Assessment of malalignment at early stage in adolescent idiopathic scoliosis: a longitudinal cohort study.

INTRODUCTION: Our objective was to assess abnormalities of the odontoid-hip axis (OD-HA) angle in a mild scoliotic population to determine whether screening for malalignment would help predict the distinction between progressive and stable adolescent idiopathic scoliosis (AIS) at early stage. MATERIALS AND METHODS: All patients (non-scoliotic and AIS) underwent a biplanar X-ray between 2013 and 2020. In AIS, inclusion criteria were Cobb angle between 10° and 25°; Risser sign lower than 3; age higher than 10 years; and no previous treatment. A 3D spine reconstruction was performed, and the OD-HA was computed automatically. A reference corridor for OD-HA values in non-scoliotic subjects was calculated as the range [5th-95th percentiles]. A severity index, helping to distinguish stable and progressive AIS, was calculated and weighted according to the OD-HA value. RESULTS: Eighty-three non-scoliotic and 205 AIS were included. The mean coronal and sagittal OD-HA angles in the non-scoliotic group were 0.2° and -2.5°, whereas in AIS values were 0.3° and -0.8°, respectively. For coronal and sagittal OD-HA, 27.5% and 26.8% of AIS were outside the reference corridor compared with 10.8% in non-scoliotic (OR = 3.1 and 3). Adding to the severity index a weighting factor based on coronal OD-HA, for thoracic scoliosis, improved the positive predictive value by 9% and the specificity by 13%. CONCLUSION: Analysis of OD-HA suggests that AIS patients are almost three times more likely to have malalignment compared with a non-scoliotic population. Furthermore, analysis of coronal OD-HA is promising to help the clinician distinguish between stable and progressive thoracic scoliosis.

Morphological changes of Intervertebral Disc detectable by T2-weighted MRI and its correlation with curve severity in Adolescent Idiopathic Scoliosis.

BACKGROUND: Our previous studies found disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves in adolescent idiopathic scoliosis (AIS) patients. Subsequent studies showed wedging of vertebral bodies (VB) had less contribution than intervertebral discs (IVD) to the anterior-posterior vertebral column length discrepancy in severe-AIS. However, the exact morphological changes of IVD were not clearly defined. This study aimed to evaluate the morphological and pathological changes of IVD and VB in AIS girls and healthy female controls. METHODS: This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were also evaluated on volumetric images. One-way ANOVA with Bonferroni correction and Pearson correlation tests were used. RESULTS: There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. In addition, Cobb angle was significantly correlated with wedge angle and height ratio, and inversely correlated with the volume of NP. CONCLUSIONS: In addition to wedging of VB and IVD, there was significantly reduced volume of IVD and NP in AIS patients with severe curve, insinuating the mechanical effect of scoliosis leads to a compression on both IVD and NP before significant disc desiccation occurs. We postulate that the compression of IVD and NP can contribute to curve progression in severe-AIS, these patients are more prone to disc degeneration in adulthood if no operative treatment is offered. Further longitudinal study on these parameters is still warranted.

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

Effect of curve location on the severity index for adolescent idiopathic scoliosis: a longitudinal cohort study.

OBJECTIVES: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children. A severity index was recently proposed to identify the stable from the progressive scoliosis at the first standardized biplanar radiographic exam. The aim of this work was to extend the validation of the severity index and to determine if curve location influences its predictive capabilities. METHODS: AIS patients with Cobb angle between 10° and 25°, Risser 0-2, and no previous treatment were included. They underwent standing biplanar radiography and 3D reconstruction of the spine and pelvis, which allowed to calculate their severity index. Patients were grouped by curve location (thoracic, thoracolumbar, lumbar). Patients were followed up until skeletal maturity (Risser ≥ 3) or brace prescription. Their outcome was compared to the prediction made by the severity index. RESULTS: In total, 205 AIS patients were included; 82% of them (155/189, 95% confidence interval [74-90%]) were correctly classified by the index, while 16 patients were unclassified. Positive predictive ratio was 78% and negative predictive ratio was 86%. Specificity (78%) was not significantly affected by curve location, while patients with thoracic and lumbar curves showed higher sensitivity (≥ 89%) than those with thoracolumbar curves (74%). CONCLUSIONS: In this multicentric cohort of 205 patients, the severity index was used to predict the risk of progression from mild to moderate scoliosis, with similar results of typical major curve types. This index represents a novel tool to aid the clinician and the patient in the modulation of the follow-up and, for progressive patients, their decision for brace treatment. KEY POINTS: • The severity index of adolescent idiopathic scoliosis has the potential to detect patients with progressive scoliosis as early as the first exam. • Out of 205 patients, 82% were correctly classified as either stable or progressive by the severity index. • The location of the main curve had small effect on the predictive capability of the index.

Global sagittal alignment of the spine, pelvis, lower limb after vertebral compression fracture and its effect on quality of life.

BACKGROUND: Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters. METHODS: A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires. RESULTS: Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4o ± 16.4o vs 28.4o ± 11.4o; p < 0.01), PT (25.4o ± 10.5o vs 16.6o ± 8.9o; p < 0.001), PI (54.6o ± 11.8o vs 45.8o ± 12.0o; p < 0.001), SVA (49.1 mm ± 39.6 mm vs 31.5 mm ± 29.3 mm; p < 0.01), and TPA (28.6o ± 10.8o vs 14.8o ± 8.6o; p < 0.001). Whereas for lower limb alignment, patients with VCF showed significantly higher KA (10.1o ± 7.8o vs 6.0o ± 6.4o; p < 0.001) and AA (7.0o ± 3.9o vs 4.8o ± 3.6o; p < 0.001) than controls. The number of VCF significantly correlated with lower limb alignments (KA and AA) and global sagittal balance (TPA). VCF patients showed poorer quality of life assessment scores in terms of SF-12 (30.0 ± 8.3 vs 72.4 ± 16.9; p < 0.001), ODI (37.8 ± 24.0 vs 18.7 ± 16.6; p < 0.001) and VAS (3.8 ± 2.8 vs 1.9 ± 2.2; p < 0.001). CONCLUSION: This is the first study to illustrate the abnormal lower limb alignment exhibited in patients with VCF. Patients with VCF showed an overall worse global sagittal alignment and decreased quality of life. Poorer global sagittal alignment of VCF patients also imply worse quality of life and more severe VCF.

Accuracy on the preoperative assessment of patients with adolescent idiopathic scoliosis using biplanar low-dose stereoradiography: a comparison with computed tomography.

BACKGROUND: Although computed tomography (CT) is commonly used to diagnose the scoliotic spine in patients with adolescent idiopathic scoliosis (AIS) preoperatively, it is limited by the high radiation and prone scanning position. Recently, a new biplanar stereoradiography (EOS) was used to image the scoliotic spine in an upright posture with significantly less radiation in non-severe AIS subjects. However, its reliability to assess preoperative AIS patients remains unreported. Hence, the purpose of this study is to compare the scoliotic curvature between prone (CT) and upright positions (EOS) in preoperative AIS patients. METHODS: Thirty-three pre-operative AIS patients (mean age:18.4 ± 4.2) were recruited. EOS was used to scan the whole thoracic spine at upright position. Whereas on the same day, a conventional CT scan was used to evaluate the spine in prone position. The three-dimensional reconstruction of EOS and CT of the spine were then generated. Using previous validated techniques, multiple scoliotic parameters in both modalities were determined. The agreement between the two modalities was compared using the Bland-Altman test, whereas the correlation was assessed by the intraclass correlation coefficient (ICC). RESULTS: The mean ICC (prone and upright) of intra-rater/inter-rater reliabilities for the measured parameters were 0.985,0.961/0.969,0.903, respectively. Thoracic Cobb angles, intervertebral wedging and lumbar lordosis correlated significantly between upright EOS imaging radiographs (62.9 ± 9.3°,6.4 ± 2.9° and 48.8 ± 12.4°) and prone CT (47.3 ± 10.0°,5.8 ± 2.7° and 27.9 ± 11.4°; P < 0.001). The apical vertebral wedging and apical intervertebral disc wedging showed a good correlation among the two modalities (upright, 6.5 ± 3.5° and 6.4 ± 2.9°; prone, 6.5 ± 3.6° and 5.8 ± 2.7°; R2 ≥ 0.94; P < 0.01). Similarly, there was significant correlation in apical intervertebral rotation (R2 = 0.834; P < 0.01) between the prone CT (3.4 ± 3.0°) and upright EOS (3.8 ± 3.2°). In addition, the Cobb angle was significantly larger in upright EOS (62.9 ± 9.3°) than in prone CT (47.3 ± 10.0°, P < 0.01) position. There was significant underestimation on scoliotic severity in the prone position when compared with upright position. CONCLUSIONS: Importantly, the image acquisition and reconstruction from EOS can better provide accurate three-dimensional spinal representations of the scoliotic curvature in preoperative AIS patients. Moreover, our findings suggested that scoliotic curvatures in preoperative AIS patients can be largely represented by both imaging modalities despite the difference in body positioning.

Genetic variant of BNC2 gene is functionally associated with adolescent idiopathic scoliosis in Chinese population.

Adolescent idiopathic scoliosis (AIS) is a structural curvature of the spine that was estimated to affect millions of children worldwide. Recent study shows that the functional variant rs10738445 could add to the risk of AIS through the regulation of BNC2 gene. This study aims to investigate whether the rs10738445 of BNC2 gene is a functional susceptible locus for AIS in the Chinese population and to further clarify the association of the BNC2 expression with the curve severity. SNP rs10738445 was genotyped in 1952 patients and 2492 controls, and further replicated in 693 patients and 254 controls. We found that patients have a significantly higher frequency of CC than the controls (21.9 vs. 17.7%, p = 0.004 for stage 1; 12.6 vs. 7.9%, p = 0.03 for stage 2). Allele C can significantly add to the risk of AIS with an OR of 1.14-1.24. AIS patients were found to have significantly higher BNC2 expression than the controls. The BNC2 expression was significantly correlated with the curve severity (r = 0.316, p = 0.02). In conclusion, our study suggests a functional role of BNC2 in the development and progression of the spinal deformity in AIS.

Defining the bone morphometry, micro-architecture and volumetric density profile in osteopenic vs non-osteopenic adolescent idiopathic scoliosis.

PURPOSE: Osteopenia has been widely reported in about 30 % of girls with adolescent idiopathic scoliosis (AIS). However, the bone quality profile of the 70 % non-osteopenic AIS defined by areal bone mineral density (BMD) with conventional dual-energy X-ray absorptiometry (DXA) has not been adequately studied. Our purpose was to verify whether abnormal volumetric BMD (vBMD) and bone structure (morphometry and micro-architecture) also existed in the non-osteopenic AIS when compared with matched controls using both DXA and high-resolution peripheral computed tomography (HR-pQCT). METHODS: This was a case-control cross-sectional study. 257 AIS girls with a mean age of 12.7 (SD = 0.8) years old and 187 age- and gender-matched normal controls with an average age of 12.9 (SD = 0.5) years old were included. Areal BMD (aBMD) and bone quality were measured with standard DXA and HR-pQCT, respectively. The parameters of HR-pQCT could be categorized as bone morphometry, vBMD and bone micro-architecture. The results were compared between the osteopenic AIS and osteopenic control, and between the non-osteopenic AIS and non-osteopenic control. RESULTS: In addition to the lower aBMD and vBMD, osteopenic AIS showed significantly greater cortical perimeter and trabecular area than the osteopenic control even after adjustments of age (P < 0.05). Non-osteopenic AIS also showed significantly lower aBMD together with lower cortical area, thickness and vBMD than the non-osteopenic control (P < 0.05). After adjustments of age, cortical area and vBMD, and trabecular number and separation continued to show statistical significance (P < 0.05). Both the osteopenic and non-osteopenic AIS subgroups revealed significant abnormal bone quality parameters from that in the control group after adjustments of age and aBMD with multi-linear regression analysis (P < 0.05). CONCLUSIONS: The present study specifically defined the abnormal profile of bone quality in the osteopenic and non-osteopenic AIS for the first time. Both the osteopenic and non-osteopenic AIS were likely to have relatively lower bone mineral status and abnormal bone morphometry, micro-architecture and volumetric density profile compared with their normal matched controls. The observed abnormalities were suggestive of decreased endocortical bone apposition or active endocortical resorption that could affect the mechanical bone strength in AIS. The underlying pathomechanism might be attributed to abnormal bone modeling/remodeling that could be associated with the etiopathogenesis of AIS.

Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) causes spinal deformity in 3% of children. Despite a strong genetic basis, few genes have been associated with AIS and the pathogenesis remains poorly understood. In a genome-wide rare variant burden analysis using exome sequence data, we identified fibrillin-1 (FBN1) as the most significantly associated gene with AIS. Based on these results, FBN1 and a related gene, fibrillin-2 (FBN2), were sequenced in a total of 852 AIS cases and 669 controls. In individuals of European ancestry, rare variants in FBN1 and FBN2 were enriched in severely affected AIS cases (7.6%) compared with in-house controls (2.4%) (OR = 3.5, P = 5.46 × 10(-4)) and Exome Sequencing Project controls (2.3%) (OR = 3.5, P = 1.48 × 10(-6)). Scoliosis severity in AIS cases was associated with FBN1 and FBN2 rare variants (P = 0.0012) and replicated in an independent Han Chinese cohort (P = 0.0376), suggesting that rare variants may be useful as predictors of curve progression. Clinical evaluations revealed that the majority of AIS cases with rare FBN1 variants do not meet diagnostic criteria for Marfan syndrome, though variants are associated with tall stature (P = 0.0035) and upregulation of the transforming growth factor beta pathway. Overall, these results expand our definition of fibrillin-related disorders to include AIS and open up new strategies for diagnosing and treating severe AIS.

A Critical Comparison Between Two Scanning Protocols of High-Resolution Peripheral Quantitative Computed Tomography at the Distal Radius in Adolescents.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a unique technology for assessing bone mineral density and bone microarchitecture. Currently, no universally accepted protocol for selecting the region of interest (ROI) at the distal radius has been established for growing subjects. This study aimed (1) to investigate the differences in HR-pQCT measurements of 2 different ROI protocols applied to the distal radius of healthy adolescents and (2) to identify the least common area of ROI (the least common ROI) between the protocols. Twenty-six boys and 26 girls aged between 13 and 16 yr old were recruited. Nondominant distal radius was scanned by 2 HR-pQCT protocols, namely, the "5-mm protocol," where the distal end of ROI started at 5 mm proximal to a reference line, and the "4% protocol," where the ROI started at 4% of the ulnar length proximal to another reference line. The least common ROI between the 2 protocols was identified and the slice numbering within the common ROI was determined. Bland-Altman plots were used to check the agreement of the least common ROIs between the 2 protocols. Paired t-test and Wilcoxon signed-rank test were used for analysis. In boys, significant differences between protocols were found in most parameters with the maximum difference observed in the cortical area (25.0%, p < 0.001). In girls, differences were observed only for total volumetric bone mineral density (3.6%, p = 0.032). The number of slices in the least common ROI was 66 (60.0%) and 57 (51.8%) in boys and girls, respectively. Good agreements on all HR-pQCT parameters from the least common ROI between the 2 protocols were found. Significant differences in bone parameters were noted between the 2 protocols. When comparing the 2 protocols, observed gender differences could reflect the differences in skeletal growth at the peripubertal period between genders. Least common ROI could be useful for cross-center comparisons and when merging datasets from different centers.

A validation study on the traditional Chinese version of Spinal Appearance Questionnaire for adolescent idiopathic scoliosis.

PURPOSE: "Simplified Chinese" version of Spinal Appearance Questionnaire (SC-SAQ) for patients with adolescent idiopathic scoliosis (AIS) was available but did not fit for communities using "Traditional Chinese" as their primary language. We developed a traditional Chinese version of SAQ (TC-SAQ) and evaluated its reliability and validity. METHODS: TC-SAQ was administered to 112 AIS patients, of which 101 bilingual (English and Chinese) patients completed E-SAQ and the traditional Chinese version of Scoliosis Research Society-22 questionnaire (TC-SRS-22). Internal consistency and test-retest reliability were evaluated. Concurrent validity was evaluated by comparing TC-SAQ score with E-SAQ score, and convergent validity by comparing TC-SAQ score with TC-SRS-22 self-image domain score, and discriminant validity by analyzing the relationship between TC-SAQ score and patients' characteristics. RESULTS: Internal consistency of individual TC-SAQ domain was high (Cronbach's α = 0.785 to 0.940), except for general (Cronbach's α = 0.665) and shoulders (Cronbach's α = 0.421) domain. Test-retest reliability of TC-SAQ was good (ICCs of each domain from 0.798 to 0.865). Concurrent validity demonstrated an excellent correlation between TC-SAQ and E-SAQ scores (r = 0.820 to 0.954, P < 0.0001 for all domains). Correlation between TC-SAQ domains and TC-SRS-22 self-image domain was weak to moderate. TC-SAQ total score and individual domain scores (except waist and chest domains) were positively correlated to major curve magnitude. CONCLUSIONS: TC-SAQ had good internal consistency and test-retest reliability. Concurrent validity evaluated against the original English version was excellent. TC-SAQ was both reliable and valid for clinical use for AIS patients using traditional Chinese as their primary language.

Initial Cobb angle reduction velocity following bracing as a new predictor for curve progression in adolescent idiopathic scoliosis.

PURPOSE: The initial correction rate (ICR) has been widely used as a predictor for curve progression in adolescent idiopathic scoliosis (AIS) undergoing bracing treatment. We proposed a new parameter, the initial Cobb angle reduction velocity (ARV), for prediction of curve progression. The purpose of this study was to identify whether the initial ARV was a more effective predictor than ICR for curve progression in AIS patients undergoing brace treatment, and to evaluate the ideal cut-off point of initial ARV for prediction of curve progression. METHODS: This was a retrospective cohort study on AIS girls receiving standardized bracing treatment regularly followed up every 3-6 months. Standardized SRS criteria for bracing study were utilized in the case selection. The demographic data, maturity status and Cobb angle of each visit were recorded. The initial ARV and ICR were identified. Patients were divided into progressive (≥6°) and non-progressive (<6°) groups based on their final bracing outcome. Differences between two groups were identified and logistic regression analysis was applied to compare the predictive values of initial ARV and ICR for curve progression during bracing treatment. RESULTS: Seventy-six patients were included in the non-progressive group and 19 in the progressive group. Significant differences between non-progressive and progressive groups were found in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). The logistic regression analysis revealed that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had higher predictive values than ICR (P = 0.601) for curve progression in braced AIS girls. The ideal cut-off point of initial ARV was 10°/year (OR 8.959, P = 0.005) for the prediction of curve progression. CONCLUSIONS: The initial Cobb angle reduction velocity serves as a better predictor for curve progression than initial correction rate in braced AIS patients with follow-up interval of 3-6 months. At the second visit following bracing prescription, those AIS patients with reduction velocity in Cobb angle lower than 10°/year have significantly higher risk of curve progression.

Are there gender differences in sagittal spinal pelvic inclination before and after the adolescent pubertal growth spurt?

PURPOSE: Significant progression of spinal deformity could occur during the peak of pubertal growth in adolescent idiopathic scoliosis (AIS). Gender differences in spinal and vertebral inclination have been reported in asymptomatic young adults and are thought to affect the risk of curve progression in male and female AIS. The present study aimed to investigate whether there were gender differences in the sagittal spinal-pelvic profile and whether any differences occurred before or developed during the normal pubertal growth spurt. METHODS: The sagittal up-right standing spine X-ray films from 71 male and 82 female asymptomatic adolescents were collected. The inclination of the global spine was analyzed by measuring the spino-sacral angle (SSA) and the spinal tilt (ST). Additionally, the inclination of the vertebrae (T1-L5), thoracic kyphosis (T4-T12) and lumbar lordosis were measured. These subjects were divided into the ascending phase (non-fused triradiate cartilage) G1 subgroup, the peak (fused triradiate cartilage and Risser grade 0-1) G2 subgroup and the late phase (Risser grade 2-5) of pubertal growth G3 subgroup. The comparisons between the males and females were carried out within the subgroups. RESULTS: In the subgroups G1 and G2, the females showed a trend of less ventral inclination in the upper thoracic vertebrae (T1-T5) and greater dorsal inclination in the lower thoracic vertebrae (T7-T12), although the differences were not statistically significant. In the G3 subgroup, the females showed significantly larger SSA (133.7° ± 4.5° vs. 128.4° ± 4.0°), ST (96.3° ± 2.6° vs. 94.8° ± 3.4°) and dorsal inclination of T1 and T12-L2 than did the males (p < 0.05). CONCLUSIONS: Although a trend toward a more backward inclination of the spine and individual vertebrae might pre-exist during the ascending phase or peak of pubertal growth, the differences become more significant during the late stage of puberty. The observation could be related to relatively active anterior vertebral overgrowth that occurs in females during pubertal growth.

Correction: wai, m.g.C., et Al. A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis. Int. J. Mol. Sci. 2014, 15, 16484-16499.

The authors wish to make the following corrections to this paper [1]: The first name and surname of the authors were reversed. It should be corrected in the following format (with the surname in bold text):[...].

A prospective randomized controlled study on the treatment outcome of SpineCor brace versus rigid brace for adolescent idiopathic scoliosis with follow-up according to the SRS standardized criteria.

PURPOSE: SpineCor is a relatively innovative brace for non-operative treatment of adolescent idiopathic scoliosis (AIS). However, the effectiveness of SpineCor still remains controversial. The objective of the current study was to compare the treatment outcomes of SpineCor brace with that of rigid brace following the standardized Scoliosis Research Society (SRS) criteria on AIS brace study. METHODS: Females subjects with AIS and aged 10-14 were randomly allocated into two groups undergoing treatment of SpineCor (S Group, n = 20) or rigid brace (R Group, n = 18). During SpineCor treatment, patients who had curve progression of >5° would be required to switch to rigid brace treatment. The effectiveness of the two brace treatments was assessed using the SRS standardized criteria. RESULTS: Before skeletal maturity, 7 (35.0%) patients in the S Group and 1 (5.6%) patient in the R Group had curve progression >5° (P = 0.026). At skeletal maturity, 5 of the 7 (71.4%) patients who failed with SpineCor bracing showed control from further progression by changing to rigid bracing. At the latest follow-up with a mean duration of 45.1 months after skeletally maturity, 29.4% of patients who were successfully treated by rigid brace showed further curve progression beyond skeletal maturity, versus 38.5% of patients in the SpineCor group (P > 0.05). For both groups, the primary curves were slightly improved at the time of brace weaning, but additionally increased at the latest follow-up, with a rate of 1.5° per year for post-maturity progression. CONCLUSIONS: Curve progression rate was found to be significantly higher in the SpineCor group when compared with the rigid brace group. Changing to rigid bracing could control further curve progression for majority of patients who previously failed with SpineCor bracing. For both SpineCor and rigid brace treatments, 30-40% of patients who were originally successfully treated by bracing would exhibit further curve progression beyond skeletal maturity. The post-maturity progression rate was found to be 1.5° per year in the current study, which was relatively greater than those reported before.

Abnormal response of the proliferation and differentiation of growth plate chondrocytes to melatonin in adolescent idiopathic scoliosis.

Abnormalities in the melatonin signaling pathway and the involvement of melatonin receptor MT2 have been reported in patients with adolescent idiopathic scoliosis (AIS). Whether these abnormalities were involved in the systemic abnormal skeletal growth in AIS during the peripubertal period remain unknown. In this cross-sectional case-control study, growth plate chondrocytes (GPCs) were cultured from twenty AIS and ten normal control subjects. Although the MT2 receptor was identified in GPCs from both AIS and controls, its mRNA expression was significantly lower in AIS patients than the controls. GPCs were cultured in the presence of either the vehicle or various concentrations of melatonin, with or without the selective MT2 melatonin receptor antagonist 4-P-PDOT (10 µM). Then the cell viability and the mRNA expression of collagen type X (COLX) and alkaline phosphatase (ALP) were assessed by MTT and qPCR, respectively. In the control GPCs, melatonin at the concentrations of 1, 100 nM and 10 µM significantly reduced the population of viable cells, and the mRNA level of COLX and ALP compared to the vehicle. Similar changes were not observed in the presence of 4-P-PDOT. Further, neither proliferation nor differentiation of GPCs from AIS patients was affected by the melatonin treatment. These findings support the presence of a functional abnormality of the melatonin signaling pathway in AIS GPCs, which might be associated with the abnormal endochondral ossification in AIS patients.

Distinguishing risk of curve progression in adolescent idiopathic scoliosis with bone microarchitecture phenotyping - a 6-year longitudinal study.

Low bone mineral density and impaired bone qualities have been shown to be important prognostic factors for curve progression in Adolescent Idiopathic Scoliosis (AIS). There is no evidence-based integrative interpretation method to analyse high-resolution peripheral quantitative computed tomography (HR-pQCT) data in AIS. This study aimed to (a) utilize unsupervised machine learning to cluster bone microarchitecture phenotypes on HR-pQCT parameters in AIS girls, (b) assess the phenotypes' risk of curve progression and progression to surgical threshold at skeletal maturity (primary cohort), and (c) investigate risk of curve progression in a separate cohort of mild AIS girls whose curve severity did not reach bracing threshold at recruitment (secondary cohort). Patients were followed up prospectively for 6.22 ± 0.33 years in the primary cohort (N = 101). Three bone microarchitecture phenotypes were clustered by Fuzzy C-Means at time of peripubertal peak height velocity (PHV). Phenotype-1 had normal bone characteristics. Phenotype-2 was characterized by low bone volume and high cortical bone density, and Phenotype-3 had low cortical and trabecular bone density and impaired trabecular microarchitecture. The difference in bone qualities amongst the phenotypes was significant at peripubertal PHV and continued to skeletal maturity. Phenotype-3 had significantly increased risk of curve progression to surgical threshold at skeletal maturity (Odd Ratios (OR) = 4.88; 95% Confidence Interval (CI): 1.03-28.63). In the secondary cohort (N = 106), both Phenotype-2 (adjusted OR = 5.39; 95%CI: 1.47-22.76) and Phenotype-3 (adjusted OR = 3.67; 95%CI: 1.05-14.29) had increased risk of curve progression ≥6° with mean follow-up of 3.03 ± 0.16 years. In conclusion, three distinct bone microarchitecture phenotypes could be clustered by unsupervised machine learning on HR-pQCT generated bone parameters at peripubertal PHV in AIS. The bone qualities reflected by these phenotypes were found to have significant differentiating risk of curve progression and progression to surgical threshold at skeletal maturity in AIS.

Adolescent Idiopathic Scoliosis (AIS) is an abnormal spinal curvature commonly presents during puberty growth. Evidence has shown that low bone mineral density and impaired bone qualities are important risk factors for curve progression in AIS. High-resolution peripheral quantitative computed tomography (HR-pQCT) has improved our understanding of bone qualities in AIS. It generates a large amount of quantitative and qualitative bone parameters from a single measurement, but the data are not easy for clinicians to interpret and analyse. This study enrolled AIS girls and used unsupervised machine learning model to analyse their HR-pQCT data at first clinic visit. The model clustered the patients into 3 bone microarchitecture phenotypes (i.e. Phenotype-1: normal, Phenotype-2: low bone volume and high cortical bone density, and Phenotype-3: low cortical and trabecular bone density and impaired trabecular microarchitecture). They were longitudinally followed up for 6 years until skeletal maturity. We observed the three phenotypes were persistent, and Phenotype-3 had a significantly increased risk of curve progression to severity that requires invasive spinal surgery (Odds Ratio = 4.88, P = 0.029). The difference in bone qualities reflected by these 3 distinct phenotypes could aid clinicians to differentiate risk of curve progression and surgery at early stages of AIS.

Monitoring of Curve Progression in Patients with Adolescent Idiopathic Scoliosis Using 3-D Ultrasound.

OBJECTIVE: The aim of the work described here was to determine whether 3-D ultrasound can provide results comparable to those of conventional X-ray examination in assessing curve progression in patients with adolescent idiopathic scoliosis (AIS). METHODS: One hundred thirty-six participants with AIS (42 males and 94 females; age range: 10-18 y, mean age: 14.1 ± 1.9 y) with scoliosis of different severity (Cobb angle range: 10º- 85º, mean: of 24.3 ± 14.4º) were included. Each participant underwent biplanar low-dose X-ray EOS and 3-D ultrasound system scanning with the same posture on the same date. Participants underwent the second assessment at routine clinical follow-up. Manual measurements of scoliotic curvature on ultrasound coronal projection images and posterior-anterior radiographs were expressed as the ultrasound curve angle (UCA) and radiographic Cobb angle (RCA), respectively. RCA and UCA increments ≥5º represented a scoliosis progression detected by X-ray assessment and 3-D ultrasound assessment, respectively. RESULTS: The sensitivity and specificity of UCA measurement in detecting scoliosis progression were 0.93 and 0.90, respectively. The negative likelihood ratio of the diagnostic test for scoliosis progression by the 3-D ultrasound imaging system was 0.08. CONCLUSION: The 3-D ultrasound imaging method is a valid technique for detecting coronal curve progression as compared with conventional radiography in follow-up of AIS. Substituting conventional radiography with 3-D ultrasound is effective in reducing the radiation dose to which AIS patients are exposed during their follow-up examinations.

Clinical Outcomes of 111 Patients with Early Onset Idiopathic Scoliosis (EOIS) Receiving Brace Treatment: A Longitudinal Retrospective Cohort Study.

Introduction: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. Methods: One hundred and eleven patients with EOIS (mean age of 8.6 ± 1.25 at diagnosis) received bracing treatment and had a final follow-up beyond skeletal maturity were identified from records between 1988 and 2021. Demographic data and clinical features of spinal curvature were obtained for correlation analyses to determine the associations between curve outcomes and clinical features. Results: Most patients were female (85.6%) and had a major curve on the left side (67%). The mean baseline Cobb angle of major curves was 21.73 ± 7.92°, with a mean Cobb angle progression of 18.05 ± 19.11°. The average bracing duration was 5.3 ± 1.9 years. Only 26 (23.4%) of them underwent surgery. The final Cobb angle and curve progression at the final follow-up with a Cobb angle of ≥50° were positively correlated with the initial Cobb angle (r = 0.206 and r = 0.313, respectively) and negatively correlated with maturity parameters. The lumbar curve type was found to correlate with a smaller final Cobb angle. Conclusions: The majority of patients had a final Cobb angle < 50°, which was considered a successful bracing outcome. The final Cobb angle correlated with the initial Cobb angle and curve types observed in EOIS.