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Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated., Material and Methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese., Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10 -3 ), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10 -3 ) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10 -3 ), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI., Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Otomo, Khanshour, Koido, Takeda, Momozawa, Kubo, Kamatani, Herring, Ogura, Takahashi, Minami, Uno, Kawakami, Ito, Sato, Watanabe, Kaito, Yanagida, Taneichi, Harimaya, Taniguchi, Shigematsu, Iida, Demura, Sugawara, Fujita, Yagi, Okada, Hosogane, Kono, Nakamura, Chiba, Kotani, Sakuma, Akazawa, Suzuki, Nishida, Kakutani, Tsuji, Sudo, Iwata, Inami, Wise, Kochi, Matsumoto, Ikegawa, Watanabe and Terao.)

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Background: Surgical treatment for adolescent idiopathic scoliosis (AIS) has changed significantly with the advent of new medical devices and surgical procedures. Today, pre- and postoperative management differs widely between institutions. The purpose of this study is to establish consensus regarding the surgical management of AIS in Japan through the use of a questionnaire survey of experienced spine deformity surgeons., Methods: From February to March 2020, experienced spine deformity surgeons who perform more than 25 cases of AIS surgery annually were asked to respond to a questionnaire request regarding AIS surgical management formulated by the International Affairs Committee of the Japanese Scoliosis Society. For each of the questions, consensus was achieved upon a 70% agreement among respondents., Results: Responses were received from 25 of the 32 (78%) experienced spine deformity surgeons. The average age of the responding surgeons was 52 years with an average practice experience of 28 year. Consensus was achieved on 74 (76%) of the 97 aspects of care presented in the questionnaire and is broken down as follows: 12 of 17 items for preoperative management, all 5 items for perioperative management, 11 of 14 items for surgical technique, 9 of 15 items for implant selection, 6 of 8 items for bone grafting, 7 of 10 items for blood conservation, 5 of 7 items for postoperative management, all 17 items for postoperative evaluation, and 2 of 4 items for aftercare., Conclusions: Expert consensus was achieved on 74 aspects of the surgical management of AIS in Japan. In implant selection and aftercare, consensus was obtained in less than 70% of the aspects, revealing differences in AIS management between institutions. These findings on AIS surgery in Japan, informed by expert opinion, will conceivably help spine deformity surgeons determine appropriate surgical management of AIS., Competing Interests: Declaration of competing interest HA, TO, DK, HS, WS, HK, SS, MY, MI and DS have nothing to disclose. TK serves on the ethics review board of the Japanese Scoliosis Society., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10 -40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10 -10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10 -8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10 -4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Some surgical strategies can maintain or restore thoracic kyphosis (TK); however, next-generation surgical schemes for adolescent idiopathic scoliosis (AIS) should consider anatomical corrections. A four-dimensional correction could be actively achieved by curving the rod. Thus, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. This study aimed to compare the initial curve corrections obtained using notch-free rods and manually bent, notched rods for the anatomical reconstruction of thoracic AIS. Two consecutive series of 60 patients who underwent anatomical posterior correction for main thoracic AIS curves were prospectively followed up. After multilevel facetectomy, except for the lowest instrumented segment, either notch-free or notched rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week after surgery. Patients with notch-free rods had significantly higher postoperative TK than patients with notched rods (P < .001), but both groups achieved three-dimensional spinal corrections and significantly increased postoperative rates of patients with T6-T8 TK apex (P = .006 for notch-free rods and P = .008 for notched rods). The rod deformation angle at the concave side was significantly lower in the notch-free rods than in the notched rods (P < .001). The notch-free, pre-bent rod can maintain its curvature, leading to better correction or maintenance of TK after anatomical spinal correction surgery than the conventional notched rod. These results suggest the potential benefits of anatomically designed notch-free, pre-bent rods over conventional, manually bent rods.

Background Context: Timely intervention in growing individuals, such as brace treatment, relies on early detection of adolescent idiopathic scoliosis (AIS). To this end, several screening methods have been implemented. However, these methods have limitations in predicting the Cobb angle., Purpose: This study aimed to evaluate the performance of a three-dimensional depth sensor imaging system with a deep learning algorithm, in predicting the Cobb angle in AIS., Study Design: Retrospective analysis of prospectively collected, consecutive, nonrandomized series of patients at five scoliosis centers in Japan., Patient Sample: One hundred and-sixty human subjects suspected to have AIS were included., Outcome Measures: Patient demographics, radiographic measurements, and predicted Cobb angle derived from the deep learning algorithm were the outcome measures for this study., Methods: One hundred and sixty data files were shuffled into five datasets with 32 data files at random (dataset 1, 2, 3, 4, and 5) and five-fold cross validation was performed. The relationships between the actual and predicted Cobb angles were calculated using Pearson's correlation coefficient analyses. The prediction performances of the network models were evaluated using mean absolute error and root mean square error between the actual and predicted Cobb angles. The shuffling into five datasets and five-fold cross validation was conducted ten times. There were no study-specific biases related to conflicts of interest., Results: The correlation between the actual and the mean predicted Cobb angles was 0.91. The mean absolute error and root mean square error were 4.0° and 5.4°, respectively. The accuracy of the mean predicted Cobb angle was 94% for identifying a Cobb angle of ≥10° and 89% for that of ≥20°., Conclusions: The three-dimensional depth sensor imaging system with its newly innovated convolutional neural network for regression is objective and has significant ability to predict the Cobb angle in children and adolescents. This system is expected to be used for screening scoliosis in clinics or physical examination at schools., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to intraoperatively assess the effects of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis., Methods: Twenty patients who underwent posterior thoracic adolescent idiopathic scoliosis curve correction were evaluated. Compressive or distractive loaded force of 50N was applied on the handle of a compressor or distractor connected to the necks of pedicle screws inserted at T7 to T11. Segmental spinal flexibility rates were calculated based on the distance between screw heads under the loaded and unloaded conditions. In addition, the flexibility rates were obtained before and after multilevel facetectomy., Findings: Absolute flexibility rates of all segments significantly increased after multilevel facetectomy under both compressive and distractive forces (P < 0.01). The absolute change in the flexibility rate was significantly higher at the concave side than at the convex side under both compressive (P < 0.01) and distractive loaded forces (P = 0.046). No significant correlation was found between change in the flexibility rates and preoperative Cobb angle or preoperative curve flexibility., Interpretation: From a biomechanical point of view, multilevel facetectomy provides proper spinal flexibility to improve the correction rate of posterior adolescent idiopathic scoliosis surgery. The effects are higher at the concave side than at the convex side., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Adolescent idiopathic scoliosis (AIS) patients typically undergo surgical treatment as teenagers, follow-ups of >5 years are necessary to evaluate effects on peak pulmonary reserves. However, limited data is available regarding the long-term (>10 years) effects of surgical intervention on pulmonary function (PF) in patients with thoracic AIS., Objective: To provide long-term (>10 years) information on the PF after posterior spinal fusion for treating main thoracic AIS. We especially investigated whether surgical correction for AIS led to impairment of the PF., Methods: A total of 35 patients with main thoracic AIS treated with posterior spinal fusion were included. Radiographs and PF tests, which included measurements of absolute and percent-predicted values of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), were evaluated., Results: Mean age at surgery was 14.9 years (12-19 years). Mean follow-up period was 15.1 years (10-24 years). Although the final postoperative FVC and FEV1 absolute values were higher than the preoperative values, the differences were not statistically significant (p = 0.22 and p = 0.08, respectively). Percent-predicted FVC and FEV1 values between preoperative and final postoperative measurements were not statistically different (p = 0.63 and p = 0.29, respectively). However, for the patients who presented with pulmonary impairment preoperatively, both the FVC and FEV1 significantly increased at the final follow-up (p = 0.01 and p = 0.01, respectively)., Conclusions: Long-term results of AIS patients who underwent posterior spinal fusion in main thoracic curves demonstrated absolute and percent-predicted PF test values similar to preoperative measurements; thus, indicating that posterior spinal fusion did not decrease PF 15 years after the initial surgery. Instead, patients with severe preoperative pulmonary impairment might show some degree of improvement after surgery., Competing Interests: The authors have declared that no competing interests exist.

Background: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity., Methods: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments., Results: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype., Conclusions: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

Adolescent idiopathic scoliosis is the most ordinary pediatric spinal disease that causes a three-dimensional deformity. Early detection of this potentially progressive deformity is considered crucial. The purpose of the present study was to report the potential for accurately diagnosis of adolescent idiopathic scoliosis using a newly developed, automated, noninvasive asymmetry-recognition system for the surface of the human back using a three-dimensional depth sensor. We included 170 subjects with suspected adolescent idiopathic scoliosis in this study. Outcomes measured included patient demographics, Cobbe angles from radiographic measurements, and asymmetry indexes. The coefficient of correlation between the asymmetry index and the Cobb angle was 0.85. For the prediction of scoliosis >10°, the area under the curve was 0.98, sensitivity was 0.97, specificity was 0.93, positive predictive value was 0.99, negative predictive value was 0.72, accuracy was 0.97, positive likelihood ratio was 13.55, and negative likelihood ratio was 0.04. The posterior test probability for the positive screen >10° was 98.9% if the asymmetry index was >1.268, three times in a row. This novel system automatically evaluated the back asymmetry. Therefore, this study demonstrates the outstanding discriminative ability of this newly developed system for deciding whether an examinee should undergo additional radiography to define scoliosis. This system can be used as an alternative to the forward bend test and scoliometer measurement in clinics. Future studies should seek to confirm these findings in a larger group and involve mass school scoliosis screening programs within the context of a multicenter trial.

Idiopathic scoliosis is the most common pediatric musculoskeletal disorder that causes a three-dimensional deformity of the spine. Early detection of this progressive aliment is essential. The aim of this study is to determine outcomes using a newly developed automated asymmetry-evaluation system for the surface of the human back using a three-dimensional depth sensor. Seventy-six human subjects suspected to have idiopathic scoliosis were included in this study. Outcome measures include patient demographics, radiographic measurements, and asymmetry indexes defined in the automated asymmetry-recognition system. The mean time from scanning to analysis was 1.5 seconds. For predicting idiopathic scoliosis of greater than 25°, the area under the curve was 0.96, sensitivity was 0.97, and specificity was 0.88. The coefficient of variation for repeatability analyses using phantom models was 1-4%. The intraclass correlation coefficient obtained for intra-observer repeatability for human subjects was 0.995. The system three-dimensionally scans multiple points on the back, enabling an automated evaluation of the back's asymmetry in a few seconds. This study demonstrated discriminative ability in determining whether an examinee requires an additional x-ray to confirm diagnosis.

OBJECTIVEThe aim of this retrospective study was to analyze the influence of upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on the long-term postoperative results of patients with main thoracic (MT) adolescent idiopathic scoliosis (AIS).METHODSTwenty-five patients had been treated surgically for AIS with a Lenke type 1 curve and had been followed up for a mean period of 18.2 years. Radiographic parameters, pulmonary function measurements, and clinical outcomes were compared between the patients (n = 15) with UIV translation < 20 mm and those (n = 10) with UIV translation ≥ 20 mm at the final follow-up. Correlations between UIV translation and radiographic or pulmonary function parameters were analyzed.RESULTSPatients with ≥ 20 mm UIV translation at the final follow-up had a significantly larger preoperative UIV translation than that in the patients with < 20 mm UIV translation at follow-up. The former group also had a significantly lower correction rate of the MT curve, higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005, and 0.025, respectively) at the final follow-up. The Scoliosis Research Society (SRS)-30 Questionnaire scores were equivalent between the two groups. Correlation analysis showed that the following parameters were significantly associated with UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1 second (r = -0.455, p = 0.033).CONCLUSIONSThe UIV translation should be considered an important factor that influences postoperative results. In MT AIS patients whose preoperative upper end vertebra (UEV) is distant from the C7PL, the UIV should be selected above the UEV to prevent large UIV translation at the postoperative follow-up.

Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional deformity of the spine. Although rod curvature could play an important role in anatomical spinal reconstruction in patients with thoracic AIS, intraoperative contouring of the straight rod induces notches into the rod, leading to decreased fatigue strength. Here, we analyzed pre-bent rod geometries from 46 intraoperative tracings of the rod geometry, which can provide anatomical spinal reconstruction in patients with thoracic AIS. The center point clouds of the rod shapes were extracted and approximated as arcs and straight lines. The difference between the center point clouds were evaluated using the iterative closest point methods. When the rod shapes were divided into six groups based on length followed by hierarchical cluster analysis, 10 representative rod shapes were obtained with a difference value of 5 mm. Thus, we identified optimized rod shapes to guide anatomical spinal reconstruction for thoracic AIS, which will reduce not only the risk of rod breakage but also operation time, leading to decreased patient burden. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3219-3224, 2018., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown., Methods: We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole-exome sequencing., Results: We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease-causing variants were identified in other patients, however. LFNG encodes a GlcNAc-transferase. The LFNG variants showed loss of their enzyme function., Conclusions: A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Study Design: A prospective, nonrandomized study., Objective: The aim of this study was to assess surgical outcomes of multilevel facetectomy and rod curvature with simultaneous double-rod rotation technique for anatomical spinal reconstruction in thoracic adolescent idiopathic scoliosis (AIS)., Summary of Background Data: Although some surgical techniques maintain or restore thoracic kyphosis (TK), next-generation strategies for thoracic AIS should include corrections in three anatomical planes., Methods: The study included 39 consecutive patients with Lenke 1 or Lenke 2 thoracic AIS treated at our institution. After all-level facetectomy at instrumentation level, except for the lowest intervertebral segment, two rods were identically bent to guide postoperative anatomical TK without reference to the intraoperative coronal alignment of the AIS deformity. Outcome measures included patient demographics, radiographic measurements, and Scoliosis Research Society (SRS) questionnaire scores., Results: After 2 years of follow-up, the average main thoracic Cobb angle correction rate was 83.5%, and the final correction loss was 2.2°. The average preoperative TK (T5-T12) significantly increased from 13.2° to 24.6° (P < 0.001) at final follow-up. The percentage of patients with a T6-T8 location of the TK apex significantly increased from 51.3% preoperatively to 87.2% at final follow-up. The average preoperative vertebral rotation angle significantly decreased from 18.7° to 12.8° postoperatively (P < 0.001). The average preoperative total SRS questionnaire score significantly increased from 3.5 to 4.5 (P < 0.001) at final follow-up. There was no implant breakage and vascular and neurologic complications, with all patients demonstrating solid fusion at final follow-up., Conclusion: Multilevel facetectomy and rod curvature play an important role in anatomical spinal reconstruction in patients with thoracic AIS. From the spatiotemporal point of view, four-dimensional correction could be actively performed by rod curvature under multilevel facetectomy and is expected to obtain an anatomical thoracic spine postoperatively, indicating that an anatomically designed rod could be supplied as a pre-bent rod., Level of Evidence: 3.

Study Design: Case-only study., Objective: The aim of this study was to confirm the association of rs11190870 with adolescent idiopathic scoliosis (AIS) severity in Japanese patients with AIS., Summary of Background Data: Although the association of rs11190870 with AIS susceptibility is replicated in multiple ethnics, the association of rs11190870 with curve severity is controversial. Since the previous studies are of small, we performed a replication study using far larger number of patients than previous studies., Methods: A total of 1860 Japanese patients with AIS who had reached skeletal maturity or undergone surgical fusion were included in the study. We evaluated the association between rs11190870 and AIS progression for the entire group, and then for patients grouped according to a severe curve (a Cobb angle of ≥40°) or mild curve (a Cobb angle <30°). Because braces could affect the results of the present study, patients in the mild-curve group were divided according to whether or not they had worn a brace. We then evaluated associations between rs11190870 genotype and curve severity in these groups., Results: The mean Cobb angles were 54.8° ± 12.1° in the severe-curve group and 24.4° ± 4.0° in the mild-curve group. The difference in rs11190870 risk-allele frequency between the severe- and mild-curve groups was evaluated. No significant differences were observed. We then examined the association of rs11190870 risk-allele frequency between patients in the mild- and severe-curve groups using the χ test for three models, and found a marginal association between rs11190870 and curve severity in the dominant model (P = 0.035, odds ratio = 1.51)., Conclusion: We found no association between rs11190870 and curve severity using the criteria of previous study. However, we found a marginal association between rs11190870 and curve severity. Large-scale replication studies that consider skeletal maturity and brace history, including replication studies in other ethnic groups, would be helpful for clarifying the association., Level of Evidence: 4.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting millions of children. Since treatment and prognosis of AIS depend on curve progression, identifying factors related to AIS curve progression is important in its management. Although several genetic loci for AIS occurrence are reported, no locus for curve progression has been identified. To identify genes associated with AIS progression, we conducted a genome-wide association study followed by a replication study using a total of 2,543 AIS subjects who were evaluated for the curve progression. We identified a significantly associated locus on chromosome 11q14.1 (P = 1.98 × 10-9, odds ratio = 1.56). In silico and in vitro analyses identified a functional variant, rs35333564 in MIR4300HG, the host gene of a microRNA, MIR4300. The genomic region containing rs35333564 had enhancer activity, which was decreased in its risk allele. Our data suggest that decrease of MIR4300 is related to AIS progression., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS., (© 2017 WILEY PERIODICALS, INC.)

Background Context: Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery., Purpose: This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve., Study Design: A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken., Patient Sample: Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included., Outcome Measures: Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study., Methods: Multiple stepwise linear regression analysis was conducted between change in TK (T5-T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK<15° group defined by preoperative TK below the mean degree of TK for the entire cohort (<15°) and the TK≥15° group, defined by preoperative TK above the mean degree of kyphosis (≥15°). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest., Results: The average preoperative TK was 14.0°, which improved significantly to 23.1° (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK <15° group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK ≥15° group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r=0.030, p=.880). Furthermore, in patients with preoperative TK<15°, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402)., Conclusions: In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Flattening of the preimplantation rod contour in the sagittal plane influences thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. The effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour have not been documented. This study aimed to evaluate the effects of multilevel facetectomy and screw density on changes in spinal rod contour from before implantation to after surgical correction of thoracic curves in patients with AIS prospectively. The concave and convex rod shapes from patients with thoracic AIS (n = 49) were traced prior to insertion. Postoperative sagittal rod shape was determined by computed tomography. The angle of intersection of the tangents to the rod end points was measured. Multiple stepwise linear regression analysis was used to identify variables independently predictive of change in rod contour (Δθ). Average Δθ at the concave and convex side were 13.6° ± 7.5° and 4.3° ± 4.8°, respectively. The Δθ at the concave side was significantly greater than that of the convex side (P < 0.0001) and significantly correlated with Risser sign (P = 0.032), the preoperative main thoracic Cobb angle (P = 0.031), the preoperative TK angle (P = 0.012), and the number of facetectomy levels (P = 0.007). Furthermore, a Δθ at the concave side ≥14° significantly correlated with the postoperative TK angle (P = 0.003), the number of facetectomy levels (P = 0.021), and screw density at the concave side (P = 0.008). Rod deformation at the concave side suggests that corrective forces acting on that side are greater than on the convex side. Multilevel facetectomy and/or screw density at the concave side have positive effects on reducing the rod deformation that can lead to a loss of TK angle postoperatively., Competing Interests: The authors have declared that no competing interests exist.

Aims: The aims of our study were to provide long-term information on the behaviour of the thoracolumbar/lumbar (TL/L) curve after thoracic anterior correction and fusion (ASF) and to determine the impact of ASF on pulmonary function., Patients and Methods: A total of 41 patients (four males, 37 females) with main thoracic (MT) adolescent idiopathic scoliosis (AIS) treated with ASF were included. Mean age at surgery was 15.2 years (11 to 27). Mean follow-up period was 13.5 years (10 to 18)., Results: For the TL/L curve, the mean curve flexibility evaluated with supine pre-operative bending radiographs was 78.6% (standard deviation 16.5%), with no significant loss of correction observed. On comparing patients with an increase of the TL/L curve increase (> 4º, n = 9, 22%) to those without, significant differences were observed in the correction rate of the MT curve at the final follow-up (p = 0.011), correction loss of the MT curve (p = 0.003) and the proportion of patients who had semi-rigid instrumentation (p = 0.003). Pre-operative percentage predicted forced vital capacity (%FVC) was 80%, dropping to 72% at final follow-up (p < 0.001). The Scoliosis Research Society questionnaire score was not significantly different between patients with and without a TL/L curve increase (p = 0.606). Spontaneous lumbar curve correction (SLCC) was maintained up to 18 years following selective ASF in most patients and demonstrated significant correlation with maintenance of MT curve correction., Conclusion: Maintenance of MT curve correction using rigid instrumentation provided stable SLCC over time. An observed 8% decrease in %FVC indicates that ASF should be reserved for patients with no or only mild pulmonary impairment. Cite this article: Bone Joint J 2016;98-B:997-1002., (©2016 The British Editorial Society of Bone & Joint Surgery.)

Background Context: Consensus regarding the optimal upper vertebra to be instrumented during surgical treatment of Lenke 5C thoracolumbar and lumbar adolescent idiopathic scoliosis (AIS) remains limited., Purpose: This study aimed to assess whether a short fusion strategy is appropriate for correction of a Lenke 5C AIS curve by anterior correction and fusion surgery using dual-rod instrumentation., Study Design: This study design used retrospective comparative analysis of a prospectively collected, consecutive, non-randomized series of patients at a single institution., Patient Sample: Thirty consecutive patients with Lenke 5C AIS treated with anterior correction and fusion surgery using dual-rod instrumentation were included., Outcome Measures: Patient demographics, radiographic measurements, and Scoliosis Research Society-22 questionnaire (SRS-22) scores were the outcome measures for this study., Methods: Thirty patients were treated surgically for AIS with a Lenke 5C curve (mean age, 14.4 years [11-19 years)]) and followed up for a mean period of 17.2 years (12-23 years). Radiographical parameters and clinical outcomes were compared between patients treatment with the end vertebra (EV) instrumented (n=14) and those treated by short fusion (S group) with instrumentation starting at the vertebra one level caudal to the EV (n=16 patients). There were no study-specific biases related to conflicts of interest., Results: In the EV group, a mean preoperative Cobb angle of 56° was corrected to 5° after surgery and to 8° at the final follow-up. In the S group, a mean preoperative Cobb angle of 55° was corrected to 10° after surgery and 14° at the final follow-up. The mean correction rate at the final follow-up was significantly lower in the S group (74%) than in the EV group (86%; p=.020). The coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated using SRS-22 did not differ between the two groups., Conclusions: The short fusion strategy, which involves instrumentation of the vertebra one level caudal to the upper EV, can be considered as an alternative to the conventional strategy, which includes instrumentation of the upper EV, for treating Lenke 5C curves via anterior spinal fusion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: A total of 30 patients with thoracolumbar/lumbar adolescent idiopathic scoliosis (AIS) treated between 1989 and 2000 with anterior correction and fusion surgery using dual-rod instrumentation were reviewed., Patients and Methods: Radiographic parameters and clinical outcomes were compared among patients with lowest instrumented vertebra (LIV) at the lower end vertebra (LEV; EV group) (n = 13) and those treated by short fusion (S group), with LIV one level proximal to EV (n = 17 patients)., Results: The allocation of the surgical technique was determined by the flexibility of the TL/L curves and/or neutral vertebrae located one level above LEV as determined on preoperative radiographs. If these requirements were met a short fusion was performed. The mean follow-up period was 21.4 years (16 to 27). The mean correction rate at final follow-up was significantly lower in the S group (74 sd 11%) than in the EV group (88 sd 13%) (p = 0.004).Coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, and clinical outcomes evaluated by the Scoliosis Research Society-22 questionnaire scores were equivalent between the two groups., Conclusion: Short fusion strategy, which uses LIV one level proximal to LEV can be considered as an alternative to the conventional strategy, which includes LEV in the fusion, when highly flexible TL/L curves are confirmed and/or neutral vertebrae are located one level above LEV in patients with thoracolumbar/lumbar AIS curves., Take Home Message: Short fusion strategy can be considered as an alternative to the conventional strategy in patients with thoracolumbar/lumbar AIS curves undergoing anterior spinal fusion with dual-rod instrumentation. Cite this article: Bone Joint J 2016;98-B:402-9., (©2016 The British Editorial Society of Bone & Joint Surgery.)

Purpose: There is limited consensus on the optimal surgical strategy for double thoracic adolescent idiopathic scoliosis (AIS). Recent studies have reported that pedicle screw constructs to maximize scoliosis correction cause further thoracic spine lordosis. The objective of this study was to apply a new surgical technique for double thoracic AIS with rigid proximal thoracic (PT) curves and assess its clinical outcomes., Methods: Twenty one consecutive patients with Lenke 2 AIS and a rigid PT curve (Cobb angle ≥30º on side-bending radiographs, flexibility ≤30 %) treated with the simultaneous double-rod rotation technique (SDRRT) were included. In this technique, a temporary rod is placed at the concave side of the PT curve. Then, distraction force is applied to correct the PT curve, which reforms a sigmoid double thoracic curve into an approximate single thoracic curve. As a result, the PT curve is typically converted from an apex left to an apex right curve before applying the correction rod for PT and main thoracic curve., Results: All patients were followed for at least 2 years (average 2.7 years). The average main thoracic and PT Cobb angle correction rate at the final follow-up was 74.7 and 58.0 %, respectively. The average preoperative T5-T12 thoracic kyphosis was 9.3°, which improved significantly to 19.0° (p < 0.0001) at the final follow-up. Although 71 % patients had preoperative level shoulders or a positive radiographic shoulder height, all patients had mildly imbalanced or balanced shoulders at the final follow-up. The average preoperative main thoracic apical vertebral rotation angle of 20.7° improved significantly after surgery to 16.4° (p = 0.0046), while the average preoperative total SRS questionnaire score of 3.7 improved significantly to 4.4 (p = 0.0012) at the final follow-up., Conclusions: Radiographic findings and patient outcomes were satisfactory. Thoracic kyphosis can be maintained or improved, while coronal and axial deformities can be corrected using SDRRT for Lenke 2 AIS with a rigid PT curve.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS., (Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective analysis of a prospectively collected, consecutive, nonrandomized series of patients., Objective: To assess the surgical outcomes of the simultaneous double-rod rotation technique for treating Lenke 1 thoracic adolescent idiopathic scoliosis (AIS)., Summary of Background Data: With the increasing popularity of segmental pedicle screw spinal reconstruction for treating AIS, concerns regarding the limited ability to correct hypokyphosis have also increased., Methods: A consecutive series of 32 patients with Lenke 1 main thoracic AIS treated with the simultaneous double-rod rotation technique at our institution was included. Outcome measures included patient demographics, radiographical measurements, and Scoliosis Research Society questionnaire scores., Results: All 32 patients were followed up for a minimum of 2 years (average, 3.6 yr). The average main thoracic Cobb angle correction rate and the correction loss at the final follow-up were 67.8% and 3.3°, respectively. The average preoperative thoracic kyphosis (T5-T12) was 11.9°, which improved significantly to 20.5° (P < 0.0001) at the final follow-up. An increase in thoracic kyphosis was significantly correlated with an increase in lumbar lordosis at the final follow-up (r = 0.42). The average preoperative vertebral rotation angle was 19.7°, which improved significantly after surgery to 14.9° (P = 0.0001). There was no correlation between change in thoracic kyphosis and change in apical vertebral rotation (r =-0.123). The average preoperative total Scoliosis Research Society questionnaire score was 3.0, which significantly improved to 4.4 (P < 0.0001) at the final follow-up. Throughout surgery and even after, there were no instrumentation failures, pseudarthrosis, infection of the surgical site, or clinically relevant neurovascular complications., Conclusion: The simultaneous double-rod rotation technique for treating Lenke 1 AIS provides significant sagittal correction of the main thoracic curve while maintaining sagittal profiles and correcting coronal and axial deformities., Level of Evidence: 4.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

Study Design: A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS)., Objective: To determine whether the association of 53 SNPs with curve progression reported in white patients with AIS are replicated in Japanese patients with AIS., Summary of Background Data: Predicting curve progression is important in clinical practice of AIS. The progression of AIS is reported to be associated with a number of genes. Associations with 53 SNPs have been reported, and the SNPs are used for a progression test in white patients with AIS; however, there has been no replication study for their association., Methods: We recruited 2117 patients with AIS with 10° or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50° for skeletally mature subjects and more than 40° for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50° or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups., Results: We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. Their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs., Conclusion: The associations of the 53 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression., Level of Evidence: N/A.

Study Design: Retrospective review., Objective: To assess the long-term outcomes of anterior spinal fusion (ASF) for treating thoracic adolescent idiopathic scoliosis (AIS)., Summary of Background Data: Although ASF is reported to provide good coronal and sagittal correction of the main thoracic (MT) AIS curves, the long-term outcomes of ASF is unknown., Methods: A consecutive series of 25 patients with Lenke 1 MT AIS were included. Outcome measures comprised radiographical measurements, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores (preoperative SRS-30 scores were not documented). Postoperative surgical revisions and complications were recorded., Results: Twenty-five patients were followed-up for 12 to 18 years (average, 15.2 yr). The average MT Cobb angle correction rate and the correction loss at the final follow-up were 56.7% and 9.2°, respectively. The average preoperative instrumented level of kyphosis was 8.3°, which significantly improved to 18.6° (P = 0.0003) at the final follow-up. The average percent-predicted forced vital capacity and forced expiratory volume in 1 second were significantly decreased during long-term follow-up measurements (73% and 69%; P = 0.0004 and 0.0016, respectively). However, no patient had complaints related to pulmonary function. The average total SRS-30 score was 4.0. Implant breakage was not observed. All patients, except 1 who required revision surgery, demonstrated solid fusion. Late instrumentation-related bronchial problems were observed in 1 patient who required implant removal and bronchial tube repair, 13 years after the initial surgery., Conclusion: Overall radiographical findings and patient outcome measures of ASF for Lenke 1 MT AIS were satisfactory at an average follow-up of 15 years. ASF provides significant sagittal correction of the main thoracic curve with long-term maintenance of sagittal profiles. Percent-predicted values of forced vital capacity and forced expiratory volume in 1 second were decreased in this cohort; however, no patient had complaints related to pulmonary function.

Background: Anterior spinal fusion with instrumentation is used for the treatment of thoracolumbar/lumbar scoliosis. The aim of this long-term, retrospective, hospital-based cohort study was to determine the outcomes of anterior dual-rod instrumentation in a consecutive series of patients with thoracolumbar/lumbar adolescent idiopathic scoliosis managed by a single surgeon at a single institution., Methods: A consecutive series of thirty-two patients with Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis were included. Outcome measures included patient demographics, radiographic measurements, adjacent-segment degeneration, pulmonary function, and Scoliosis Research Society outcome instrument (SRS-30) scores. Perioperative and postoperative complications were recorded., Results: Thirty patients were followed for a mean of 17.2 years (range, twelve to twenty-three years). The mean thoracolumbar/lumbar Cobb angle correction rate and correction loss at the time of the latest follow-up were 79.8% and 3.4°, respectively. The average percent-predicted forced vital capacity and forced expiratory volume in one second were 91.8% and 81.8%, respectively. The average total SRS-30 score was 4.2. Mild degeneration below the fusion mass was observed in 23% of the patients. No instrumentation failure, pseudarthrosis, surgical site infection, or clinically relevant neurovascular complications were observed. Two patients required surgical revision with posterior spinal instrumentation, one because of subjacent disc wedging and the other because of progression of the thoracic curve deformity., Conclusions: Radiographic findings, pulmonary function, and clinical measures were satisfactory at the time of follow-up, at a minimum of twelve years. Anterior dual-rod instrumentation remains a useful surgical treatment for Lenke type-5C thoracolumbar/lumbar adolescent idiopathic scoliosis.

Study Design: A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS)., Objective: To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS., Summary of Background Data: AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them., Methods: We recruited 2117 patients with AIS with a Cobb angle of 10° or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40° or greater were included in the progression group, and those whose scoliotic curves were less than 30° and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype., Results: We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs., Conclusion: The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.

Object: Use of computer-assisted spine surgery (CASS) technologies, such as navigation systems, to improve the accuracy of pedicle screw (PS) placement is increasingly popular. Despite of their benefits, previous CASS systems are too expensive to be ubiquitously employed, and more affordable and portable systems are desirable. The aim of this study was to introduce a novel and affordable computer-assisted technique that 3-dimensionally visualizes anatomical features of the pedicles and assists in PS insertion. The authors have termed this the 3D-visual guidance technique for inserting pedicle screws (3D-VG TIPS)., Methods: The 3D-VG technique for placing PSs requires only a consumer-class computer with an inexpensive 3D DICOM viewer; other special equipment is unnecessary. Preoperative CT data of the spine were collected for each patient using the 3D-VG TIPS. In this technique, the anatomical axis of each pedicle can be analyzed by volume-rendered 3D models, as with existing navigation systems, and both the ideal entry point and the trajectory of each PS can be visualized on the surface of 3D-rendered images. Intraoperative guidance slides are made from these images and displayed on a TV monitor in the operating room. The surgeon can insert PSs according to these guidance slides. The authors enrolled 30 patients with adolescent idiopathic scoliosis (AIS) who underwent posterior fusion with segmental screw fixation for validation of this technique., Results: The novel technique allowed surgeons, from office or home, to evaluate the precise anatomy of each pedicle and the risks of screw misplacement, and to perform 3D preoperative planning for screw placement on their own computer. Looking at both 3D guidance images on a TV monitor and the bony structures of the posterior elements in each patient in the operating theater, surgeons were able to determine the best entry point for each PS with ease and confidence. Using the current technique, the screw malposition rate was 4.5% in the thoracic region in corrective surgery for AIS., Conclusions: The authors found that 3D-VG TIPS worked on a consumer-class computer and easily visualized the ideal entry point and trajectory of PSs in any operating theater without costly special equipment. This new technique is suitable for preoperative planning and intraoperative guidance when performing reconstructive surgery with PSs.

Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2-3% of school-age children worldwide(1). Genetic factors have been implicated in its etiology(2). Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 × 10(-19); odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin-like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR-based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese., (Copyright © 2011 Orthopaedic Research Society.)

Adolescent idiopathic scoliosis (AIS) is a common disorder with a strong genetic predisposition. Associations between AIS and common single nucleotide polymorphisms (SNPs) in estrogen receptor genes have been reported. rs9340799 in the gene for estrogen receptor α (ESR1) is reported to be associated with curve severity in Japanese and with AIS predisposition and curve severity in Chinese. In addition, rs1256120 in the gene for estrogen receptor β (ESR2) is reported to be associated with AIS predisposition and curve severity in Chinese. However, the sample sizes of these previous studies were small, and the associations of these SNPs have not been replicated. To examine the association between AIS and estrogen receptor genes, we investigated the association of rs9340799 and rs1256120 with AIS predisposition and curve severity using a large Japanese population, consisting of 798 AIS patients and 637 sex-matched controls. We found no association of either SNP with AIS predisposition or curve severity in the Japanese population. Considering the statistical power of the present study and the limitations of the previous reports, we conclude that the associations of rs9340799 and rs1256120 with AIS predisposition and curve severity are negative., (Copyright © 2010 Orthopaedic Research Society.)

The authors present a new posterior correction technique consisting of simultaneous double-rod rotation using 2 contoured rods and polyaxial pedicle screws with or without Nesplon tapes. The purpose of this study is to introduce the basic principles and surgical procedures of this new posterior surgery for correction of adolescent idiopathic scoliosis. Through gradual rotation of the concave-side rod by 2 rod holders, the convex-side rod simultaneously rotates with the the concave-side rod. This procedure does not involve any force pushing down the spinal column around the apex. Since this procedure consists of upward pushing and lateral translation of the spinal column with simultaneous double-rod rotation maneuvers, it is simple and can obtain thoracic kyphosis as well as favorable scoliosis correction. This technique is applicable not only to a thoracic single curve but also to double major curves in cases of adolescent idiopathic scoliosis.

Study Design: Retrospective study., Objectives: To compare the surgical outcomes of posterior translational correction and fusion using hybrid instrumentation systems with either sublaminar Nesplon tape or sublaminar metal wire to treat adolescent idiopathic scoliosis (AIS)., Summary of Background Data: Nesplon tape, which consists of a thread of ultra-high molecular weight polyethylene fibers, has advantages over metal wire: (1) its soft and flexible properties avoid neural damage and (2) its flat configuration avoids focal distribution of the stresses to lamina; however, the efficacy of Nesplon tape in the correction of spinal deformity is as yet, still unclear., Methods: Thirty AIS patients at a single institution underwent posterior correction and fusion using hybrid instrumentation containing hook, pedicle screw, and either sublaminar polyethylene taping (15) or sublaminar metal wiring (15). Patients were evaluated preoperatively, immediately after surgery, and at a 2-year follow-up according to the radiographic changes in curve correction, operating time, intraoperative blood loss, complications, and the Scoliosis Research Society patient questionnaire (SRS-24) score., Results: The average correction rate was 63.0% in the Nesplon tape group and 59.9% in the metal wire group immediately after surgery (P = 0.62). Fusion was obtained in all the patients without significant correction loss in both groups. There was no significant difference in operative time, intraoperative blood loss, and postoperative SRS-24 scores between the 2 groups. Complications were superficial skin infection in a single patient in the Nesplon tape group, and transient sensory disturbance in 1 patient and temporal superior mesenteric artery syndrome in another patient in the metal wire group., Conclusions: The efficacy of Nesplon tape in correction of deformity is equivalent to that of metal wire, and fusion was completed without significant correction loss. The soft and flexible properties and flat configuration of Nesplon tape make this a safe application for the treatment of AIS with bone fragility or with the fusion areas containing the spinal cord.

Study Design: The accuracy of pedicle screw placement was evaluated in posterior scoliosis surgeries with or without the use of computer-assisted surgical techniques., Objective: In this retrospective cohort study, the pedicle screw placement accuracy in posterior scoliosis surgery was compared between conventional fluoroscopic and computer-assisted surgical techniques., Summary of Background Data: There has been no study systemically analyzing the perforation pattern and comparative accuracy of pedicle screw placement in posterior scoliosis surgery., Methods: The 45 patients who received posterior correction surgeries were divided into 2 groups: Group C, manual control (25 patients); and Group N, navigation surgery (20 patients). The average Cobb angles were 73.7 degrees and 73.1 degrees before surgery in Group C and Group N, respectively. Using CT images, vertebral rotation, pedicle axes as measured to anteroposterior sacral axis and vertebral axis, and insertion angle error were measured. In perforation cases, the angular tendency, insertion point, and length abnormality were evaluated., Results: The perforation was observed in 11% of Group C and 1.8% in Group N. In Group C, medial perforations of left screws were demonstrated in 8 of 9 perforated screws and 55% were distributed either in L1 or T12. The perforation consistently occurred in pedicles in which those axes approached anteroposterior sacral axis within 5 degrees . The average insertion errors were 8.4 degrees and 5.0 degrees in Group C and Group N, respectively, which were significantly different (P < 0.02)., Conclusion: The medial perforation in Group C occurred around L1, especially when pedicle axis approached anteroposterior sacral axis. This consistent tendency was considered as the limitation of fluoroscopic screw insertion in which horizontal vertebral image was not visible. The use of surgical navigation system successfully reduced the perforation rate and insertion angle errors, demonstrating the clear advantage in safe and accurate pedicle screw placement of scoliosis surgery.