Investigating the association between serum ADAM/ADAMTS levels and bone mineral density by mendelian randomization study.

PURPOSE: A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) have been reported potentially involved in bone metabolism and related to bone mineral density. This Mendelian Randomization (MR) analysis was performed to determine whether there are causal associations of serum ADAM/ADAMTS with BMD in rid of confounders. METHODS: The genome-wide summary statistics of four site-specific BMD measurements were obtained from studies in individuals of European ancestry, including forearm (n = 8,143), femoral neck (n = 32,735), lumbar spine (n = 28,498) and heel (n = 426,824). The genetic instrumental variables for circulating levels of ADAM12, ADAM19, ADAM23, ADAMTS5 and ADAMTS6 were retrieved from the latest genome-wide association study of European ancestry (n = 5336 ~ 5367). The estimated causal effect was given by the Wald ratio for each variant, the inverse-variance weighted model was used as the primary approach to combine estimates from multiple instruments, and sensitivity analyses were conducted to assess the robustness of MR results. The Bonferroni-corrected significance was set at P < 0.0025 to account for multiple testing, and a lenient threshold P < 0.05 was considered to suggest a causal relationship. RESULTS: The causal effects of genetically predicted serum ADAM/ADAMTS levels on BMD measurements at forearm, femoral neck and lumbar spine were not statistically supported by MR analyses. Although causal effect of ADAMTS5 on heel BMD given by the primary MR analysis (ß = -0.006, -0.010 to 0.002, P = 0.004) failed to reach Bonferroni-corrected significance, additional MR approaches and sensitivity analyses indicated a robust causal relationship. CONCLUSION: Our study provided suggestive evidence for the causal effect of higher serum levels of ADAMTS5 on decreased heel BMD, while there was no supportive evidence for the associations of ADAM12, ADAM19, ADAM23, and ADAMTS6 with BMD at forearm, femoral neck and lumbar spine in Europeans.

Pre-Surgery Hip-Knee-Ankle Angle and Weightbearing Line Percentage Are Nearly Perfectly Correlated to the Miniaci Angle When Planning Open Wedge High Tibial Osteotomies.

PURPOSE: To investigate the conversion formulas between the Miniaci angle, presurgery parameters, and changes in presurgery parameters in open-wedge high tibial osteotomy (OWHTO), including hip-knee-ankle (HKA) angle, weightbearing line (WBL) percentage, mechanical medial proximal tibial angle (mMPTA), ΔHKA angle, ΔWBL percentage, ΔmMPTA, and other parameters. METHODS: From January 2012 to December 2019, 247 lower limbs of 144 patients with medial unicompartmental knee osteoarthritis combined with proximal tibia vara were enrolled. Inclusion criteria were adults, medial unicompartmental knee osteoarthritis, Kellgren-Lawrence classification grade ≤ III, mMPTA ≤ 85°, normal mechanical lateral distal femoral angle (85°-90°), and patella facing anterior in the bipedal standing position. Exclusion criteria were history of fracture, trauma, or orthopaedic surgery; developmental dysplasia of the hip or femoral head necrosis; femoral bowing deformity; deformity of the tibial shaft; and leg length discrepancy. Using standing whole-leg radiographs, an OWHTO simulation was performed to determine the Miniaci angle by delivering the WBL to the Fujisawa point. The relationship of the Miniaci angle, the presurgery parameters, and the changes in presurgery parameters were analyzed by Spearman's correlation and linear regression analyses. The relationship between the postsurgery HKA angle and presurgery parameters was analyzed by multiple linear regression model. RESULTS: The Miniaci angle showed a near-perfect correlation with the presurgery HKA angle (y = -1.05x + 192.10, r2 = 0.99), presurgery WBL percentage (y = -0.25x + 15.14, r2 = 0.97), ΔHKA angle (y = 1.04x - 0.03, r2 = 1.00), ΔWBL percentage (y = 0.25x - 0.52, r2 = 0.97), and ΔmMPTA (y = 1.04x - 0.03, r2 = 1.00). The ΔHKA angle showed nearly perfect correlation with the ΔmMPTA (y = 1.00x, r2 = 1.00), and ΔWBL percentage (y = 0.24x - 0.47, r2 = 0.97). CONCLUSIONS: The presurgery HKA angle, presurgery WBL percentage, ΔHKA angle, ΔWBL, and ΔmMPTA percentage are nearly perfectly correlated to the Miniaci angle, whereas the ΔmMPTA and ΔWBL percentage are nearly perfectly correlated to the ΔHKA angle. With the conversion formulas determined in the current study, surgeons can calculate the Miniaci angle based on the presurgery parameters without the assistance of digital software for complex surgical simulation. The Miniaci angle is closely related to the gap of the medial opening wedge. Based on the Miniaci angle and the depth of the osteotomy, surgeons can calculate the gap required before surgery using trigonometric functions and then simply measure the gap during surgery.

Lateral tibial intercondylar eminence is a reliable reference for alignment correction in high tibial osteotomy.

PURPOSE: The purpose of the study is to determine whether the lateral tibial intercondylar eminence (LTIE) is a reliable reference for alignment correction in high tibial osteotomy (HTO). METHODS: A total of 1954 consecutive standing whole-leg radiography (WLR) examinations of 1373 adult patients with knee osteoarthritis between 2012 and 2019 were reviewed retrospectively; 145 patients were included, 53 males and 92 females, with a mean age of 63.3 years. Virtual simulation of HTO was performed to measure weight-bearing line (WBL) percentages and hip-knee-ankle (HKA) angles when the WBL passed through the Fujisawa, top, bottom, upper 1/3, and middle points of the lateral slope of the LTIE, and the positional relationship between the Fujisawa point and the lateral slope of the LTIE was determined. RESULTS: When the WBL passed through the top, bottom, upper 1/3, and middle points of the lateral slope of the LTIE, the mean WBL percentages were 57.7% ± 2.1%, 74.6% ± 3.3%, 63.4% ± 2.1%, and 66.2% ± 2.3%, respectively, and the mean HKA angles were 182.1° ± 0.5°, 185.9° ± 0.8°, 183.3° ± 0.5°, and 184.0° ± 0.5°, respectively. When the WBL passed through the Fujisawa point, it was passing through 28.6% ± 12.7% of the width of the lateral slope (the top and bottom points were defined as 0% and 100%, respectively). When the WBL passed through the middle and upper 1/3 points of the lateral slope of the LTIE, the majority of cases (96.1%-100%) were within the limits of acceptability, as defined by the widely accepted standard of a postoperative HKA angle ranging from 183° to 186°. CONCLUSION: The upper 1/3 and middle points of the lateral slope of the LTIE are reliable references for guiding the alignment correction in HTO. In clinical application, if 62%-66% of the postoperative WBL percentage is the acceptable target range, the upper 1/3 point of the lateral slope of the LTIE may be a better alternative than the midpoint. If the postoperative HKA angle between 183° and 186° is acceptable, the midpoint of the lateral slope of the LTIE may be better than the upper 1/3 point. These findings are crucial for the accuracy of the traditional intraoperative alignment assessment techniques. LEVEL OF EVIDENCE: IV.

Percutaneous endoscopic debridement with percutaneous pedicle screw fixation for lumbar pyogenic spondylodiscitis: a preliminary study.

PURPOSE: To access the feasibility and efficacy of percutaneous endoscopic debridement (PED) combined with percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar pyogenic spondylodiscitis. METHODS: Forty-five patients diagnosed as pyogenic spondylodiscitis underwent PPSF followed by PED. A drainage catheter was left in place for negative pressure drainage. Adequate systematic antibiotics were administered empirically or based on bacterial culture results. Clinical outcomes were assessed by physical examination, regular serologic testing, visual analog scale (VAS), Oswestry Disability Index (ODI), and imaging studies. RESULTS: The mean operative time was 110.1 ± 21.2 minutes (range 80-165 minutes), with intra-operative blood loss 47.8 ± 21.0 ml (range 20-120 ml). All patients reported relief of back pain, able to sit up, and partially ambulate the next day. Causative pathogens were identified in 32 of 45 biopsy specimens, staphylococcal bacteria being the most prevalent strain. However, there were 13 patients with post-operative complications. During 6-12 months' follow-up, inflammatory markers showed infection controlled. VAS and ODI values were significantly improved. DISCUSSION: Satisfactory clinical and functional outcomes were achieved in our patients post-operatively. It is recommended that PED plus PPSF can be another alternative for spondylodiscitis. CONCLUSION: PED supplementing PPSF offers a valid option in treating spondylodiscitis, as it is minimally invasive, shortens hospital stay, and avoids prolonged bed rest with an optimistic outcome.

Comparison of outcomes of arthrodesis and reconstruction (advancement), posterior tibial tendon with excision of accessory tarsal navicular bone (Kidner procedure) in type 2 accessory navicula.

BACKGROUND: The therapeutic outcome of the local arthrodesis surgery for type 2 accessory navicula (AN) is rarely reported. This study aimed to compare the clinical outcomes between Kidner and arthrodesis procedures for type 2 AN. METHODS: Sixteen patients (20 feet) with symptomatic type 2 AN receiving surgical treatment in our hospital between November 2013 and December 2015 were retrospectively included. Ten patients (13 feet) underwent the Kidner surgery (Kidner group) and 6 patients received local arthrodesis procedure (arthrodesis group). Radiographic indices before/after surgery were compared between the two groups. Patient's satisfaction with surgery outcome was evaluated by patient self-assessment questionnaire. RESULTS: The calcaneal pitch angle was significantly increased after surgery in both groups (bothp<0.01), while the talocalcaneal coverage angle and lateral talo-first metatarsal angle were not significantly changed after surgery. There was no significant difference regarding the postoperative changes in the three radiographic indices between the two groups. In the arthrodesis group, 3 patients (4 feet) had an excellent outcome, 2 patients (2 feet) a good outcome, and 1 patient (1 foot) had a fair outcome. In the Kidner group, 6 patients (8 feet), 2 patients (3 feet), 1 patient (1 foot) and 1 patient (1 foot) had excellent, good, fair, and poor treatment outcomes, respectively. The rate of good-to-excellent outcomes was comparable between the arthrodesis group and Kidner group (83% vs. 80%, p=0.696). CONCLUSION: Our results suggested that both the Kidner surgery and arthrodesis surgery were an effective treatment for symptomatic type 2 AN.

RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll-like receptor signaling pathway.

Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll-like receptor (TLR) signaling pathway. Regulator of G-protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen-induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), MMP-9, and interleukin 1 receptor-associated kinase-4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA-mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF-α, IL-1ß, and IL-17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP-2, MMP-9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.

MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL.

BACKGROUND/AIMS: In this study, the molecular mechanisms of miR-27b and lipoprotein lipase (LPL) that regulate human adipose-derived mesenchymal stem cells (hASCs) adipogenic differentiation were detected. METHODS: Microarray analysis was applied to screen for differentially expressed miRNAs and mRNA during hASCs adipocyte differentiation induction. MiR-27b and LPL were found to have abnormal expression. Then, a dual luciferase reporter assay was employed to validate the targeting relationship between miR-27b and LPL. We also utilized qRT-PCR, western blot, cellular immunofluorescence and an oil red O staining assay to analyze the regulation of miR-27b and LPL during adipogenic differentiation. RESULTS: The microarray analysis demonstrated that, during adipogenic differentiation, miR-27b was down-regulated, while LPL was up-regulated but tended to become stable 14 days after induction. A dual luciferase reporter assay confirmed the negative targeting regulatory relationship between miR-27b and LPL. After overexpressing and silencing miR-27b, LPL was found to be reversely regulated by miR-27b according to qRT-PCR and western blot. The fat-formation-related biomarkers CCAAT-enhancer binding protein α (c/EBPα) and peroxisome proliferator-activated receptors γ (PPARγ) had decreasing levels after over-expressing miR-27b or knockdown of LPL followed by adipogenic differentiation. Meanwhile, the oil red O staining assay revealed that the accumulation of lipid droplets decreased. There was no change in the expression of c/EBPα, PPARγ, or lipid droplet accumulation when overexpressing miR-27b and LPL. CONCLUSION: During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs.

Trajectories and the influencing factors of behavior problems in preschool children: a longitudinal study in Guangzhou, China.

BACKGROUND: Since child mental health problem was a global health issue, many researchers in western countries has focused on the trajectory of it to provide evidence for prevention programs. We designed this study to determine the trajectories of children's behavior problems, and to explore the effect of parent predictors on children's behavior problems in Guangzhou, China. METHODS: Children (N = 1480) for this longitudinal, population-based survey, were recruited from eight regular kindergartens (October, 2010) across four districts in Guangzhou. Repeated measurement design analysis was used to compare the variation in behavioral problems by gender, only child status, and temperament. Logistic regression was applied to analyze the effect of parents' risks (maternal depression, parenting style) on the change in child problem behaviors. RESULTS: The scores of behavior problems (externalizing, emotional, social communication problems) were stable during the entire preschool period by gender and child number. Children with difficult temperament exhibited more problem behaviors than children with easy temperament in the early years, and the misbehaviors declined significantly over time. Moreover, maternal depression and the increase in excessive interference/over protective or punishing parenting strategies resulted in an increase in child behavior problems. CONCLUSION: There was no difference between the only-child status and child with siblings in the trajectory of problem behaviors. Parent factors were significant predictions of trajectory of child behavior problem during preschool age.

Comparison of smith-petersen osteotomy, pedicular subtraction osteotomy, and poly-segmental wedge osteotomy in treating rigid thoracolumbar kyphotic deformity in ankylosing spondylitis a systematic review and meta-analysis.

BACKGROUND: This study aimed to compare Smith-Petersen osteotomy (SPO), poly-segmental wedge osteotomy (PWO) and pedicular subtraction osteotomy (PSO) in patients with rigid thoracolumbar kyphosis primarily caused by ankylosing spondylitis. The efficiency, efficacy and safety of these three osteotomies have not been compared systematically, and no illness-oriented surgical type selection strategy for the treatment of ankylosing spondylitis related to non-angular kyphosis has been reported. METHODS: The inclusion and exclusion criteria were defined, and 19 electronic databases were searched for eligible studies without language limitations. For the included studies, data extraction, bias analysis, heterogeneity analysis and quantitative analysis were performed to analyze the correction of kyphosiskyphosis and the incidence of complications. RESULTS: Nine comparative studies that met the standards were included with a total of 539 patients that underwent SPO (n = 120), PWO (n = 119), or PSO (n = 300). The correction of kyphosis by PSO was 8.74° [95% CI: 0.7-16.78] greater than SPO. The correction of kyphosis by PWO was 13.88° [95 % CI: 9.25-18.51] greater than SPO. For local biomechanical complications, the pooled risk ratio of PWO to PSO was 1.97 [95 % CI: 1.03-3.77]. For blood loss, PSO was 806.42 ml [95% CI: 591.72-1021.12] greater than SPO and 566.76 ml [95 % CI: 129.80-1003.72] greater than PWO. CONCLUSIONS: To treat rigid thoracolumbar kyphosis, PSO showed higher efficiency and efficacy than SPO, and PWO had a higher efficacy than SPO. The risk of local biomechanical complications was greater in PWO than PSO. Bleeding was more severe in PSO than in SPO or PWO. The incidence of neural complications and systemic complications was similar.

Postoperative quality of life in patients with ankylosing spondylitis and thoracolumbar kyphosis: risk factors and personalized sagittal reconstruction strategy.

OBJECTIVE: The aim of this study was to investigate the factors affecting postoperative quality of life in patients with ankylosing spondylitis (AS) and thoracolumbar kyphosis (TLK), and establish a personalized sagittal reconstruction strategy. METHODS: Patients with AS and TLK who underwent pedicle subtraction osteotomy (PSO) from February 2009 to May 2019 were retrospectively included. Quality of life and spinal sagittal radiographic parameters were collected before surgery and at the last follow-up. Patients were divided into two groups based on the attainment of minimal clinically important difference (MCID) on the Bath Ankylosing Spondylitis Functional Index and Oswestry Disability Index. Comparisons of radiographic parameters and clinical outcomes were conducted between and within groups. Regression analysis was used to identify the risk factors within the missing MCID cohort. Sagittal reconstruction equations were established using the pelvic incidence (PI) and thoracic inlet angle (TIA) in the reached MCID cohort. RESULTS: The study comprised 82 participants. Significant improvements were observed in most radiographic parameters and all quality-of-life indicators during the final follow-up compared with the preoperative measures (p < 0.05). Factors including cervical lordosis (CL) ≥ 18° (OR 9.75, 95% CI 2.26-58.01, p = 0.005), chin-brow vertical angle (CBVA) ≥ 25° (OR 14.7, 95% CI 3.29-91.21, p = 0.001), and pelvic tilt (PT) ≥ 33° (OR 21.77, 95% CI 5.92-103.44, p < 0.001) independently correlated with a failure to attain MCID (p < 0.05). Sagittal realignment targets were constructed as follows: sacral slope (SS) = 0.84 PI - 17.4° (R2 = 0.81, p < 0.001), thoracic kyphosis (TK) = 0.51 PI + 10.8° (R2 = 0.46, p = 0.002), neck tilt (NT) = 0.52 TIA - 5.8° (R2 = 0.49, p < 0.001), and T1 slope (T1S) = 0.48 TIA + 5.8° (R2 = 0.45, p = 0.002). CONCLUSIONS: PSO proved efficacious in treating AS complicated by TLK, yielding favorable outcomes. CBVA ≥ 25°, CL ≥ 18°, and PT ≥ 33° were the primary factors affecting postoperative quality of life in patients with AS. The personalized sagittal reconstruction strategy in this study focused on the subjective sensations and daily needs of patients with AS, which were delineated by the equations SS = 0.84 PI - 17.4°, TK = 0.51 PI + 10.8°, NT = 0.52 TIA - 5.8°, and T1S = 0.48 TIA + 5.8°.

Multilevel Pedicle Subtraction Osteotomy for Correction of Thoracolumbar Kyphosis in Ankylosing Spondylitis: Clinical Effect and Biomechanical Evaluation.

OBJECTIVE: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. METHODS: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. RESULTS: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. CONCLUSION: Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Application of vertebral body compression osteotomy in pedicle subtraction osteotomy on ankylosing spondylitis kyphosis: Finite element analysis and retrospective study.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, with pathological characteristics of bone erosion, inflammation of attachment point, and bone ankylosis. Due to the ossified intervertebral disc and ligament, pedicle subtraction osteotomy (PSO) is one of the mainstream surgeries of AS-related thoracolumbar kyphosis, but the large amount of blood loss and high risk of instrumental instability limit its clinical application. The purpose of our study is to propose a new transpedicular vertebral body compression osteotomy (VBCO) in PSO to reduce blood loss and improve stability. Methods: A retrospective analysis was performed on patients with AS-related thoracolumbar kyphosis who underwent one-level PSO in our hospital from February 2009 to May 2019. A total of 31 patients were included in this study; 6 received VBCO and 25 received eggshell vertebral body osteotomy. We collected demographic data containing gender and age at diagnosis. Surgical data contained operation time, estimated blood loss (EBL), and complications. Radiographic data contained pre-operative and follow-up sagittal parameters including chin brow-vertical angle (CBVA), global kyphosis (GK), thoracic kyphosis (TK), and lumbar lordosis (LL). A typical case with L2-PSO was used to establish a finite element model. The mechanical characteristics of the internal fixation device, vertebral body, and osteotomy plane of the two osteotomy models were analyzed under different working conditions. Results: The VBCO could provide comparable restoring of CBVA, GK, TK, and LL in the eggshell osteotomy procedure (all p > 0.05). The VBCO significantly reduced EBL compared to those with eggshell osteotomy [800.0 ml (500.0-1,439.5 ml) vs. 1,455.5 ml (1,410.5-1,497.8 ml), p = 0.033]. Compared with the eggshell osteotomy, VBCO showed better mechanical property. For the intra-pedicular screw fixation, the VBCO group had a more average distributed and lower stress condition on both nails and connecting rod. VBCO had a flattened osteotomy plane than the pitted osteotomy plane of the eggshell group, showing a lower and more average distributed maximum stress and displacement of osteotomy plane. Conclusion: In our study, we introduced VBCO as an improved method in PSO, with advantages in reducing blood loss and providing greater stability. Further investigation should focus on clinical research and biomechanical analysis for the application of VBCO.

Da Vinci robot-assisted laparoscopic retroperitoneal debridement for lumbar septic spondylodiscitis: A two-case report.

The anterior approach is one of the widely used surgical treatments for lumbar spondylodiscitis, but it has the disadvantages of large trauma and a high incidence of complications. Our experiences suggested that the laparoscopic retroperitoneal approach could be effective to overcome those disadvantages of the anterior approach. Herein, we report two cases of successfully treated lumbar pyogenic spondylodiscitis using a robot-assisted laparoscopic retroperitoneal approach. The technique utilizes a robot that allows a laparoscopic retroperitoneal approach while offering excellent high-definition images of three-dimensional vision. After the operation, both patients achieved good formation and fusion of the vertebrae. Preliminary evidence suggests that the robot-assisted laparoscopic retroperitoneal approach may be feasible for the treatment of lumbar spondylodiscitis.

Thoracolumbar kyphosis in postmenopausal osteoporosis patients without vertebral compression fractures.

Background: To investigate whether thoracolumbar kyphosis (TLK) of the spine is related to the reduction of bone mineral density (BMD) in postmenopausal osteoporosis women, and whether BMD of postmenopausal osteoporosis women can predict the occurrence of TLK. Methods: This retrospective cohort study included 224 postmenopausal female patients hospitalized for osteoporosis from December 2017 to December 2020, and the control group included 270 postmenopausal female patients hospitalized for thoracolumbar degenerative diseases. The age, body mass index (BMI), visual analogue scale (VAS), and BMD of the lumbar spine [BMD(L)] and femoral neck [BMD(F)] of all patients during admission were recorded. We measured and recorded the Cobb angle of thoracolumbar and the height of the thoracolumbar intervertebral space in the spinal X-ray lateral radiograph. The Pearson and Spearman correlation coefficients were used to calculate the correlation between each parameter in the group. The Chi-square test was used for categorical variables, the independent-sample t-test was used for normally distributed continuous variables, and two-sample non-parametric tests were used for non-normally distributed variables. Binary logistic regression analysis and receiver operating characteristic (ROC) curves were applied to determine independent risk factors and cut-off values, respectively. Results: There were significant differences in the BMD(L), BMD(F), thoracolumbar junction Cobb angle, lumbar spine Cobb angle, T11/12-L1/2 height difference of the posterior and anterior edge of intervertebral space (HDPAIS), single vertebra Cobb angle (SVC), procollagen type 1 N-terminal propeptide (PINP) and 25-hydroxyvitamin D [25-(OH)D] between the study and control groups. Through binary logistic regression analysis, we found that BMD(L), PINP, bone alkaline phosphatase, and 25-(OH)D were independent risk factors for future TLK in postmenopausal women. According to the ROC curve, the prediction accuracy of BMD(L) was the highest. By calculating the critical value, we found that when the BMD(L) T-score <-1.65, postmenopausal women were more likely to develop TLK. Conclusions: In postmenopausal osteoporosis patients, TLK will occur even if there is no compression fracture, and when the BMD(L) T-score <-1.65, postmenopausal women are more likely to develop TLK in the future.

Prognostic Nomogram of Osteocarcinoma after Surgical Treatment.

Purpose: This study aimed to establish a valid prognostic nomogram for osteocarcinoma after surgical management. Methods: Based on the SEER database, we retrieved the clinical variables of patients confirmed to have osteocarcinoma between 1975 and 2016. Then, we performed univariate and multivariate analyses and constructed a nomogram of overall survival. Results: Multivariate analysis of the primary cohort revealed that the independent factors for survival were age, grade, pathologic stage, T stage, and surgery performed. All these factors were showed by the nomogram. The correction curve of survival probability showed that the prediction results of nomogram well agreed with the actual observation results. The C index of the nomogram used to predict survival was 0.82; the AUC of 1-year, 3-year, and 5-year survival rates in the training cohort were 0.9, 0.819, and 0.80631, respectively, indicating that the model was accurate and reliable; whether the operation was performed or not; T stage; grade; and age were the main factors affecting the survival of patients. The AUC of the validation cohort for 1 year, 3 years, and 5 years were 0.8, 0.831, and 0.80023, respectively. Conclusion: The proposed nomogram can more accurately predict the prognosis of patients with osteocarcinoma after surgical management. This could be a potential method that services clinical work.

Retraction Notice to: Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1.

[This retracts the article DOI: 10.1016/j.omtn.2019.11.015.].

Study on the clinical efficacy of bone-filled mesh vertebroplasty combined with posterior screw and rod internal fixation in the treatment of thoracolumbar metastases: a retrospective cohort study.

BACKGROUND: Thoracolumbar metastases is a difficult disease to deal with in spinal surgery. The aim of this study is to investigate the clinical efficacy of bone-filled mesh vertebroplasty combined with posterior spinal internal fixation in the treatment of thoracolumbar metastases. METHODS: The clinical data of 68 patients with thoracolumbar vertebral metastases from January 2018 to April 2020 were retrospectively analyzed. A total of 37 cases underwent bone filling mesh pocket vertebroplasty combined with posterior spinal internal fixation as the observation group, and 31 cases underwent routine vertebroplasty combined with posterior spinal internal fixation as the control group. The visual analogue scale (VAS) scores, Oswestry disability index (ODI) scores, Karnofsky performance status (KPS) scores, and the heights of the anterior margin and middle of the diseased vertebra were compared between the 2 groups before and 1 week, 3 months, 6 months, and 1 year after surgery. RESULTS: All cases successfully completed the operation, and there was no pulmonary embolism, paraplegia, or perioperative death in follow-up reported. Intraoperative bone cement leakage occurred in 4 cases with a total of 6 vertebrae in the observation group (leakage rate: 14.29%), and in 8 cases with a total of 11 vertebrae in control group (leakage rate: 31.43%). The differences in VAS scores, ODI scores, KPS scores, and the heights of the anterior margin and middle of the diseased vertebra between preoperative and postoperative periods at 1 week, 3 months, 6 months, and 1 year in both groups were statistically significant (P<0.05), while the differences between the 2 groups were not statistically significant (P<0.05). CONCLUSIONS: The application of bone-filled mesh vertebroplasty combined with posterior internal pedicle screws fixation for the treatment of thoracolumbar metastases can not only reduce the injury of the operation, but also achieve the purpose of relieving pain, controlling local tumor growth to a certain extent, restoring neural function, and rebuilding the stability of the spine, which has important clinical value.

Circulating Monocytes Act as a Common Trigger for the Calcification Paradox of Osteoporosis and Carotid Atherosclerosis via TGFB1-SP1 and TNFSF10-NFKB1 Axis.

Background: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the "calcification paradox". Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD14+ monocytes contribute to the pathophysiology of coexisting postmenopausal osteoporosis and carotid atherosclerosis. Methods: We comprehensively analyzed osteoporosis data from the mRNA array dataset GSE56814 and the scRNA-seq dataset GSM4423510. Carotid atherosclerosis data were obtained from the GSE23746 mRNA dataset and GSM4705591 scRNA-seq dataset. First, osteoblast and vascular SMC lineages were annotated based on their functional expression using gene set enrichment analysis and AUCell scoring. Next, pseudotime analysis was applied to draw their differentiated trajectory and identify the key gene expression changes in crossroads. Then, ligand-receptor interactions between CD14+ monocytes and osteoblast and vascular smooth muscle cell (SMC) lineages were annotated with iTALK. Finally, we selected calcification paradox-related expression in circulating monocytes with LASSO analysis. Results: First, we found a large proportion of delayed premature osteoblasts in osteoporosis and osteogenic SMCs in atherosclerosis. Second, CD14+ monocytes interacted with the intermediate cells of the premature osteoblast and osteogenic SMC lineage by delivering TGFB1 and TNFSF10. This interaction served as a trigger activating the transcription factors (TF) SP1 and NFKB1 to upregulate the inflammatory response and cell senescence and led to a retarded premature state in the osteoblast lineage and osteogenic transition in the SMC lineage. Then, 76.49% of common monocyte markers were upregulated in the circulating monocytes between the two diseases, which were related to chemotaxis and inflammatory responses. Finally, we identified 7 calcification paradox-related genes on circulating monocytes, which were upregulated in aging cells and downregulated in DNA repair cells, indicating that the aging monocytes contributed to the development of the two diseases. Conclusions: Our work provides a perspective for understanding the triggering roles of CD14+ monocytes in the development of the calcification paradox in osteoporosis- and atherosclerosis-related cells based on combined scRNA and mRNA data. This study provided us with an elucidation of the mechanisms underlying the calcification paradox and could help in developing preventive and therapeutic strategies.

Development of a Chemoresistant Risk Scoring Model for Prechemotherapy Osteosarcoma Using Single-Cell Sequencing.

Background: Chemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing. Methods: We comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand-receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration. Results: Using bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups (AUCtrain = 0.82; AUCvalid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment (AUCvalid-scRNA = 0.84; AUCvalid-bulk DEGs = 0.54). Conclusions: Our work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma.