Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1-4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non-AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid-etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone-like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC-Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy-dispersive X-ray spectroscopy analysis demonstrated a lower calcium-to-phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno-canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS.-Chen, H., Zhang, J., Wang, Y., Cheuk, K.-Y., Hung, A. L. H., Lam, T.-P., Qiu, Y., Feng, J. Q., Lee, W. Y. W., Cheng, J. C. Y. Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and ß-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active ß-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

A Genetic Predictive Model Estimating the Risk of Developing Adolescent Idiopathic Scoliosis.

BACKGROUND: Previous GWASs have revealed several susceptible variants associated with adolescent idiopathic scoliosis (AIS). Risk prediction based on these variants can potentially improve disease prognosis. We aimed to evaluate the combined effects of genetic factors on the development of AIS and to further develop a genetic predictive model. METHODS: A total of 914 AIS patients and 1441 normal controls were included in the discovery stage, which was followed by the replication stage composed of 871 patients and 1239 controls. Genotyping assay was performed to analyze 10 previously reported susceptible variants, including rs678741 of LBX1, rs241215 of AJAP1, rs13398147 of PAX3, rs16934784 of BNC2, rs2050157 of GPR126, rs2180439 of PAX1, rs4940576 of BCL2, rs7593846 of MEIS1, rs7633294 of MAGI1 and rs9810566 of TNIK. Logistic regression analysis was performed to generate a risk predictive model. The predicted risk score was calculated for each participant in the replication stage. RESULTS: The association of the 10 variants with AIS was successfully validated. The established model could explain approximately 7.9% of the overall variance. In the replication stage, patients were found to have a remarkably higher risk score as compared to the controls (44.2 ± 14.4 vs. 33.9 ± 12.5, p <0.001). There was a remarkably higher proportion of the risk score i.e. >40 in the patients than in the controls (59% vs. 28.9%, p <0.001). CONCLUSION: Risk predictive model based on the previously reported genetic variants has a remarkable discriminative power. More clinical and genetic factors need to be studied, to further improve the proba-bility to predict the onset of AIS.

CT-based study of vertebral and intravertebral rotation in right thoracic adolescent idiopathic scoliosis.

PURPOSE: To define the longitudinal rotation axis around which individual vertebrae rotate, and to establish the various extra- and intravertebral rotation patterns in thoracic adolescent idiopathic scoliosis (AIS) patients, for better understanding of the 3D development of the rotational deformity. METHODS: Seventy high-resolution CT scans from an existing database of thoracic AIS patients (Cobb angle: 46°-109°) were included to determine the vertebral axial rotation, rotation radius, intravertebral axial rotation, and local mechanical torsion for each spinal level, using previously validated image processing techniques. RESULTS: For all levels, the longitudinal rotation axis, from which the vertebrae rotate away from the midline, was localized posterior to the spine. The axis became closer to the spine at the apex: apex, r = 11.5 ± 5.1 cm versus two levels above (radius = 15.8 ± 8.5 cm; p < 0.001) and beneath (radius = 14.2 ± 8.2 cm; p < 0.001). The vertebral axial rotation, intravertebral axial rotation, and local mechanical torsion of the vertebral bodies were largest at the apex (21.9° ± 7.4°, 8.7° ± 13.5° and 3.0° ± 2.5°) and decreased toward the neutral, junctional zones (p < 0.001). CONCLUSION: In AIS, the vertebrae rotate away around an axis that is localized posterior to the spine. The distance between this axis and the spine is minimal at the apex and increases gradually to the neutral zones. The vertebral axial rotation is accompanied by smaller amounts of intravertebral rotation and local mechanical torsion, which increases toward the apical region. The altered morphology and alignment are important for a better understanding of the 3D pathoanatomical development of AIS and better therapeutic planning for bracing and surgical intervention. These slides can be retrieved under Electronic Supplementary Material.

Association between braced curve behavior by pubertal growth peak and bracing effectiveness in female idiopathic scoliosis: a longitudinal cohort study.

BACKGROUND: Pre-pubertal idiopathic scoliosis (IS) is associated with high risk of bracing ineffectiveness. Integrated multidimensional maturity assessments are useful but complex to predict the high-risk occurrence of curve progression. This study is designed to provide a simple screening method for brace effectiveness by determining whether or not the braced curve behavior at growth spurt, being defined as variations in Cobb angle velocity (AV) at peak height velocity (PHV), can be a new factor predictive of brace outcome prescribed before PHV. METHODS: This is a retrospective study of a series of 35 IS girls with simplified skeletal maturity score no more than 3 at initiation of bracing treatment and followed up through the growth spurt until brace weaning or surgery. Serial Cobb angle and maturity indicators involving height velocity, Risser sign, triradiate cartilage, simplified skeletal maturity score and distal radius and ulna classification were assessed and patients were stratified into either a positive or negative category based on a positive or negative value of AV at PHV. Comparisons were made between the positive and negative AV groups, as well as the failed and successful bracing groups, using independent sample T test and crosstab analysis. Logistic regression analysis was used to identify the predictive factors of failed brace treatment. RESULTS: Brace treatment prescribed before PHV was found to have an overall failure rate of 57.1% and a surgical rate of 45.7%. Negative AV at PHV accounting for 54.3% of the recruited patients were associated with lower brace failure rate (36.8% vs. 81.2%, p = 0.016) and surgical rate (21.1% vs. 75.0%, p = 0.002). Patients in the failed bracing group showed higher ratio of thoracic curve (80.0% vs. 26.7%,p = 0.002) and higher AV at growth peak (2.3 ± 9.1 vs. -6.5 ± 11.4°/yrs., p = 0.016). The logistic regression analysis revealed that positive AV at PHV (OR = 9.268, 95% CI = 1.279-67.137, p = 0.028) and thoracic curve type (OR = 13.391, 95% CI = 2.006-89.412, p = 0.007) were strong predictive factors of ineffective brace treatment initiated before PHV. CONCLUSIONS: Sustained curve correction following bracing despite early onset and rapid pubertal growth was strongly predictive of effective brace control of scoliosis.

Accurate prediction of height loss in adolescent idiopathic scoliosis: Cobb angle alone is insufficient.

PURPOSE: Spinal height loss due to scoliosis was mostly calculated by equations with Cobb angle as the unique independent variable in adolescent idiopathic scoliosis (AIS), with their accuracy being seriously doubted. The purpose of this study was to compare and correlate the measured loss in spinal height (ΔSHm) with the calculated loss in spinal height (ΔSHc), and to identify the key factors associated with height loss in AIS. METHODS: This retrospective study included two stages. In stage I, 277 surgically treated AIS patients were reviewed, and divided into single curve and double curve groups. The accuracy and limitation of each correction equation was testified by comparing the data sets of ΔSHc with the ΔSHm, as well as comparing the pre- and post-op spinal length for each correction equation. In stage II, 235 curves within 100 AIS patients were selected to explore the relationship between loss in vertical curve height (△CH) and Cobb angle, curve length (CL), number of vertebrae within the curve (NVC), tilt angle of each curve (α) through partial correlation analysis. RESULTS: In stage I, the △SHm averaged 3.5 cm in single curve group and 4.8 cm in double curve group. The ΔSHc was only comparable with ΔSHm using the Bjure's equation. Pre- and post-op spinal length was only comparable in Bjure's corrected group with Cobb angle <60° (p > 0.05). In stage II, the partial correlation coefficients of △CH with Cobb angle, CL, α, and NVC were 0.889, 0.493, -0.723 and -0.175 (p < 0.01), respectively. The △CH could be calculated by the following formula: △CH (mm) = 29.305 + 0.506Cobb + 0.083CL - 0.592α - 0.796NVC. CONCLUSIONS: Previous height correction equations employing Cobb angle as the unique independent variable are inaccurate. Cobb angle, curve length, curve inclination, and number of vertebrae within the curve are all strong determinants responsible for the height loss in AIS.

Rib-vertebral angle measurements predict brace treatment outcome in Risser grade 0 and premenarchal girls with adolescent idiopathic scoliosis.

PURPOSE: To investigate the predictive role of rib-vertebral angle (RVA) measurements in early adolescent idiopathic scoliosis (AIS) girls with right thoracic curve during brace treatment. METHODS: Early AIS (premenarchal and Risser 0) girls who had undergone brace treatment and had been followed regularly were recruited to this study. According to the bracing outcome, they were divided into Group A (non-progressed) and Group B (curve worsened over six degrees or indicated for surgery). RESULTS: Totally 48 girls were included. There were 30 and 18 patients in Groups A and B, respectively. Ratio of curve progression was significantly higher in patients with initial RVA difference (RVAD) ≥20° versus <20°, or convex RVA (CRVA) ≤68° versus >68°. From brace initiation to the latest follow-up, CRVA was found to be significantly higher in Group A versus Group B (P < 0.05), while RVAD was higher in Group B versus Group A (P < 0.05). Serial measurements revealed an increasing trend for RVAD (from 19 ± 10° to 29 ± 8°) yet a decreasing trend for CRVA (from 68 ± 6° to 60 ± 7°) in Group B, but both RVAD and CRVA were found to remain stable in Group A during the follow-up period. Association analyses showed that both RVAD ≥20° and CRVA ≤68° at brace initiation and at each follow-up were significantly associated with curve progression. CONCLUSIONS: The initial RVAD ≥20° and CRVA ≤68° serve as valid factors in predicting the risk of curve progression during bracing in early AIS. Constant watch on RVAD and CRVA can help to more accurately predict the effectiveness of bracing in these patients.

Halo-gravity traction combined with assisted ventilation: an effective pre-operative management for severe adult scoliosis complicated with respiratory dysfunction.

PURPOSE: To investigate the change of pulmonary function in adult scoliosis patients with respiratory dysfunction undergoing HGT combined with assisted ventilation. METHODS: 21 adult patients were retrospectively reviewed with a mean age of 26.2 years. Inclusion criteria were as follows: age over 18 years old; coronal Cobb angle greater than 100°; with respiratory failure; and duration of HGT more than 1 month. All patients underwent respiratory training. RESULTS: The Cobb angle averaged 131.21° and was reduced to 107.68° after HGT. Significantly increased mean forced vital capacity (FVC) was found after HGT (P = 0.003) with significantly improved percent-predicted values for FVC (P < 0.001). Meanwhile, significantly increased forced expiratory volume in 1 s (FEV1) was also observed (P < 0.001) with significantly improved percent-predicted values for FEV1 (P = 0.003) after HGT. CONCLUSION: The results of our study revealed that combined HGT and assisted ventilation would be beneficial to pulmonary function improvement in severe adult scoliosis cases, most of which were young adults.

Comparison of the scoliosis curve patterns and MRI syrinx cord characteristics of idiopathic syringomyelia versus Chiari I malformation.

PURPOSE: Although the more readily available MR imaging has brought about more incidental findings of idiopathic syringomyelia (IS), no published study has specifically addressed the clinical and imaging features of IS-associated scoliosis. Since IS and Chiari I malformation (CMI)-type syringomyelia are hypothesized to share a common underlying developmental pathomechanism, this study aimed to investigate the scoliosis curve patterns and MRI syrinx cord characteristics of patients with IS comparing with those seen in CMI. METHODS: Sixty-one patients with scoliosis secondary to IS were identified and reviewed retrospectively. The curve pattern and specific curve features were recorded and compared with historic CMI controls. Location, size, and morphological appearance of the syrinx were systematically assessed on MR images. RESULTS: The maximal syrinx/cord ratio and rostrocaudal length of the syrinx in IS averaged 0.43 ± 0.16 (range 0.17-0.78) and 4.6 ± 2.5 (range 2-15) vertebral levels, respectively, both of which were smaller than those reported in CMI-type syringomyelia. Regarding the characteristics of IS-related scoliosis, sagittal profiles as well as the frequency of curve patterns and atypical features were all found to resemble those in patients with CMI (P > .05). Among the 47 individuals with a single thoracic curve, Fisher exact test revealed a significant correlation between curve convexity and the dominant side of deviated syrinx (83.3 % concordance rate, P = .021). In addition, apex of the thoracic curve trended toward being significantly correlated with the level of maximum expansion of the syrinx (P = .066). CONCLUSIONS: Radiological characteristics of scoliosis were found to be similar between idiopathic and CMI-type syrinx in both the coronal and sagittal planes, adding further evidence to the concept that these entities may be part of a spectrum of disease sharing a common pathophysiological mechanism. The thoracic spine in IS patients tended to be convex to the deviated side of syrinx, which indirectly supported the likely role of spinal cord dysfunction in the pathogenesis of syrinx-associated spinal deformities.

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

BACKGROUND: Height 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. METHODS: Pre-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). RESULTS: Sixty-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). CONCLUSIONS: Variations 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.

Effect of upright position on tonsillar level in adolescent idiopathic scoliosis.

PURPOSE: The aim of this study was to investigate the effect of an upright position on cerebellar tonsillar level in patients with adolescent idiopathic scoliosis (AIS). METHODS: Twenty-five patients with clinically diagnosed AIS and 18 normal controls were examined in both supine and upright positions using 0.25T MRI. The position of the inferior cerebellar tonsil tip relative to a reference line connecting the basion to the opisthion (BO line) was measured in millimetres. RESULTS: None of the 18 normal control subjects had cerebellar tonsillar descent below the BO line in either supine or the upright position. Forty-eight percent of AIS patients had tonsillar descent in the upright position, compared to 28 % in the supine position. In the upright position, cerebellar tonsillar position was lower in AIS patients than in normal subjects (mean -0.7 ± 1.5 vs. +2.1 ± 1.7, p < 0.00001). AIS patients also had a large degree of tonsillar excursion between upright and supine positions compared to normal subjects (mean -1.9 ± 2.3 vs. -0.1 ± 0.2, p < 0.00001). CONCLUSIONS: When considering the theoretical likelihood that a low tonsillar position may affect spinal cord function, one should bear in mind that tonsillar descent in AIS is significantly greater in the upright position. KEY POINTS: • AIS patients exhibited greater cerebellar tonsillar descent in upright than supine position. • Cerebellar tonsillar position was lower in AIS patients than normal subjects. • AIS patients exhibited greater tonsillar excursion between supine and upright positions.

Brace treatment versus observation alone for scoliosis associated with Chiari I malformation following posterior fossa decompression: a cohort study of 54 patients.

PURPOSE: To be deemed effective in preventing curve progression, brace treatment should show alteration of the expected natural history. Most of the reported studies on the effect of bracing on the evolution of Chiari malformation-associated scoliosis (CMS) following posterior fossa decompression (PFD) were small series with inconclusive results. The goal of this study was to investigate whether post-PFD brace treatment for CMS produces better outcomes than observation alone. METHODS: The clinical and radiographic data of 21 patients treated with observation alone (Ob group) and 33 patients receiving brace treatment (Br group) were retrospectively reviewed. Evolution of scoliosis was defined as progression of Cobb angle of the primary curve of >5°, as compared with that at brace initiation. RESULTS: At the latest follow-up, curve progression occurred in 10 (30 %) of Br group and 13 (62 %) of Ob group (P = .022). Overall, 8 (24 %) patients in the Br group and 9 (43 %) in the Ob group underwent further scoliosis surgery (P = .151). When analyses were restricted to the 27 braced and 17 observed patients who had reached skeletal maturity or undergone spinal fusion surgery, decreased curve progression and surgical rates were also observed in the Br group though not reaching statistical significance. Results of the survival analysis, however, demonstrated a significantly increased survival proportion in the Br group (0.63 versus 0.35, P = .014). CONCLUSIONS: Compared with observation alone, bracing treatment following PFD in patients with CMS was observed to reduce the rates of curve progression and scoliosis surgery. However, patients and their parents should be informed that almost a third of patients still go on to surgery.

Convex-concave and anterior-posterior spinal length discrepancies in adolescent idiopathic scoliosis with major right thoracic curves versus matched controls.

PURPOSE: The apical deformation in adolescent idiopathic scoliosis (AIS) is a combination of rotation, coronal deviation and passive anterior lengthening of the spine. In AIS surgery, posterior-concave lengthening or anterior-convex shortening can be part of the corrective maneuver, as determined by the individual surgeon's technique. The magnitude of convex-concave and anterior-posterior length discrepancies, and how this needs to be modified to restore optimal spinal harmony, remains unknown. METHODS: CT-scans of 80 pre-operative AIS patients with right convex primary thoracic curves were sex- and age-matched to 80 healthy controls. The spinal length parameters of the main thoracic curves were compared to corresponding levels in controls. Vertebral body endplates and posterior elements were semi-automatically segmented to determine the length of the concave and convex side of the anterior column and along the posterior pedicle screw entry points while taking the 3D-orientation of each individual vertebra into account. RESULTS: The main thoracic curves showed anterior lengthening with a mean anterior-posterior length discrepancy of + 3 ± 6%, compared to a kyphosis of - 6 ± 3% in controls (p < 0.01). In AIS, the convex side was 20 ± 7% longer than concave (0 ± 1% in controls; p < 0.01). The anterior and posterior concavity were 7 and 22 mm shorter, respectively, while the anterior and posterior convexity were 21 and 8 mm longer compared to the controls. CONCLUSIONS: In thoracic AIS, the concave shortening is more excessive than the convex lengthening. To restore spinal harmony, the posterior concavity should be elongated while allowing for some shortening of the posterior convexity.

Abnormal cerebral cortical thinning pattern in adolescent girls with idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a 3-D spinal deformity with uncertain etiology; abnormalities in brain development represent one of the possible explanatory concepts for its pathogenesis. The objective of this study is to investigate the brain maturation by thickness of cerebral cortex among female adolescents with and without idiopathic scoliosis. Fifty AIS patients with a typical right-thoracic curve pattern were compared with 40 age-matched healthy controls. Based on the T1-weighted magnetic resonance images, the thickness of cortical gray-matter was calculated using a well-validated surface measurement method. Focusing on adolescent participants within the age range with the frequent occurrences of AIS cases (i.e., 12 to 17 years), we observed that the cortical thickness declined significantly in almost all cortical lobes in normal subjects (Spearman correlation<-0.4; P ≤ 0.05) except temporal lobe in LH, while in AIS patients this decline was weakly correlated with age (Spearman correlation>-0.4) and largely insignificant (P ≥ 0.05). Quadratic regression results expressed the detailed difference in the age-related cortical changing pattern between the two groups. In addition, focal cortical thickness was significantly different in AIS patients compared with healthy controls in areas involved in motor and vestibular functions as well as object recognition. The findings from this study imply a different thinning pattern of the cerebral cortex during adolescence in patients with AIS; this may be primary (i.e. etiopathogenetic) or secondary (i.e. adaptation) to the development of scoliosis.

Role of high central leptin activity in a scoliosis model created in bipedal amputated mice.

Significantly lower circulating leptin level has been reported in adolescent idiopathic scoliosis (AIS) compared to healthy adolescents. It was hypothesized that leptin dysfunction might be involved in the etiopathogenesis of AIS. In this study, a scoliosis model of bipedal amputated mice with high central leptin activity was established to validate this hypothesis. Three days after bipedal amputation, the mice were randomly divided into two groups: then 8 mice were injected in the hypothalamus with lentivirus vectors which expressed leptin, whereas the remaining 8 were injected with lentivirus vectors expressing GFP (control vector). X-rays were obtained at 20th week to determine the development of spinal deformity. After that all mice were sacrificed, and blood samples were collected. Then peripheral leptin levels were measured by an ELISA kit. Comparisons for the incidence of scoliosis and the severity of the curves were performed between groups. The body weight was found to be slightly lower in the leptin-vector-treated C3H/HeJ mice when compared with control mice. Significantly higher peripheral serum leptin level was found in leptin-vector-treated mice than control mice. Scoliosis was observed in all leptin-vector-treated mice with an average Cobb angle of 28.2°, and in 4/8 of control with an average Cobb angle of 23.5°. The incidence of scoliosis was significantly higher in leptin-vector-treated mice than in control group, although no significant difference was found in terms of curve severity. The results of this study indicated that the high central leptin activity might not only increase the risk of developing a scoliosis in bipedal mice but also contribute to the progression of scoliosis. The high central leptin activity might play an important role in the etiopathogenesis of scoliosis.

The value of different Risser grading systems in determining growth maturity of girls with adolescent idiopathic scoliosis.

A grading system for ossification of the iliac apophysis (Risser sign) was developed for skeletal maturity assessment in the United States (US) then adopted with modifications in France (Fr) and other countries. Despite the same name, these systems have important differences. With the aim to analyzing the difference between US and Fr Risser grading systems in determining the growth maturity of girls with adolescent idiopathic scoliosis (AIS), Fifty-three AIS girls undergoing posterior spinal correction with autogenous bone graft were recruited. The Risser grades were recorded for the non-dominant side iliac crest apophysis according to the US and Fr grading systems. Growth activity was determined by standard histologic grades (HGs) on iliac crest cartilage. As a result, Kappa statistics showed poor agreement between two grading systems. The US system showed higher correlation with HGs compared to Fr system by Spearman correlation analysis. It was also found that growth cessation could be determined by Risser grade 5 of US system or Risser grade 4 of Fr system. Furthermore, by employing Receiver Operating Characteristic (ROC) curve analysis, it was found that the Risser grade 4-5 of US system with two years after menarche could be used in determining growth cessation with the highest sensitivity, specificity and accuracy. Hence it was concluded that the US Risser grading system was better in determining maturity of girls with AIS than Fr Risser grading system. By combining years since menarche, the accuracy of Risser grades in determining growth cessation could be enhanced, and the time of weaning from a brace could be advanced.

Analysis of body growth parameters in girls with adolescent idiopathic scoliosis: single thoracic idiopathic scoliosis versus single lumbar idiopathic scoliosis.

Abnormal pattern of growth has been reported in adolescent idiopathic scoliosis (AIS) patients. However, the sequential changes of growth in different curve types of AIS have not been properly studied. The present study aimed to investigate the body growth characteristics of girls with single thoracic idiopathic scoliosis and lumbar idiopathic scoliosis in China. 339 AIS girls and 3914 healthy girls, aged 10~17yr, were included. All AIS girls had a mean Cobb angle of 32±10° (range 15~63°). According to the locations of curves end vertebrae, AIS girls were divided into 2 subgroups: a single thoracic curve and a single lumbar curve. Body weight and standing height was measured, and body mass index (BMI) and leg length was calculated of each subject in three groups, and corrected height was computed in AIS group according to Bjure's formula. One-way ANOVA was used to determine the differences in weight, height, corrected height and BMI between AIS and healthy girls. Standing height and sitting height showed no significant difference between thoracic scoliosis and lumbar scoliosis girls. Compared to healthy girls at the same age, thoracic and lumbar AIS girls had a significantly higher corrected standing and sitting height, arm span and leg length. Thoracic AIS girls had a significantly lower body weight than healthy girls at the age of 15 yr. Yet, body weight showed no significant difference between lumbar AIS and healthy girls. The standing and sitting height between thoracic and lumbar AIS girls were similar during the pubertal period. Compared to healthy girls at the same age, thoracic and lumbar AIS girls had a significantly higher corrected standing, sitting height and leg length. In addition, thoracic AIS girls are leaner than healthy girls.

Is curve direction correlated with the side of dominant displacement of cerebellar tonsil and syrinx deviation in thoracic scoliosis secondary to Chiari malformation type I and syringomyelia?

The patho-mechanism of scoliosis in patients with syringomyelia (SM) secondary to Chiari malformation type I (CMI) remains unknown up till now. In small sample studies published recently, there was an observation that curve direction tended to be on the same side as the dominant side of tonsillar displacement or the deviated side of syrinx location. Herein, a large-sample study of patients with single thoracic scoliosis secondary to CMI and SM was performed to validate these findings. The clinical and radiographic data of patients with scoliosis secondary to SM and CMI were reviewed. And patients who met the inclusion criteria were included. Based on the imaging presentation, the asymmetry of tonsillar displacement, syrinx location and scoliosis were judged by quantitative method. Then the imaging association among asymmetrically displaced tonsil, eccentrically located syrinx and curve direction were further analyzed. Thirty-nine patients with single thoracic scoliosis secondary to CMI and SM were included. 80% subjects showed concordance between the deviated side of eccentrically located syrinx and the dominant side of asymmetrically displaced tonsil. In 86% patients with asymmetrically displaced tonsil, thoracic curve was convex to the dominant side of tonsillar displacement. In 68% of patients with eccentrically located syrinx, the convex side of thoracic curve was on the same side as the deviated side of syrinx location. Asymmetrically displaced tonsils and eccentrically located syrinx are common imaging presentations in patients with SM secondary to CMI. The thoracic scoliosis in these patients was usually convex not only to the dominant side of asymmetrically displaced tonsils, but also to the side of eccentrically located syrinx, indicating that the asymmetry of tonsillar displacement and syrinx location might be involved in the regulation of curve direction.

Mutation analysis of MESP2, HES7 and DUSP6 gene exons in patients with congenital scoliosis.

MESP2, HES7 and DUSP6 genes have been proved to be involved in the etiopathogenesis of congenital scoliosis (CS) in animal embryo studies, however, whether this association was detected in human CS patients also remains unknown. One hundred sporadic and non-syndromic CS patients and 100 age-matched normal controls were included in this study. Mutation screening of gene exons were performed by DNA sequencing. However, no mutation or new single nucleotide polymorphism was found in the exons of MESP2, HES7 and DUSP6 genes in CS patients and normal controls. MESP2, HES7 and DUSP6 genes may not be involved in the etiopathogenesis of sporadic and non-syndromic CS in Chinese Han population.

Osteocyte-specific dentin matrix protein 1 : the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing.

AIMS: There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. METHODS: A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. RESULTS: Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. CONCLUSION: The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465-476.