely used for treating lumbar spinal stenosis, a common cause of chronic low back pain, but there is a lack of rigorous data comparing the effectiveness of epidural injections of anesthetic with and without steroids. This meta-analysis presents a current, comprehensive picture of how epidural injections of anesthetic with steroids compare with those using local anesthetic alone. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched from their inception through February 5, 2015. Weight mean difference, risk ratio, and 95% confidence intervals were calculated. A random effects model or fixed effects model was used to pool the estimates, according to the heterogeneity between the included studies. Results We included 13 randomized controlled trials, involving 1,465 patients. Significant pain relief (≥50%) was demonstrated in 53.7% of patients administered with epidural injections of anesthetic with steroids (group 1) and in 56.4% of those administered with local anesthetic alone (group 2). Patients showed a reduction in numeric rating scale pain score of 3.7 and 3.6 in the two groups, respectively. Significant functional improvement was achieved in 65.2% of patients in group 1 and 63.1% of patients in group 2, with Oswestry Disability Index reductions of 13.8 and 14.5 points, respectively. The overall number of injections per year was 3.2±1.3 and 3.4±1.2 with average total relief per year of 29.3±19.7 and 33.8±19.3 weeks, respectively. The opioid intakes decreased from baseline by 12.4 and 7.8 mg, respectively. Among the outcomes listed, only total relief time differed significantly between the two groups. Conclusion Both epidural injections with steroids or with local anesthetic alone provide significant pain relief and functional improvement in managing chronic low back pain secondary to lumbar spinal stenosis, and the inclusion of steroids confers no advantage compared to local anesthetic alone.

Validation of three tools for identifying painful new osteoporotic vertebral fractures in older Chinese men: bone mineral density, Osteoporosis Self-Assessment Tool for Asians, and fracture risk assessment tool

Objective This cross-sectional study compared three tools for predicting painful new osteoporotic vertebral fractures (PNOVFs) in older Chinese men: bone mineral density (BMD), the Osteoporosis Self-Assessment Tool for Asians (OSTA), and the World Health Organization fracture risk assessment tool (FRAX) (without BMD). Methods Men aged ≥50 years were apportioned to a group for men with fractures who had undergone percutaneous vertebroplasty (n=111), or a control group of healthy men (n=385). Fractures were verified on X-ray and magnetic resonance imaging. BMD T-scores were determined by dual energy X-ray absorptiometry. Diagnosis of osteoporosis was determined by a BMD T-score of ≤2.5 standard deviations below the average for a young adult at peak bone density at the femoral neck, total hip, or L1–L4. Demographic and clinical risk factor data were self-reported through a questionnaire. BMD, OSTA, and FRAX scores were assessed for identifying PNOVFs via receiver-operating characteristic (ROC) curves. Optimal cutoff points, sensitivity, specificity, and areas under the ROC curves (AUCs) were determined. Results Between the men with fractures and the control group, there were significant differences in BMD T-scores (at femoral neck, total hip, and L1–L4), and OSTA and FRAX scores. In those with fractures, only 53.15% satisfied the criteria for osteoporosis. Compared to BMD or OSTA, the FRAX score had the best predictive value for PNOVFs: the AUC of the FRAX score (cutoff =2.9%) was 0.738, and the sensitivity and specificity were 82% and 62%, respectively. Conclusion FRAX may be a valuable tool for identifying PNOVFs in older Chinese men.

Identification of upstream regulators for synovial expression signature genes in osteoarthritis

OBJECTIVES The detection of transcription factors (TFs) for OA signature genes provides better clues to the underlying regulatory mechanisms and therapeutic applications. METHODS We searched GEO database for synovial expression profiling from different OA microarray studies to perform a systematic analysis. Functional annotation of DEGs was conducted, including gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Based on motif databases and the results from integrated analysis of current gene expression data, a global transcriptional regulatory network was constructed, and the upstream TFs were identified for OA signature genes. RESULTS Six GEO datasets were obtained. Totally, 805 genes across the studies were consistently differentially expressed in OA (469 up-regulated and 336 down-regulated genes) with FDR≤0.01. Supporting an involvement of ECM in the development of OA, we showed that ECM-receptor interaction was the most significant pathway in our KEGG analysis (P=5.92E-12). Sixty-one differentially expressed TFs were identified with FDR≤0.05. The constructed OA-specific regulatory networks consisted of 648 TF-target interactions between 51 TFs and 429 DEGs in the context of OA. The top 10 TFs covering the most downstream DEGs were identified as crucial TFs involved in the development of OA, including ARID3A, NFIC, ZNF354C, NR4A2, BRCA1, EHF, FOXL1, FOXC1, EGR1, and HOXA5. CONCLUSION This integrated analysis has identified the OA signature, providing clues to pathogenesis of OA at the molecular level, which may be also used as diagnostic markers for OA. Some crucial upstream regulators, such as NR4A2, EHF, and EGR1 may be considered as potential new therapeutic targets for OA.

Long-term outcomes and prognostic analysis of modified open-door laminoplasty with lateral mass screw fusion in treatment of cervical spondylotic myelopathy

Objectives The purpose of the present study was to explore and analyze the long-term outcomes and factors that affect the prognosis of expansive open-door laminoplasty with lateral mass screw fusion in treatment of cervical spondylotic myelopathy (CSM). Methods We retrospectively reviewed 49 patients with multilevel CSM who had undergone expansive open-door laminoplasty with lateral mass screws fixation and fusion in our hospital between February 2008 and February 2012. The average follow-up period was 4.6 years. The clinical data of patients, including age, sex, operation records, pre- and postoperation Japanese Orthopedic Association (JOA) scores, cervical spine canal stenosis, and cervical curvature, were collected. Increased signal intensity (ISI) on T2-weighted magnetic resonance imaging and ossification of the posterior longitudinal ligament were also observed. Paired t-test was used to analyze the treatment effectiveness and recovery of neuronal function. The prognostic factors were analyzed with multivariable linear regression model. Results Forty-nine patients with CSM with a mean age of 59.44 years were enrolled in this study. The average of preoperative JOA score was 9.14±2.25, and postoperative JOA score was 15.31±1.73. There was significant difference between the pre- and postoperative JOA scores. The clinical improvement rate was 80.27%. On follow-up, five patients had complaints of neck and shoulder pain, but no evidence of C5 nerve palsy was found. Developmental cervical spine canal stenosis was present in all patients before surgery. Before surgery, ISI was observed in eight patients, while ossification of the posterior longitudinal ligament was found in 12 patients. The average of preoperative cervical curvature was 21.27°±8.37° and postoperative cervical curvature was 20.09°±1.29°, and there was no significant difference between the pre- and postoperative cervical curvatures. Multivariable linear regression analysis results showed that the postoperation JOA scores were significantly affected by age, preoperative JOA scores, and preoperative ISI. Except one case of epidural hematoma, there were no complications associated with the surgery. Conclusion Treatment of CSM with posterior open-door laminoplasty with lateral mass screw fusion is effective with few complications. In addition, the normal cervical lordosis was well maintained. Age, preoperative JOA scores, and preoperative ISI were the independent factors that significantly affect disease prognosis and surgical outcomes.

BFH-OST, a new predictive screening tool for identifying osteoporosis in postmenopausal Han Chinese women.

Purpose To develop a simple new clinical screening tool to identify primary osteoporosis by dual-energy X-ray absorptiometry (DXA) in postmenopausal women and to compare its validity with the Osteoporosis Self-Assessment Tool for Asians (OSTA) in a Han Chinese population. Methods A cross-sectional study was conducted, enrolling 1,721 community-dwelling postmenopausal Han Chinese women. All the subjects completed a structured questionnaire and had their bone mineral density measured using DXA. Using logistic regression analysis, we assessed the ability of numerous potential risk factors examined in the questionnaire to identify women with osteoporosis. Based on this analysis, we build a new predictive model, the Beijing Friendship Hospital Osteoporosis Self-Assessment Tool (BFH-OST). Receiver operating characteristic curves were generated to compare the validity of the new model and OSTA in identifying postmenopausal women at increased risk of primary osteoporosis as defined according to the World Health Organization criteria. Results At screening, it was found that of the 1,721 subjects with DXA, 22.66% had osteoporosis and a further 47.36% had osteopenia. Of the items screened in the questionnaire, it was found that age, weight, height, body mass index, personal history of fracture after the age of 45 years, history of fragility fracture in either parent, current smoking, and consumption of three of more alcoholic drinks per day were all predictive of osteoporosis. However, age at menarche and menopause, years since menopause, and number of pregnancies and live births were irrelevant in this study. The logistic regression analysis and item reduction yielded a final tool (BFH-OST) based on age, body weight, height, and history of fracture after the age of 45 years. The BFH-OST index (cutoff =9.1), which performed better than OSTA, had a sensitivity of 73.6% and a specificity of 72.7% for identifying osteoporosis, with an area under the receiver operating characteristic curve of 0.797. Conclusion BFH-OST may be a powerful and cost-effective new clinical risk assessment tool for prescreening postmenopausal women at increased risk for osteoporosis by DXA, especially for Han Chinese women.

Identification of candidate genes in osteoporosis by integrated microarray analysis

Objectives In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1.

A Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Minimally Invasive Lumbar Interbody Fusion

Study Design Meta-analysis. Background Bilateral pedicle screw fixation (PS) after lumbar interbody fusion is a widely accepted method of managing various spinal diseases. Recently, unilateral PS fixation has been reported as effective as bilateral PS fixation. This meta-analysis aimed to comparatively assess the efficacy and safety of unilateral PS fixation and bilateral PS fixation in the minimally invasive (MIS) lumbar interbody fusion for one-level degenerative lumbar spine disease. Methods MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched through March 30, 2014. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion criteria and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.2. Results Six studies (5 RCTs and 1 CCT) involving 298 patients were selected. There were no significant differences between unilateral and bilateral PS fixation procedures in fusion rate, complications, visual analogue score (VAS) for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation procedures had similar length of hospital stay (MD = 0.38, 95% CI = −0.83 to 1.58; P = 0.54). In contrast, bilateral PS fixation was associated with significantly more intra-operative blood loss (P = 0.002) and significantly longer operation time (P = 0.02) as compared with unilateral PS fixation. Conclusions Unilateral PS fixation appears as effective and safe as bilateral PS fixation in MIS lumbar interbody fusion but requires less operative time and causes less blood loss, thus offering a simple alternative approach for one-level lumbar degenerative disease.

A Novel Approach for Percutaneous Vertebroplasty Based on Preoperative Computed Tomography–Based Three-Dimensional Model Design

OBJECTIVE To describe a new technique for the efficient use of preoperative planning based on preoperative computed tomography-based three-dimensional (3D) model design for percutaneous vertebroplasty (PVP) in a patient with osteoporotic vertebral compression fracture. METHODS A 76-year-old woman with acute osteoporotic vertebral compression fracture (L1 level) accepted a novel precise PVP. A 3D model of thoracolumbar vertebrae (T12-L2) based on preoperative computed tomography scanning data and a simulative PVP (via a bilateral transpedicular approach) were built in MIMICS (Materialise Interactive Medical Image Control System) software. With the help of 3 radiopaque markers located at the skin of the back and preoperative digital design by MIMICS, bilateral skin entry points, needles direction including abduction angle and head inclination angle, and needle insertion depth were established. RESULTS During surgery, only 1 shot of fluoroscopy was required to confirm the skin entry points. The operation took only about 23 minutes and total patient exposure dose was 4.5 mSv. The intraoperative radiologic results showed that the cement distribution in the L1 vertebra was good without any puncture-related complications. The patients visual analog scale score improved from 9 points preoperatively to 2 points postoperatively. The patients preoperative Oswestry Disability Index score was 80 points, which improved to 57.8 points postoperatively. CONCLUSIONS The novel precise PVP based on preoperative 3D model design allows 1) visualization of the morphology of the fractured vertebral body, 2) increased precision of puncture with decreasing incidence of puncture-related complications and reduced radiation exposure, and 3) less operation time, decreasing the learning curve of beginners with limited experience.

Potential roles of microRNAs and their target genes in human multiple myeloma

The etiology of multiple myeloma (MM) is unknown and it remains incurable. We sought to elucidate the mechanisms underlying miRNAs involvement in MM pathogenesis.