Bangping Qian

Decreased circulating leptin level and its association with body and bone mass in girls with adolescent idiopathic scoliosis.

Study Design. A prospective study was designed to investigate the circulating leptin level in girls with adolescent idiopathic scoliosis (AIS). Objective. To determine the circulating leptin levels in AIS girls, and to investigate its associations with body mass and bone mass. Summary of Background Data. Abnormal growth pattern and osteopenia have been well documented in AIS patients throughout the peripubertal growth period. Leptin has been shown to regulate the growth of the whole body and bone particularly during childhood and adolescence. However, the circulating level of leptin, the relationships between leptin and lower body mass, and the relationships between leptin and lower bone mass in AIS patients remain unclear. Methods. One hundred twenty AIS girls and 80 healthy controls were recruited in this study. Measurements of anthropometry and circulating leptin were performed both in AIS and non-AIS girls. Evaluations of curve severity and measurements of bone mineral content/density (BMC/BMD) were performed only in AIS girls. The anthropometric data and circulating leptin levels were compared between older AIS girls and controls. The relationships between leptin and age, menstrual status, body weight, height, body mass index (BMI), Risser sign, curve magnitude, and BMC/BMD were analyzed in AIS girls. Results. Compared with healthy controls, an abnormal growth pattern (higher corrected height, lower weight, and lower BMI), and a marked decrease of circulating leptin were found in AIS girls, even after the adjustment for age and menstrual status. Positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign. No significant correlation was found between leptin and curve magnitude. There was no significant difference in age at menarche between menstruating AIS and non-AIS girls, though an inverse correlation was observed between leptin and the age at menarche. The relationship between leptin and BMC/BMD remained significantly positive after controlling for age and menstrual status, although it was not independent of body weight or BMI. Conclusion. A marked decrease of circulating leptin was observed in the current study. There was an association between leptin and body weight, BMI, other growth parameters, and BMC/BMD. This correlation suggests that leptin might play an important role in the lower body and bone mass in AIS girls.

Sagittal alignment of spine and pelvis in asymptomatic adults: norms in Chinese populations.

Study Design. A prospective, cross-sectional study. Objective. To investigate the normal values of sagittal spinal and pelvic parameters in Chinese populations and to determine the influence of age, sex, weight, and ethnicity on variations of these parameters. Summary of Background Data. A few studies have been conducted to evaluate the morphology and orientation of pelvis in asymptomatic adults of Caucasian populations. However, there is still a lack of investigation concerning the normal range of spinal and pelvic alignment in Asian populations. Methods. A cohort of 260 asymptomatic adult volunteers from Chinese Han populations was prospectively recruited. The following 6 radiological parameters on lateral radiograph were evaluated for each subject, including sacral slope (SS), pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis, and C7 tilt. Comparisons of these parameters between the male and the female and between Chinese Han populations and Caucasian populations were carried out with Student t tests. The relationships between all parameters and age and weight were assessed using the Pearson correlation analysis. Results. The mean values of spinopelvic parameters of the cohort were 44.6 ± 11.2° for pelvic incidence, 11.2 ± 7.8° for pelvic tilt, and 32.5 ± 6.5° for SS, respectively. With the age matched, subjects from Chinese populations were found to have significantly smaller pelvic incidence and SS than those from Caucasian populations. The females were found to have significantly higher lumbar lordosis than the males. Presenting significant but small correlations with age of both male and female adults, thoracic kyphosis and pelvic tilt tended to increase with age, whereas SS had a tendency to decrease with age. Weight was significantly correlated with thoracic kyphosis, SS, and lumbar lordosis. Conclusion. The normal values of sagittal spinal and pelvic parameters in Chinese populations could be significantly influenced by age, weight, and sex. Moreover, obvious variations of spinopelvic parameters were found between populations with different ethnicity background. Level of Evidence: N/A

The Influence of Closing-opening Wedge Osteotomy on Sagittal Balance in Thoracolumbar Kyphosis Secondary to Ankylosing Spondylitis: A Comparison With Closing Wedge Osteotomy

Study Design. A retrospective study. Objective. To compare the radiographical and clinical outcomes between closing wedge osteotomy (CWO) and closing-opening wedge osteotomy (COWO) for thoracolumbar kyphosis secondary to ankylosing spondylitis. Summary of Background Data. Several surgical techniques have been used to correct the fixed thoracolumbar kyphosis caused by ankylosing spondylitis. To date, the comparison of the outcomes between CWO and COWO has not yet been addressed. Methods. According to the association with anterior edge opening or not shown on the postoperative radiographs, 64 patients were divided into 2 groups (35 patients in the CWO group and 29 patients in the COWO group). The radiographical and clinical outcomes were compared between the 2 groups, with a mean follow-up of 36 months (range, 24–84 mo). Radiographical measurements included thoracic kyphosis, lumbar lordosis, global kyphosis, sagittal vertical axis, osteotomized vertebra angle, and the height of the osteotomized vertebra. Oswestry Disability Index was evaluated at the final follow-up. Results. Thoracic kyphosis did not change significantly between postoperatively and the final follow-up in both groups. The mean corrections of lumbar lordosis, global kyphosis, sagittal vertical axis, and osteotomized vertebra angle were significantly larger in the COWO group than in the CWO group (P < 0.05). Notably, statistically significant differences (P < 0.05) were observed in the variation of height of the osteotomized vertebra (1.3 cm in the CWO group vs. 0.7 cm in the COWO group). In both groups, no patients had pseudarthrosis at the osteotomy level at the last follow-up. There was no significant difference of Oswestry Disability Index scores between the 2 groups at the final follow-up. Conclusion. Both CWO and COWO are safe and effective surgical methods for correction of thoracolumbar kyphosis. COWO can obtain larger correction and better sagittal alignment without additional neurological complications.

Increased expression of insulin-like growth factor-1 receptor is correlated with tumor metastasis and prognosis in patients with osteosarcoma.

The aim of this study was to investigate the association of insulin‐like growth factor‐1 receptor (IGF‐1R) with metastasis and prognosis of osteosarcoma patients.

Radiological Presentations in Relation to Curve Severity in Scoliosis Associated With Syringomyelia

Background: Few radiographic guidelines are available to assist clinicians in deciding when to order magnetic resonance imaging in patients with a normal history and physical examination. Most of the recent reports on the radiographic characteristics of scoliosis are limited by a small number of patients and a shortage of large curves. The association between radiological features and the severity of scoliosis has little been elaborated. The purpose of this study is to further explore the radiological presentations in relation to curve severity in scoliosis associated with Chiari malformation and syringomyelia. Methods: A total of 87 children and adolescents were divided into 3 groups: group 1 (10 degrees ≤ Cobb angle ≤ 30 degrees), group 2 (30 degrees < Cobb angle ≤ 60 degrees), and group 3 (Cobb angle > 60 degrees). Curves were classified into typical and atypical patterns in the coronal plane, and the sagittal profile was measured. Cerebellar tonsillar descent or syrinx patterns in relation to curve severity and the frequency of atypical curves were also investigated. Results: The frequency of atypical curve patterns from groups 1 to 3 was 46.2%, 45.2%, and 40.7%, respectively. A total of 65.3% of patients with typical curve patterns had atypical features in all of the 3 groups. There was a significant difference of kyphotic angle among the 3 groups showing that the larger curves tended to have greater thoracic kyphosis. Both the degree of cerebellar tonsillar descent and syrinx patterns had no correlation with the curve severity or the frequency of atypical curves. Conclusions: These results show that radiographic presentations including atypical curve patterns, atypical features in typical curve patterns, and a normal to hyperkyphotic thoracic spine may suggest the need for a preoperative magnetic resonance imaging. Kyphosis may be indicative of progressive scoliosis. There is no evidence to suggest that the degree of cerebellar tonsillar descent and syrinx patterns have an effect on the progress of scoliosis and the frequency of atypical curves. Level of Evidence: Systematic review 2 of Level III studies.

Radiographical predictors for postoperative sagittal imbalance in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis after lumbar pedicle subtraction osteotomy.

Study Design. A retrospective radiographical study. Objective. To identify the radiographical predictors for sagittal imbalance in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) after 1-level lumbar pedicle subtraction osteotomy (PSO). Summary of Background Data. Few studies had correlated the preoperative sagittal parameters with postoperative sagittal alignments to determine the radiographical predictors for postoperative sagittal imbalance in patients with AS after 1-level lumbar PSO. Methods. Thirty-six patients with thoracolumbar kyphosis secondary to AS who underwent 1-level lumbar PSO were recruited with a minimal follow-up of 24 months (mean = 27.4 mo; range, 24–53 mo). Correlation analysis and subsequent stepwise multiple regression analysis were used to evaluate the correlations between preoperative parameters, including global kyphosis, local kyphosis, thoracic kyphosis, thoracolumbar Cobb angle, lumbar lordosis, pelvic incidence (PI), pelvic tilt, sacral slope, and sagittal vertical axis (SVA), as well as SVA at the last follow-up. All these patients were further divided into 2 groups according to the PI value (group A: PI >50°; group B: PI ⩽50°). The correction outcomes were compared between these 2 groups. Results. The preoperative SVA was not significantly different between group A and group B (157.6 mm vs. 124.5 mm; P> 0.05), and both groups had similar magnitudes of kyphosis corrections at the last follow-up (global kyphosis: 42.9°vs. 46.1°; local kyphosis: 42.7°vs. 40.5°; lumbar lordosis: 35.7°vs. 43.0°). However, group A patients had significantly larger SVA at the last follow-up (73.2 mm vs. 28.7 mm; P< 0.05) and a higher incidence of postoperative sagittal imbalance (77.8% vs. 25.9%; P< 0.05) than those in group B. The stepwise multiple regression analysis demonstrated that both preoperative SVA and PI were significant independent predictors of postoperative sagittal alignments, which explained 52.0% and 9.7% of the variability of SVA at the last follow-up, respectively. Conclusion. Patients with AS with either larger preoperative SVA or larger PI are more likely to experience failed sagittal realignments after 1-level lumbar PSO. For these patients, additional osteotomies may be recommended for satisfactory correction outcomes. Level of Evidence: 4

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.

The presence of a negative sacral slope in patients with ankylosing spondylitis with severe thoracolumbar kyphosis.

BACKGROUND Pelvic retroversion is one of the mechanisms for regulating sagittal balance in patients with a kyphotic deformity. This retroversion is limited by hip extension, which prevents the pelvis from becoming excessively retroverted, achieving a sacral slope of <0°. However, a negative sacral slope can be found in some patients with ankylosing spondylitis with thoracolumbar kyphosis. The purpose of this study was to analyze this finding. METHODS We performed a retrospective review of 106 consecutive Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis treated at our center from October 2005 to October 2012. Forty-one patients in whom the upper third of the femur was clearly visualized on lateral radiographs were analyzed. Seventeen had a sacral slope of <0° (group A) and twenty-four had a sacral slope of ≥0° (group B). Eight sagittal parameters were measured and compared between the two groups. Correlations among sacral slope, the femoral obliquity angle, and the other sagittal parameters were analyzed. RESULTS Mean global kyphosis, lumbar lordosis, pelvic tilt, the sagittal vertical axis, and the femoral obliquity angle were significantly larger in group A than in group B, whereas mean pelvic incidence and sacral slope were significantly smaller in group A (p < 0.05 for all). Global kyphosis, lumbar lordosis, pelvic tilt, and the sagittal vertical axis were significantly negatively associated with sacral slope but positively associated with the femoral obliquity angle, whereas pelvic incidence was significantly positively associated with sacral slope but negatively associated with the femoral obliquity angle (p < 0.05 for all). The femoral obliquity angle was significantly negatively associated with sacral slope (p < 0.05). CONCLUSIONS Negative sacral slope does exist in Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis. This appears to be caused by severe kyphosis, an initially small sacral slope, and pronounced tilting of the femoral shaft as a result of knee flexion, resulting in the pelvis becoming further retroverted.

Loss of correction in the treatment of thoracolumbar kyphosis secondary to ankylosing spondylitis: a comparison between Smith-Petersen osteotomies and pedicle subtraction osteotomy.

Study Design Retrospective comparison of database patients. Objective To evaluate the difference of loss of correction between Smith-Petersen osteotomies (SPOs) and pedicle subtraction osteotomy (PSO) in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (AS). Summary of Background Data SPOs and PSO are reported to be the 2 major techniques for correction of thoracolumbar kyphosis resulting from AS. Previous studies have tried to compare the indication, technical aspects, correction obtained, and complication rates between the aforementioned 2 techniques. However, reports addressing a comparison of loss of correction between SPOs and PSO are limited. Materials and Methods On the basis of the types of osteotomies, 50 patients were divided into 2 groups: (1) SPOs group (n=19) including 16 male and 3 female patients, with an age range from 21 to 40 years (mean 27 y). The preoperative global kyphosis (GK) ranged from 41 to 99 degrees (average 64.6±25.6 degrees); (2) PSO group (n=31) consisted of 26 male and 5 female patients, with an age range from 22 to 54 years (mean 36 y). The preoperative GK was 50 to 96 degrees (average 73.7±23.6 degrees). Radiographic parameters including sagittal vertical axis, T12-S1 lordosis, GK, and angle of fusion levels were measured. Results Both groups showed similar preoperative and postoperative thoracic kyphosis, lumbar lordosis, and sagittal vertical axis. The average GK was corrected to 25.5 degrees and 31.4 degrees in SPOs group and PSO group, respectively. All cases were followed for a minimum of 2 years. At the last follow-up, mean loss of correction in the fusion levels were 6.1 degrees in SPOs group and 1.3 degrees in PSO group, respectively. The difference was statistically significant (P=0.034). Loss of correction of >5 degrees occurred in 4 cases (21.1%) in SPOs group, and 5 cases (16.1%) in PSO group. Conclusions Both SPOs and PSO showed similar effect in correcting the thoracolumbar kyphosis secondary to AS. However, patients treated with the SPOs technique showed higher risk in loss of correction in the instrumented region.

A promoter polymorphism of neurotrophin 3 gene is associated with curve severity and bracing effectiveness in adolescent idiopathic scoliosis.

Study Design. A genetic association study to comprehensively investigate variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han population. Objective. To explore whether the NTF3 gene polymorphisms are associated with the susceptibility, curve severity, or bracing effectiveness of adolescent idiopathic scoliosis (AIS). Summary of Background Data. Scoliosis has developed in mice with NTF3 deficiency in previous studies. Increased expression of NTF3 mRNA was detected in the paravertebral muscle in AIS. Moreover, linkage study has defined a novel AIS locus on chromosome 12p while NTF3 gene is located exactly in this interval. All evidence indicates a potential role of NTF3 in the pathogenesis of AIS. As for brace treatment of AIS, continuous sensory stimulation caused by an orthosis could help awareness of body misalignment and trigger curve correction through postural reflex. While NTF3 gene is tightly associated with proprioceptive feedback mechanism to adjust postural control, we hypothesized NTF3 as a potential candidate gene associated with the bracing effectiveness. Methods. A total of 362 AIS patients and 377 age-matched healthy controls were recruited. Two single-nucleotide polymorphisms (SNPs) were selected on the basis of the Chinese data from the HapMap project, and genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism for each SNP, respectively. Case-control study and case-only study were performed to define the contribution of NTF3 gene polymorphisms to predisposition and disease severity of AIS. Another subgroup of 120 skeletally immature AIS patients who received continuous brace treatment for minimal 2 years was genotyped, and bracing effectiveness was assessed to determine its association with NTF3 gene polymorphisms. Results. The genotype and allele frequency distribution were similar between AIS and normal control for these 2 SNPs (&khgr;2 test: P > 0.05). For SNP rs11063714 in the promoter region of NTF3 gene, AIS patients with AA genotype showed significantly lower mean maximum Cobb angle than the patients with AG or GG genotypes (analysis of variance: P = 0.008). In addition, skeletally immature bracing AIS patients with AA genotype possessed significantly higher successful ratio of brace treatment compared with GG genotype (&khgr;2 test: P = 0.043). For SNP rs1805149, no significant association with predisposition or curve severity was detected. Conclusion. The NTF3 gene polymorphisms are not associated with the occurrence of AIS, but the promoter polymorphism (rs11063714) is associated with the curve severity, implicating an alleviating role of NTF3 in the curve progression of AIS. In addition, the promoter polymorphism is also associated with brace responsiveness. These findings indicated that NTF3 gene might be a disease-modifying gene of AIS.