JiSheng Lin

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.

Identification of aberrantly expressed long non-coding RNAs in postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) is a common skeletal disorder in postmenopausal women. The present study aimed to identify the key long non-coding RNAs (lncRNAs) in PMOP through RNA sequencing. RNA sequencing was performed to obtain the expression profile of lncRNAs and mRNAs in blood samples of patients with PMOP and normal controls (NCs). Following the identification of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs), the DElncRNA-DEmRNA co-expression network was constructed. A search was performed for the DEGs transcribed within a 100-kb window upstream or downstream of DElncRNAs, which served as nearby DEmRNAs of DElncRNAs. Functional annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The GSE56815 dataset was used to verify the expression of selected DEmRNAs and DElncRNAs. Three blood samples from patients with PMOP and two blood samples from NCs were used for RNA sequencing. Compared with the NC group, a total of 185 DEmRNAs and 51 DElncRNAs were obtained in PMOP. A total of 3,057 co-expression DElncRNA-DEmRNA pairs and 97 DElncRNA-nearby DEmRNA pairs were obtained. Six DEmRNAs [diacylglycerol O-acyltransferase 2, potassium voltage-gated channel subfamily S member 1, peptidase inhibitor 3, secretory leukocyte peptidase inhibitor, galectin-related protein and alkaline phosphatase, liver/bone/kidney (ALPL)] were nearby co-expressed genes of four DElncRNAs, including LOC105376834, LOC101929866, LOC105374771 and LOC100506113. Three PMOP-associated DEmRNAs, including ALPL, suppressor of cytokine signaling 3 and adrenomedullin, were co-expressed with the hub DElncRNAs (LINC00963, LOC105378415, LOC105377067, HCG27, LOC101928143 and LINC01094) of the positively and negatively co-expressed DElncRNA-DEmRNA interaction network. The expression of selected DEmRNAs and DElncRNAs was consistent with the RNA-sequencing results. In conclusion, the present study identified the key DEmRNAs and DElncRNAs in PMOP, which may provide clues for understanding the mechanism and developing novel biomarkers for PMOP.

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.

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.

BFH-OSTM, a new predictive screening tool for identifying osteoporosis in elderly Han Chinese males

Purpose To develop and validate a new clinical screening tool to identify primary osteoporosis by dual-energy X-ray absorptiometry (DXA) in two elderly Han Chinese male populations. Methods A cross-sectional study was conducted, enrolling 1,870 community-dwelling and 574 hospital-checkup elderly Han Chinese males aged ≥50 years. All subjects completed a structured questionnaire and had their bone mineral density (BMD) measured using DXA. Using logistic regression analysis in the 1,870 community-dwelling males, we assessed the ability of numerous potential clinical risk factors to identify male with osteoporosis. Multiple variable regression analysis and item reduction yielded a final tool named the Beijing Friendship Hospital Osteoporosis Self-assessment Tool for Elderly Male (BFH-OSTM). Receiver operating characteristic (ROC) curve was generated to compare the validation of the BFH-OSTM and Osteoporosis Self-assessment Tool for Asians (OSTA) for identifying elderly male at increased the risk of primary osteoporosis in the 574 hospital-checkup males. Results In screening the 1,870 community-dwelling subjects with DXA, 14.2% (266/1,870) had osteoporosis, and a further 51.8% (969/1,870) had osteopenia. Of the items screened in the questionnaire, weight, height and previous history of fragility fracture were predictive of osteoporosis. A final tool (BFH-OSTM) was based on body weight and fragility fracture history only. The BFH-OSTM index (cutoff =70) had a sensitivity of 85% and specificity of 53% for identifying osteoporosis according to the WHO criteria, with an area under the ROC curve of 0.763. The predictive value of BFH-OSTM was validated in the 574 hospital-checkup population, which performed better than OSTA. Conclusion The BFH-OSTM may perform well for identifying elderly male at increased risk for osteoporosis and applying it would result in more prudent use of BMD measurement by DXA, especially for Han Chinese male.

Comparison between anterior cervical discectomy with fusion and anterior cervical corpectomy with fusion for the treatment of cervical spondylotic myelopathy: a meta-analysis.

Background Whether anterior cervical discectomy with fusion (ACDF) or anterior cervical corpectomy with fusion (ACCF) is superior in the treatment of cervical spondylotic myelopathy remains controversial. Therefore, we conducted a meta-analysis to quantitatively compare the efficacy and safety of ACDF and ACCF in the treatment of cervical spondylotic myelopathy. Methods PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, People’s Republic of China), and CNKI (China National Knowledge Infrastructure, People’s Republic of China) were systematically searched to identify all available studies comparing efficacy and safety between patients receiving ACDF and ACCF. The weighted mean difference (WMD) was pooled to compare the Japanese Orthopaedic Association scores, visual analog scale scores, hospital stay, operation time, and blood loss. The risk ratio was pooled to compare the incidence of complications and fusion rate. Pooled estimates were calculated by using a fixed-effects model or a random-effects model according to the heterogeneity among studies. Results Eighteen studies (17 observational studies and one randomized controlled trial) were included in this meta-analysis. Our results suggest that hospital stay (WMD =−1.33, 95% confidence interval [CI]: −2.29, −0.27; P=0.014), operation time (WMD =−26.9, 95% CI: −46.13, −7.67; P=0.006), blood loss (WMD =−119.36, 95% CI: −166.94, −71.77; P=0.000), and incidence of complications (risk ratio =0.51, 95% CI: 0.33, 0.80; P=0.003) in the ACDF group were significantly less than that in the ACCF group. However, other clinical outcomes, including post-Japanese Orthopaedic Association score (WMD =−0.27, 95% CI: −0.57, 0.03; P=0.075), visual analog scale score (WMD =0.03, 95% CI: −1.44, 1.50; P=0.970), and fusion rate (risk ratio =1.04, 95% CI: 0.99, 1.09; P=0.158), between the two groups were not significantly different. Conclusion Evidence from the meta-analysis of 18 studies demonstrated that surgical options of cervical spondylotic myelopathy using ACDF or ACCF seemed to have similar clinical outcomes. However, ACDF was found to be superior to ACCF in terms of hospital stay, operation time, blood loss, and incidence of complications.

Comparison of three tools for predicting primary osteoporosis in an elderly male population in Beijing: a cross-sectional study

Purpose In this cross-sectional study, three clinical tools, the Osteoporosis Self-Assessment Tool for Asians (OSTA), Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD), and body mass index (BMI), for predicting primary osteoporosis (OP) were compared and ideal thresholds for omission of screening BMD were proposed in a community-dwelling elderly Han Beijing male population. Patients and methods A total of 1,349 community-dwelling elderly Han Beijing males aged ≥50 years were enrolled in this study. All subjects completed a questionnaire and measured BMD by dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined as a T-score of −2.5 SD or lower than that of the average young adult in different diagnostic criteria (lumbar spine [L1–L4], femoral neck, total hip, worst hip, and World Health Organization [WHO]). FRAX without BMD, OSTA, and BMI were assessed for predicting OP by receiver operating characteristic (ROC) curves. Sensitivity, specificity, and areas under the ROC curves (AUCs) were determined. Ideal thresholds for omission of screening BMD were proposed. Results The prevalence of OP ranged from 1.8% to 12.8% according to different diagnostic criteria. This study showed that the BMI has highest discriminating ability. The AUC of FRAX without BMD ranged from 0.536 to 0.630, which suggested limiting predictive value for identifying OP in elderly Beijing male. The AUCs of BMI (0.801–0.880) were slightly better than OSTA (0.722–0.874) in predicting OP at all sites. The AUC of BMI to identify OP in worst hip was 0.824, yielding a sensitivity of 84.8% and a specificity of 64.4%. 40% of participants on BMD measurements saved only 0.1%–2.7% missed OP. Compared to OSTA and FRAX without BMD, the BMI got the best predictive value for OP. Conclusion BMI may be a simple and effective tool for identifying OP in the elderly male population in Beijing to omit BMD screening reasonably.