Benlong Shi

Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.

Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.

Integrated Multi-dimensional Maturity Assessments Predicting the High Risk Occurrence of Peak Angle Velocity During Puberty in Progressive Female Idiopathic Scoliosis

Study Design: A consecutive and prospective longitudinal study. Objective: To propose an integrated multidimensional maturity assessment that was designated as forming a reliable system precisely predicting the high-risk occurrence of peak angle velocity (PAV) in a group of progressive braced female idiopathic scoliosis (IS). Summary of Background Data: Scoliosis deterioration is believed to keep pace with the evolution of skeletal maturity during puberty. There is, however, a paucity of data in the literature regarding which unidimensional or multidimensional maturity assessment was most informational, and could be employed to predict the likelihood of significant curve progression. Materials and Methods: In this prospective study, braced IS girls with open triradiate cartilage were recruited and followed up at 6-month regular intervals. At each visit, the following data were collected: chronologic age, stage of menses, standing height, Cobb angle of the main curve, spine length, status of triradiate cartilage, Risser sign, and digital skeletal age (DSA) scores. The height velocity (HV) and spine length velocity (SLV), as well as the angle velocity (AV) of each visit were calculated. Finally, those with main curve progression of ≥5 degrees during brace treatment and with a minimum of 2-year follow-up covering the closure of the triradiate cartilage were recruited in this analysis, and their PAV was defined as the peak of AV curves during the whole follow-up period in puberty. Logistic regression analysis was used to evaluate the contribution of each measurement to the risk of PAV onset. Results: Thirty-six IS girls were finally recruited in the study, with an average age of 10.8 years at initial visit and 11.8 years at PAV. The average DSA score, spine length, standing height, and Cobb angle of main curve at PAV were 479.5, 326.7 mm, 150.8 cm, and 26.5 degrees, respectively. The average HV, AV, and SLV at PAV were 8.3 cm, 7.8 degrees, and 28.2 mm/y, respectively. The PAV occurred with Risser 0, 1, and 2 in 80.6%, 11.1%, and 8.3% of the IS girls and closed triradiate cartilages were found at PAV in all the girls. The logistic regression model revealed that the following variables contributed significantly to high-risk occurrence of PAV: chronologic age between 11 and 13 years [odds ratio (OR)=3.961; 95% confidence interval (CI), 1.023–15.342], Risser 0 (OR=14.261; 95% CI, 1.167–65.528), closed triradiate cartilage (OR=6.590; 95% CI, 1.612–26.943), DSA scores between 400 and 500 (OR=6.042; 95% CI, 1.282–28.482), HV>6 cm/y (OR=5.711; 95% CI, 1.105–29.526), Cobb angle of main curve >30 degrees (OR=5.492; 95% CI, 1.151–26.207) and SLV>20 mm/y (OR=5.973; 95% CI, 1.546–23.071). Conclusions: Integrated multidimensional maturity assessments, defined as chronologic age between 11 and 13 years, modified Risser 0, DSA scores between 400 and 500, HV>6 cm/y, and SLV>20 mm/y, combined with preexisting scoliotic curve >30 degrees, were prone to increase the risk of entering the rapid curve acceleration phase in progressive IS girls.

Spinal growth velocity versus height velocity in predicting curve progression in peri-pubertal girls with idiopathic scoliosis

BackgroundHeight velocity (HV) is traditionally used to monitor the residual growth potential in idiopathic scoliosis (IS). The temporal timing of rapid increase in standing height often does not match exactly that of the increase in spine height. The purposes of this study were to analyze the correlation between change of angle velocity (AV) vs the changes of spinal growth velocity (SGV) and HV, and the associated predictive value on curve progression in IS.MethodsPre-pubertal IS girls with single curve receiving standardized bracing treatment followed longitudinally with documented curve progression >5° were retrospectively reviewed. The age, standing height, Cobb angle (main curve), spinal length, Risser sign, HV, SGV and AV at each visit were measured and calculated. The visit with the highest AV value of each patient was selected for the final analysis and correlated with the corresponding peak height velocity (PHV) and peak spinal growth velocity (PSGV).ResultsSixty-two IS girls were reviewed. Chi-square test revealed PSGV contributed more to the highest AV than PHV (P = 0.001). Pearson correlation analysis demonstrated that AV was correlated with SGV (r = 0.454, P < 0.001) and HV (r = 0.280, P = 0.027). Multiple linear regression analysis showed that high AV was better predicted by higher SGV (B = 0.321, P = 0.007) rather than higher HV (B = 0.259, P = 0.362) (R = 0.467).ConclusionsVariations of spinal growth velocity exerted more direct influence over changes in angle velocity as compared with height velocity. High spinal growth velocity predisposed to more rapid curve progression in patients with idiopathic scoliosis.

How Does the Supine MRI Correlate With Standing Radiographs of Different Curve Severity in Adolescent Idiopathic Scoliosis

Study Design. A retrospective study. Objective. To study how the supine magnetic resonance image (MRI) correlates with standing radiographs of different curve severity in adolescent idiopathic scoliosis (AIS). Summary of Background Data. Linear correlation between Cobb angles measured on supine MRI and standing radiographs has been identified. However, the effects of different curve severity on the correlation have not been studied in depth. Methods. Girls with AIS with standing radiographs and supine MRI were reviewed. From standing radiographs, all structural and nonstructural Cobb angles were measured. For those with simultaneous lateral radiographs, thoracic kyphosis (TK) and lumbar lordosis (LL) angles were measured. On supine MRI, the coronal Cobb angles, TK and LL were measured accordingly. The coronal Cobb angles were divided into 3 groups based on values measured on standing radiographs: mild group for Cobb angles less than 20°, moderate group for 20° to 40°, and severe group for more than 40°. Correlation was analyzed using scatter plot. Results. Eighty patients with AIS with 122 coronal curves were reviewed. On standing radiographs, the coronal Cobb angles were 14.7°± 3.2°, 28.2°± 5.1°, and 54.9°± 11.3° for mild, moderate, and severe groups. On supine MRI, the Cobb angles averaged 10.1°± 5.6°, 20.0°± 6.3°, and 49.4 ± 12.3° for each group, respectively. TK were 16.3 ± 9.1° and 11.8 ± 6.1° for radiographs and MRI (P < 0.001), whereas the LL averaged 45.5 ± 12.2° and 39.5 ± 10.5° for radiographs and MRI (P < 0.001). Cobb angles measured on standing radiographs and supine MRI were linearly correlated with the adjusted R2 being 0.0627, 0.2118, and 0.7999 for the mild, moderate, and severe groups. Conclusion. Cobb angles measured on supine MRI were linearly correlated with Cobb angles measured on standing radiographs and the correlation was more reliable in those with Cobb angles more than 40°. Therefore, the supine MRI could serve as a reliable alternative to standing radiographs in the assessment of Cobb angles more than 40° in AIS. Level of Evidence: 3

Spine velocity provides more accurate assessment of curve progression than height velocity in progressive female idiopathic scoliosis undergoing bracing treatment

of growth velocity curves. Multiple linear regression analysis was used to analyze the contributions of each maturity assessments to AV, while logistic regression model was constructed to identify the high risk factors of AV more than 5° per year. Results Thirty IS girls were included in this study. Correlation was found between SV and HV (r=0.314, P=0.001). AV was significantly correlated with SV (r=0.414, P<0.001) and HV (r=0.275, P=0.005), respectively. The multiple linear regression analysis showed that AV was influenced by SV (B=0.199, P=0.001) instead of HV (B=0.187, P=0.354). The logistic regression analysis demonstrated that PSV (OR=5.052, P=0.001) rather than PHV (OR=1.979, P=0.144) was the high risk indicator for the occurrence of AV more than 5° per year. Conclusions Variations of curve progressive velocity were influenced more directly by SV rather than HV, and congruously onset of PSV were endowed with the high risk of the occurrence of AV more than 5° per year in IS girls with curve progression of 10° or more, indicating the high clinical value of measurement of spinal growth in the treatment of IS.

Does the Position of the Aorta Change With the Altered Body Position in Ankylosing Spondylitis Patients With Thoracolumbar Kyphosis?: A Magnetic Resonance Imaging Investigation

Study Design: A prospective magnetic resonance imaging study. Objective: To quantitatively explore the differences in the anatomic position of the aorta relative to the spine between supine and prone positions in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. Summary of Background Data: Aortic complications may occur during the lumbar spine osteotomy in correcting thoracolumbar kyphosis secondary to AS, and a clear understanding of the spatial relationship between the aorta and the vertebrae is essential to prevent these iatrogenic complications. However, previous anatomic study was performed with AS patients in the supine position, which was different from the prone position adopted in surgery. To date, no report has been published to investigate the mobility of the aorta relative to the vertebrae between supine and prone positions in AS patients with thoracolumbar kyphosis. Materials and Methods: From March 2013 to September 2014, 22 AS patients (21 males, 1 female) with thoracolumbar kyphosis with a mean age of 30.7 years (range, 19–46 y) were recruited. Magnetic resonance imaging examinations from T9 to L3 in both the supine and prone positions were performed, and the left pedicle-aorta (LtP-Ao) angle and LtP-Ao distance were measured at each level. The differences of these parameters between the 2 positions were compared by the paired sample t test, and the relationships between the shifting of the aorta and the change of global kyphosis and lumbar lordosis were evaluated by the Pearson correlation coefficient. The level of significance (&agr;) was set at 0.05. Results: At T9–L3 levels, no significant difference was noted in LtP-Ao distances (43.78 vs. 44.42 mm; P=0.077) and LtP-Ao angles (0.82 vs. 0.22 degrees; P=0.053) between supine and prone positions. The correlation analysis also revealed no remarkable correlation between the change of LtP-Ao angle and increase of global kyphosis and lumbar lordosis in the prone position. Conclusions: There is no significant change of the relative positions between the aorta and the vertebrae at T9–L3 levels after the patient turned to a prone position, which implied that the mobility and range of motion of the aorta is limited in advanced stage of AS.

Both Bilateral Breast Volume Discrepancy and Asymmetric Anterior Chest Wall Shape Contribute to the Unsightly Breast Contour in Female Right Thoracic Idiopathic Scoliosis.

Study design: A retrospective radiographic study. Objective: To evaluate the asymmetry of breast volume (BV) and shape in female adolescent idiopathic scoliosis (AIS) patients and to define their relationship with deformed components of the anterior chest wall and curved spine. Summary of Background Data: The higher incidence of asymmetric breast development in AIS was described by prior studies. However, the interplay between scoliosis curve magnitude and severity of breast asymmetry (BA) are unknown. Methods: A total of 73 surgically treated female right thoracic AIS patients classified as Lenke type I were enrolled in this study, with the average Cobb angle being 52.08±11.68 degrees. The Image J software was utilized to calculate BV. Both concave and convex radiographic parameters of breast shape were measured including the extraversion angle (EA), the coverage angle (CA), the axial breast height, the vertical breast height (VBH), and the nipple-to-sternum distance. The inclination angles of the concave and convex anterior chest wall were also assessed. BA was calculated according to the formula as follows: BA=(concave−convex)×BV/[(concave+convex)×BV]/2. The measurements of spinal deformity parameters included the Cobb angle, the RAsag angle, and the RAml angle. Paired t test was performed to analyze the asymmetry of breast shape, and Pearson correlation analysis was utilized to define the correlation between the breast shape, spinal deformity, and the inclination of anterior chest wall. Results: The concave BV, EA, axial breast height, and vertical breast height were significantly larger than those of the convex side (P<0.05), whereas the concave CA and the inclination angle of the anterior chest wall were significantly smaller than those of the convex side (P<0.05). No difference was detected between the concave and the convex nipple-to-sternum distance (P>0.05). The averaged BA was 11.4%, with the ratio of asymmetry beyond 10% being 52.1%. No statistically significant relationships between BA and Cobb angle, RAsag angle, RAml angle were detected (P>0.05). The inclination angle of the anterior chest wall demonstrated significant correlation with EA (P<0.001) and CA (P<0.001), respectively. Conclusions: The incidence of BA in AIS is notable, with the concave breast being larger, more extroversive, and more concentrated than the convex breast. The discrepancy between concave and convex anterior chest wall inclination bound to scoliosis could have a major influence on breast orientation and profile, suggesting a synergistic role of anterior chest wall deformity and bilateral BV discrepancy in the formation of BA.

SRS-Schwab Grade 4 osteotomy for congenital thoracolumbar kyphosis: a minimum of 2 years follow-up study

BACKGROUND CONTEXT Several osteotomy techniques including pedicle subtraction osteotomy and vertebral column resection have been employed in the correction of congenital kyphosis (CK) and satisfying outcomes have been demonstrated. However, the Scoliosis Research Society (SRS)-Schwab Grade 4 osteotomy, defined as resection of posterior elements, partial vertebral body, and superior adjacent disc, is rarely reported in the treatment of CK. PURPOSE The present study aimed to evaluate the efficiency and safety of SRS-Schwab Grade 4 osteotomy in patients with CK, and to propose its optimal indication. STUDY DESIGN This is a retrospective analysis of clinical and radiographic outcomes of patients with CK undergoing SRS-Schwab Grade 4 osteotomy. PATIENTS SAMPLE Patients with thoracolumbar CK undergoing SRS-Schwab Grade 4 osteotomy from January 2010 to May 2015 followed up for at least 2 years were retrospectively reviewed. OUTCOME MEASURES The thoracic kyphosis, lumbar lordosis, segmental kyphosis (SK), sagittal vertical axis (SVA), pelvic incidence, pelvic tilt, and sacral slope were measured on lateral spinal x-rays. Patients were required to fulfill the SRS-22 questionnaire at preoperation and the last follow-up. MATERIALS AND METHODS The sagittal spinal-pelvic parameters were assessed at preoperation, postoperation, and last follow-up. The comparison between preoperation and postoperation was performed by paired samples t test. RESULTS A total of 38 patients with CK (17 male and 21 female) with an average age of 16.5±9.9 years were included. The mean operating time was 242.7±88.1 minutes and blood loss was 634.5±177.8 mL. The mean follow-up was 38.8±20.3 months. The SK was 49.5±11.7° at preoperation, 6.8±7.4° at postoperation (p<.001), and 8.0±8.1° at the last follow-up. No significant correction loss during follow-up was found in SK (p=.125). The SVA was improved from -36.0±18.3 mm at preoperation to 3.7±17.8 mm at postoperation (p<.001), and the correction was well maintained during follow-up (p=.113). Compared with preoperation, the mean postoperative scores of each domains of SRS-22 questionnaire improved at different levels. Intraoperative complications included one case with incidental dural tear and another with transient root injury. Proximal junctional kyphosis occurred in three patients at 6 months after operation and remained stable during the follow-up. At the last follow-up, all patients were identified to have achieved solid bony fusion. CONCLUSIONS The SRS-Schwab Grade 4 osteotomy, if selected appropriately, could provide satisfying correction of congenital kyphosis. The correction could be well maintained during the longitudinal follow-up.

A re-evaluation of the effects of dual growing rods on apical vertebral rotation in patients with early-onset scoliosis and a minimum of two lengthening procedures: a CT-based study

OBJECTIVE This study aimed to evaluate the correction results of traditional dual growing rods (DGRs) on axial rotation using CT scans and to further explore the relationships between axial and torso deformities in patients with early-onset scoliosis (EOS). METHODS Patients with EOS who were treated with traditional DGRs between January 2006 and December 2014 were retrospectively reviewed. Plain radiographs were used to assess the degree of coronal and sagittal deformity. The apical vertebral rotation (AVR) and rib hump (RH) were measured on CT scans at the apical vertebra. Pearson or Spearman rank correlation analyses were used to analyze the associations between spinal and torso deformities. RESULTS A total of 27 patients (10 boys and 17 girls, average age 6.5 ± 1.7 years) were enrolled in this study. The average number of lengthenings per patient was 5.0 ± 1.9, with a mean follow-up duration of 52.9 ± 18.2 months. The apical vertebral translation, apical vertebral body-rib ratio (AVB-R), AVR, and RH parameters were significantly decreased after the initial surgery (p < 0.05) but showed notable progression at the latest follow-up evaluation (p < 0.05). The preoperative AVR and its correction after index surgery were significantly correlated with the preoperative values as well as with the corrections of the major Cobb angle, AVB-R, and RH. During the follow-up period, significant correlations were found between the deterioration of AVR and the AVB-R and also between the deterioration of AVR and the RH from the initial surgery to the latest follow-up. CONCLUSIONS Significant AVR correction can be achieved by DGR techniques after the initial surgery. However, this technique weakly prevents the deterioration of AVR during the follow-up period.