Progression Of Adolescent Idiopathic Scoliosis Research Articles

3D prediction of curve progression in adolescent idiopathic scoliosis based on biplanar radiological reconstruction.

This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis. A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included "adolescent idiopathic scoliosis","3D", and "progression". The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included. Torsion index (TI) and apical vertebral rotation (AVR) were identified as accurate predictors of curve progression in early visits. Initial TI > 3.7° and AVR > 5.8° were predictive of curve progression. Thoracic hypokyphosis was inconsistently observed in progressive curves with weak evidence. While sagittal wedging was observed in mild curves, there is insufficient evidence for its correlation with curve progression. In curves with initial Cobb angle < 25°, Cobb angle was a poor predictor for future curve progression. Prediction accuracy was improved by incorporating serial reconstructions in stepwise layers. However, a lack of post-hoc analysis was identified in studies involving geometrical models. For patients with mild curves, TI and AVR were identified as predictors of curve progression, with TI > 3.7° and AVR > 5.8° found to be important thresholds. Cobb angle acts as a poor predictor in mild curves, and more investigations are required to assess thoracic kyphosis and wedging as predictors. Cumulative reconstruction of radiographs improves prediction accuracy. Comprehensive analysis between progressive and non-progressive curves is recommended to extract meaningful thresholds for clinical prognostication.

Using Electric Stimulation of the Spinal Muscles and Electromyography during Motor Tasks for Evaluation of the Role in Development and Progression of Adolescent Idiopathic Scoliosis.

Introduction: The role of the spinal muscles in scoliogenesis is not fully substantiated. Do they act scoliogenic (inducing scoliosis) or counteract scoliosis in adolescent idiopathic scoliosis (AIS)? In this study, we will examine this by using selectively placed Transcutaneous Electric Stimulation (TES) combined with a cinematic radiographic technique and by performing electromyographic (EMG) evaluations during various motor tasks. Method: This is a cross-sectional study of subjects with small-curve AIS. Using cinematic radiography, they were evaluated dynamically either under electrical stimulation or when performing motor tasks of left and right lateral bending and rotation whilst measuring the muscle activity by EMG. Results: Forty-five patients with AIS were included as subjects. Five subjects volunteered for TES and six subjects performed the motor tasks with EMG. At the initial visual evaluation, and when stimulated with TES, the frontal plane spatial positions of the vertebral bodies showed discrete changes without an apparent pattern. However, analyzing the spatial positions when calibrated, we found that the spinal muscles exert a compressive 'response' with a minor change in the Cobb angle (CA) in small-curve AIS (CA = 10-20°). In larger curves (CA > 20°), TES induced a 'larger deformity' with a relative four-fold change in the CA compared to small-curve AIS with a ratio of 0.6. When evaluating local amplitude (peak) or cumulative (mean) EMG signals, we were unable to find consistent asymmetries. However, one subject had rapid progression and one regressed to a straight spine. When adding the absolute EMG ratios for all four motor tasks, the subject with progression had almost 10-fold less summed EMG ratios, and the subject with regression had more than 3-fold higher summed EMG ratios. Discussion: Based on these findings, we suggest that the spinal muscles in small-curve AIS have a stabilizing function maintaining a straight spine and keeping it in the midline. When deformities are larger (CA > 20°), the spine muscle curve exerts a scoliogenic 'response'. This suggests that the role of the muscles converts from counteracting AIS and stabilizing the spine to being scoliogenic for a CA of more than 20°. Moreover, we interpret higher EMG ratios as heightened asymmetric spinal muscle activity when the spinal muscles try to balance the spine to maintain or correct the deformity. When progression occurs, this is preceded or accompanied by decreased EMG ratios. These findings must be substantiated by larger studies.

Physiotherapeutic Scoliosis-Specific Exercises (PSSE-Schroth) can reduce the risk for progression during early growth in curves below 25°: prospective control study.

The main treatment aim in mild scoliosis is to prevent progression and if possible, to avoid bracing. Physiotherapeutic Scoliosis Specific Exercises (PSSE) are curve pattern specific exercises, based on 3D self-correction and activities of daily living training. The objective of this study was to evaluate the efficacy of PSSE - Schroth, as an exclusive treatment, during the riskiest period of rapid growth. Prospective control study. Outpatient treatment. Adolescents with scoliosis. One hundred and sixty-three patients (148 girls,15 boys; mean age 12.6 years, Risser sign 1.1, thoracic (Th) Cobb angle 20.8° and lumbar/thoracolumbar (L/TL) Cobb angle 20.7°) performed PSSE - Schroth exercises in our clinic. They were asked to regularly attend supervised sessions and to follow a home-program at least 5 times per week. Our inclusion criteria were Cobb angle 15°-25°, Risser 0-2 and angle trunk rotation (ATR) >5°, measured by scoliometer. The outcome parameters were the Cobb angle before and after the intervention (improvement or progression were defined as angle difference more than 5°) and the number of patients that finally needed a brace. Average follow-up time was 29.4 months. Control group was consisted of 58 patients (54 girls, 4 boys; mean age 13.1 years, Risser sign 0-2, Th Cobb 19.4°, L/TL Cobb 19.2°), that were retrospectively analyzed and performed general or no exercises. Compliance was self-reported. Statistical analysis was performed by paired t-test. For PSSE - Schroth group, 103 patients (63.2%) remained stable, 39 (23.9%) improved and 21 (12.9%) worsened. The success rate (87.1%) was significantly higher compared to Control group (P=0.002), where 15 subjects (25.9%) were stable and 43 (74.1%) worsened. Similarly, 16 patients (9.8%) from PSSE - Schroth group finally needed a brace, while 39 (67.2%) from control group (P=0.01). PSSE - Schroth reduced the risk of progression in Adolescent Idiopathic Scoliosis (AIS) patients, during early growth. Our results are in accordance with the recently published literature, showing the effectiveness of PSSE and their superiority compared to general exercises or natural history. Scoliosis specific exercises can be the first step of scoliosis treatment in mild curves, to avoid progression and bracing.

Nighttime Bracing or Exercise in Moderate-Grade Adolescent Idiopathic Scoliosis

Moderate-grade adolescent idiopathic scoliosis (AIS) may be treated with full-time bracing. For patients who reject full-time bracing, the effects of alternative, conservative interventions are unknown. To determine whether self-mediated physical activity combined with either nighttime bracing (NB) or scoliosis-specific exercise (SSE) is superior to a control of physical activity alone (PA) in preventing Cobb angle progression in moderate-grade AIS. The Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS) randomized clinical trial was conducted from January 10, 2013, through October 23, 2018, in 6 public hospitals across Sweden. Male and female children and adolescents aged 9 to 17 years with an AIS primary curve Cobb angle of 25° to 40°, apex T7 or caudal, and skeletal immaturity based on estimated remaining growth of at least 1 year were included in the study. Dates of analysis were from October 25, 2021, to January 28, 2023. Interventions included self-mediated physical activity in combination with either NB or SSE or PA (control). Patients with treatment failure were given the option to transition to a full-time brace until skeletal maturity. The primary outcome was curve progression of 6° or less (treatment success) or curve progression of more than 6° (treatment failure) seen on 2 consecutive posteroanterior standing radiographs compared with the inclusion radiograph before skeletal maturity. A secondary outcome of curve progression was the number of patients undergoing surgery up until 2 years after the primary outcome. The CONTRAIS study included 135 patients (45 in each of the 3 groups) with a mean (SD) age of 12.7 (1.4) years; 111 (82%) were female. Treatment success was seen in 34 of 45 patients (76%) in the NB group and in 24 of 45 patients (53%) in the PA group (odds ratio [OR], 2.7; 95% CI, 1.1-6.6). The number needed to treat to prevent curve progression with NB was 4.5 (95% CI, 2.4-33.5). Treatment success occurred in 26 of 45 patients (58%) in the SSE group (OR for SE vs PA, 1.2; 95% CI, 0.5-2.8). Up to 2 years after the primary outcome time point, 9 patients in each of the 3 groups underwent surgery. In this randomized clinical trial, treatment with NB prevented curve progression of more than 6° to a significantly higher extent than did PA, while SSE did not; in addition, allowing transition to full-time bracing after treatment failure resulted in similar surgical frequencies independent of initial treatment. These results suggest that NB may be an effective alternative intervention in patients rejecting full-time bracing. ClinicalTrials.gov Identifier: NCT01761305.

Is Nighttime Bracing Enough to Prevent Curve Progression of Adolescent Idiopathic Scoliosis?

Is Nighttime Bracing Enough to Prevent Curve Progression of Adolescent Idiopathic Scoliosis?

Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case-control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS. The study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle <6°). Clinical and radiological assessments were conducted on each group. Cobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p < 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011). Patients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression.

Predicting Progression in Adolescent Idiopathic Scoliosis at the First Visit by Integrating 2D Imaging and 1D Clinical Information.

Retrospective observational study. The prediction of curve progression in patients with adolescent idiopathic scoliosis (AIS) remains an unresolved area in orthopedic surgery. To make a rapid meaningful prediction, easily accessible multi-dimensional data at the patient's first consultation should be used. Current studies use clinical growth parameters and numerical values extracted from radiographs to compile a predictive model, leaving out the radiographs themselves. Such practice inevitably wastes a lot of information. Thus, this study aims to create a neural network that can predict AIS progression among patients with curves indicated for bracing by integrating both one-dimensional (1D) clinical and two-dimensional (2D) radiological data collected at the patient's first visit in a fully automated manner. 513 idiopathic scoliosis patients indicated for and managed with bracing orthosis were recruited. After exclusion, 463 patients were included in deep learning analysis. Processed first-visit growth parameters and posteroanterior radiographs are used as training inputs and the curve progression outcomes obtained in follow ups are used as binary training outputs. The CapsuleNet architecture was modified and trained accordingly to make a prediction. The final model achieved 90% sensitivity with an overall accuracy of 73.9% in the prediction of AIS in-brace curve progression by using first-visit multi-dimensional data, outperforming conventional convolutional neural networks. This first-ever multidimensional-input model shows promise in serving as a screening tool for AIS in-brace curve progression. The incorporation of such a model into routine AIS diagnostic pipeline can assist orthopedics clinicians in personalizing the most appropriate management for each patient.

Quantifying Typical Progression of Adolescent Idiopathic Scoliosis: Longitudinal Three-Dimensional MRI Measures of Disc and Vertebral Deformities.

Prospective cohort study. Detail typical three-dimensional segmental deformities and their rates of change that occur within developing adolescent idiopathic scoliosis (AIS) spines over multiple timepoints. AIS is a potentially progressive deforming condition that occurs in three-dimensions of the scoliotic spine during periods of growth. However, there remains a gap for multiple time-point segmental deformity analysis in AIS cohorts during development. Thirty-six female patients with Lenke 1 AIS curves underwent two to six sequential MRIs. Scans were reformatted to produce images in orthogonal dimensions. Wedging angles and rotatory values were measured for segmental elements within the major curve. Two-tailed, paired t-tests compared morphological differences between sequential scans. Rates of change were calculated for variables given the actual time between successive scans. Pearson correlation coefficients were determined for multi-dimensional deformity measurements. Vertebral bodies (VBs) were typically coronally convexly wedged, locally lordotic, convexly axially rotated and demonstrated evidence of local mechanical torsion. Between first and final scans, apical measures of coronal wedging and axial rotation were all greater in both vertebral and intervertebral disc (IVD) morphology than non-apical regions (all reaching differences where P<0.05). No measures of sagittal deformity demonstrated a statistically significant change between scans. Cross-planar correlations were predominantly apparent between coronal and axial planes, with sagittal plane parameters rarely correlating across dimensions. Rates of segmental deformity changes between earlier scans were characterised by coronal plane convex wedging and convexly directed axial rotation. The major locally lordotic deformity changes which did occur in the sagittal plane were static between scans. This novel investigation documented a three-dimensional characterisation of segmental elements of the growing AIS spine and reported these changes across multiple timepoints. Segmental elements are typically deformed from initial presentation and subsequent changes occur in separate orthogonal planes at unique times.

Minimal Required Resolution to Capture the 3D Shape of the Human Back-A Practical Approach.

Adolescent idiopathic scoliosis (AIS) is a prevalent musculoskeletal disorder that causes abnormal spinal deformities. The early screening of children and adolescents is crucial to identify and prevent the further progression of AIS. In clinical examinations, scoliometers are often used to noninvasively estimate the primary Cobb angle, and optical 3D scanning systems have also emerged as alternative noninvasive approaches for this purpose. The recent advances in low-cost 3D scanners have led to their use in several studies to estimate the primary Cobb angle or even internal spinal alignment. However, none of these studies demonstrate whether such a low-cost scanner satisfies the minimal requirements for capturing the relevant deformities of the human back. To practically quantify the minimal required spatial resolution and camera resolution to capture the geometry and shape of the deformities of the human back, we used multiple 3D scanning methodologies and systems. The results from an evaluation of 30 captures of AIS patients and 76 captures of healthy subjects showed that the minimal required spatial resolution is between 2 mm and 5 mm, depending on the chosen error tolerance. Therefore, a minimal camera resolution of 640 × 480 pixels is recommended for use in future studies.

Ligamentous tethering and intradiscal pressure affecting the mechanical environment of scoliotic spines.

Despite several theories have been proposed to explain the progression of Adolescent Idiopathic Scoliosis (AIS), there is no consensus on the mechanical factors that control the spinal deformities. Prominent biomechanical notions focus on the geometrical asymmetry and differential growth, however, the correlation between these phenomena remains unclear. We postulate that intradiscal pressure and its connection with the supporting ligamentous structures are the reasons behind the asymmetric growth in AIS. To investigate this hypothesis, a numerical 3D patient-specific model of a scoliotic spine is constructed to carry upper body weight. Four analyses are performed: control simulation with no ligaments followed by 3 simulations, in each, a different and stiffer set of ligaments is employed. The analyses showed that intradiscal pressure is relatively high in the spine's higher-deformity region. Moreover, the stiffness effect of the ligamentous tethering correlated directly to intradiscal pressure; the stiffer the ligaments, the higher the intradiscal pressure. Due to geometrical asymmetry, the pressure is eccentric toward the concave region of deformed vertebral units. As a result, the deformed annulus fibrosus generated uplifts in the convex side of deformed vertebral units. The eccentric pressure and the uplift are opposite in location and direction creating an imbalanced mechanical environment for the spine during growth.

Metabolic Imbalances and Bone Remodeling Agents in Adolescent Idiopathic Scoliosis: A Study in Postmenarcheal Girls.

The causes and mechanisms underlying adolescent idiopathic scoliosis (AIS) remain unclear, and the available information regarding metabolic imbalances in AIS is still insufficient. This investigation aimed to evaluate the concentrations of specific bone remodeling-related agents in postmenarcheal girls diagnosed with AIS. The study encompassed thirty-six scoliosis patients and eighteen age-matched healthy individuals assigned to the control group. The patients underwent clinical and radiological examinations to assess the degree of the spinal deformity, type of curvature, and skeletal maturity. Blood and urine samples were collected from all participants and serological markers were measured using an enzyme-linked immunosorbent assay. Our study results demonstrated that the balance of phosphate-calcium and parathormone levels seems normal in individuals with AIS. Furthermore, no statistically significant differences were observed in the content of Klotho protein, osteocalcin, osteoprotegerin, C-terminal telopeptide of type I collagen (CTX), sclerostin, and alkaline phosphatase. Nevertheless, the serum levels of vitamin D (25-OH-D) were lowered, while N-terminal propeptide of type I procollagen (PINP), and fibroblast growth factor-23 (FGF23) were increased in the AIS group, with p-values of 0.044, 0.001, and 0.022, respectively. This finding indicates the potential involvement of these factors in the progression of AIS, which necessitates further studies to uncover the fundamental mechanisms underlying idiopathic scoliosis.

Deep Learning Model to Classify and Monitor Idiopathic Scoliosis in Adolescents Using a Single Smartphone Photograph

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal disorder. Routine physical examinations by trained personnel are critical to diagnose severity and monitor curve progression in AIS. In the presence of concerning malformation, radiographs are necessary for diagnosis or follow-up, guiding further management, such as bracing correction for moderate malformation and spine surgery for severe malformation. If left unattended, progressive deterioration occurs in two-thirds of patients, leading to significant health concerns for growing children. To assess the ability of an open platform application (app) using a validated deep learning model to classify AIS severity and curve type, as well as identify progression. This diagnostic study was performed with data from radiographs and smartphone photographs of the backs of adolescent patients at spine clinics. The ScolioNets deep learning model was developed and validated in a prospective training cohort, then incorporated and tested in the AlignProCARE open platform app in 2022. Ground truths (GTs) included severity, curve type, and progression as manually annotated by 2 experienced spine specialists based on the radiographic examinations of the participants' spines. The GTs and app results were blindly compared with another 2 spine surgeons' assessments of unclothed back appearance. Data were analyzed from October 2022 to February 2023. Acquisitions of unclothed back photographs using a mobile app. Outcomes of interest were classification of AIS severity and progression. Quantitative statistical analyses were performed to assess the performance of the deep learning model in classifying the deformity as well as in distinguishing progression during 6-month follow-up. The training data set consisted of 1780 patients (1295 [72.8%] female; mean [SD] age, 14.3 [3.3] years), and the prospective testing data sets consisted of 378 patients (279 [73.8%] female; mean [SD] age, 14.3 [3.8] years) and 376 follow-ups (294 [78.2%] female; mean [SD] age, 15.6 [2.9] years). The model recommended follow-up with an area under receiver operating characteristic curve (AUC) of 0.839 (95% CI, 0.789-0.882) and considering surgery with an AUC of 0.902 (95% CI, 0.859-0.936), while showing good ability to distinguish among thoracic (AUC, 0.777 [95% CI, 0.745-0.808]), thoracolumbar or lumbar (AUC, 0.760 [95% CI, 0.727-0.791]), or mixed (AUC, 0.860 [95% CI, 0.834-0.887]) curve types. For follow-ups, the model distinguished participants with or without curve progression with an AUC of 0.757 (95% CI, 0.630-0.858). Compared with both surgeons, the model could recognize severities and curve types with a higher sensitivity (eg, sensitivity for recommending follow-up: model, 84.88% [95% CI, 75.54%-91.70%]; senior surgeon, 44.19%; junior surgeon, 62.79%) and negative predictive values (NPVs; eg, NPV for recommending follow-up: model, 89.22% [95% CI, 84.25%-93.70%]; senior surgeon, 71.76%; junior surgeon, 79.35%). For distinguishing curve progression, the sensitivity and NPV were comparable with the senior surgeons (sensitivity, 63.33% [95% CI, 43.86%-80.87%] vs 77.42%; NPV, 68.57% [95% CI, 56.78%-78.37%] vs 72.00%). The junior surgeon reported an inability to identify curve types and progression by observing the unclothed back alone. This diagnostic study of adolescent patients screened for AIS found that the deep learning app had the potential for out-of-hospital accessible and radiation-free management of children with scoliosis, with comparable performance as spine surgeons experienced in AIS management.

Does Risser stage accurately predict the risk of curve progression in patients with adolescent idiopathic scoliosis treated with night-time bracing?

Risser stage is widely used as a marker for skeletal maturity (SM) and thereby an indirect measure for the risk of progression of adolescent idiopathic scoliosis (AIS). The Scoliosis Research Society recommends bracing for Risser stages 0-2 as Risser stage 3 or above is considered low risk. Very few studies have assessed the risk of progression during bracing in Risser stages 3-4. The objective of the current study is to determine if Risser stages 3-4 provide a meaningful cutoff in terms of progression risk in patients with AIS treated with night-time bracing. AIS patients treated with night-time brace from 2005 to 2018 with a Cobb angle between 25 and 40 degrees and Risser stages 0-4 were retrospectively included. Curve progression (> 5 degrees increase) was monitored until surgery or SM. Skeletal maturity was defined as either 2years postmenarchal, no height development or closed ulnar epiphyseal plates on radiographs. One hundred and thirty-five patients were included (Risser stages 0-2: n = 86 and 3-4: n = 49). Overall, radiographic curve progression occurred in 52% while progression beyond 45 degrees was seen in 35%. The progression rate in the Risser 0-2 group was 60% and 37% in the Risser 3-4 group (p = 0.012). In multivariate logistic regression analysis, adjusted for Risser stages and age, only premenarchal status showed a statistically significant association with progression (OR: 2.68, 95%CI 1.08-6.67). Risser stage does not provide a clinically meaningful differentiation of progression risk in AIS patients treated with a night-time brace. Risk assessment should include other more reliable measures of skeletal growth potential.

Differential Regulation of POC5 by ERα in Human Normal and Scoliotic Cells.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 (POC5) was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify POC5 as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the POC5 gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant POC5A429V AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of POC5, which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the POC5 promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.

The asymmetrical ESR1 signaling in muscle progenitor cells determines the progression of adolescent idiopathic scoliosis

Adolescent Idiopathic Scoliosis (AIS) is a common pediatric skeletal disease highly occurred in females. The pathogenesis of AIS has not been fully elucidated. Here, we reveal that ESR1 (Estrogen Receptor 1) expression declines in muscle stem/progenitor cells at the concave side of AIS patients. Furthermore, ESR1 is required for muscle stem/progenitor cell differentiation and disrupted ESR1 signaling leads to differentiation defects. The imbalance of ESR1 signaling in the para-spinal muscles induces scoliosis in mice, while reactivation of ESR1 signaling at the concave side by an FDA approved drug Raloxifene alleviates the curve progression. This work reveals that the asymmetric inactivation of ESR1 signaling is one of the causes of AIS. Reactivation of ESR1 signaling in para-spinal muscle by Raloxifene at the concave side could be a new strategy to treat AIS.

Axial rotation and pain are associated with facet joint osteoarthritis in adolescent idiopathic scoliosis

Facet joints are crucial for spinal stability and develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to understand better the role of facet joint degeneration in AIS progression and pain. Cartilage and bone osteoarthritic states of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and μCT analysis, respectively. Back pain was self-reported using a numerical rating scale and expressed relative to the location on the patient's back. The scoliotic curves from our patient cohort were digitally reconstructed using biplanar radiographs and the eOS system (EOS imaging). The deformity was then reduced to three intervertebral angles (coronal, sagittal and axial) for each pair of bilateral facet joints. Statistical associations between the intervertebral angles, osteoarthritis parameters and pain intensity were performed using the Spearman method and Friedman test. Facet joint cartilage degeneration was associated with decreased subchondral bone volume and quality. Most importantly, asymmetrical, and overall degeneration of facet joints was strongly correlated to intervertebral axial rotation. Additionally, kyphotic intervertebral segments in the sagittal plane were good predictors of increased facet joint degeneration and back pain. Facet joint degeneration is associated with axial deformity, kyphotic intervertebral angle and back pain intensity in AIS. These results suggest that facet joints are important features to consider for rotational instability in AIS spines and related disease progression and perceived back pain.

Compressive stress induces spinal vertebral growth plate chondrocytes apoptosis via Piezo1.

Many clinical studies have indicated an association between biomechanical factors and the incidence and pathological progression of adolescent idiopathic scoliosis (AIS). However, at present, the research on AIS is mainly focused on the etiology, and there are few studies reporting the causes of progressive aggravation of AIS. In the present study, we aim to investigate the role of Piezo1 in compressive stress-induced mouse spinal vertebral growth plate chondrocytes apoptosis. First, a scoliosis mouse model was established, and the expression of Piezo1 as well as the degree of apoptosis were investigated. We found that the expression of Piezo1 and the degree of apoptosis were significantly higher on the concave sides than that on the convex sides of the vertebral growth plate in mice with scoliosis. Spinal vertebral growth plate chondrocytes were further isolated and treated with Yoda1 to mimic Piezo1 overload. Excess Piezo1 significantly promoted apoptosis of spinal vertebral growth plate chondrocytes. Moreover, static gas compressive stress was used to simulate the increased concave compressive stress in the process of scoliosis with or without GsMTx4, a Piezo inhibitor. It was observed that with the increase of static compressive stress, the expression of Piezo1 increased, and the chondrocytes of vertebral growth plate treated with Piezo1 inhibitor GsMTx4 weakened the above phenomena. In conclusion, our results indicated that compressive stress is strongly associated with the different degrees of apoptosis on both sides on the convex and concave sides of the vertebral growth plate in scoliosis via inducing different expressions of Piezo1. Reducing the expression of Piezo1 in the concave side of the vertebral growth plate and inhibiting the apoptosis of chondrocytes in the bilateral vertebral growth plate caused by asymmetric stress on both sides of the concave vertebral body may be a promising treatment strategy for AIS.

Does Bracing Control the Progression of Adolescent Idiopathic Scoliosis in Curves Higher Than 40°? A Systematic Review and Meta-analysis.

Routinely, adolescent idiopathic scoliosis (AIS) curves that progress beyond 40° in skeletally immature adolescents require surgery. However, some adolescents with AIS and their parents utterly refuse surgery and insist on wearing a brace. Debate continues regarding the appropriateness of bracing for AIS curves exceeding 40° in patients who have rejected surgical intervention. This systematic review and meta-analysis was conducted to review the literature on the effectiveness of bracing and its predictive factors in largermagnitude AIS curves ≥40°. This study replicated the search strategy used by the PICOS system for formulating study questions, which include consideration of the patient/population (P), intervention (I), comparison (C), outcome (O), and study design (S). The search was conducted up to January 2022 in the following bibliographic online databases only in the English language: PubMed, Google Scholar, Scopus, and Web of Science. Two assessors reviewed the articles for qualification. Eligible studies were assessed for risk of bias at the study level using the Newcastle-Ottawa Scale. The effect size across the studies was determined using standardized mean differences (Cohen's d) and 95% confidence intervals for the meta-analysis. Among the eight included moderate quality studies, evidence of potential publication bias (p <0.05) for the trials included was found in the Cobb angle outcome. Results obtained through meta-analysis indicated that the effectiveness of bracing in controlling Cobb angle progression in curves ≥40° is significantly positive. Additionally, initial curve severity, Risser stage, in-brace curve correction, curve type, and apical vertebral rotation were considered risk factors associated with brace effectiveness. This systematic review revealed that bracing could alter the normal course of AIS curves ≥40° in patients refusing posterior spinal fusion (PSF). However, the suggested course for patients refusing PSF remains unclear because of the significant heterogeneity in the risk factors associated with bracing failure.

Circulatory Adipokines and Incretins in Adolescent Idiopathic Scoliosis: A Pilot Study.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional malformation of the spine of unknown cause that develops between 10 and 18 years old and affects 2-3% of adolescents, mostly girls. It has been reported that girls with AIS have a taller stature, lower body mass index (BMI), and bone mineral density (BMD) than their peers, but the causes remain unexplained. Energy metabolism discrepancies, including alterations in adipokine and incretin circulatory levels, could influence these parameters and contribute to disease pathophysiology. This pilot study aims to compare the anthropometry, BMD, and metabolic profile of 19 AIS girls to 19 age-matched healthy controls. Collected data include participants' fasting metabolic profile, anthropometry (measurements and DXA scan), nutritional intake, and physical activity level. AIS girls (14.8 ± 1.7 years, Cobb angle 27 ± 10°), compared to controls (14.8 ± 2.1 years), were leaner (BMI-for-age z-score ± SD: -0.59 ± 0.81 vs. 0.09 ± 1.11, p = 0.016; fat percentage: 24.4 ± 5.9 vs. 29.2 ± 7.2%, p = 0.036), had lower BMD (total body without head z-score ± SD: -0.6 ± 0.83 vs. 0.23 ± 0.98, p = 0.038; femoral neck z-score: -0.54 ± 1.20 vs. 0.59 ± 1.59, p = 0.043), but their height was similar. AIS girls had higher adiponectin levels [56 (9-287) vs. 32 (7-74) μg/mL, p = 0.005] and lower leptin/adiponectin ratio [0.042 (0.005-0.320) vs. 0.258 (0.024-1.053), p = 0.005]. AIS participants with a Cobb angle superior to 25° had higher resistin levels compared to controls [98.2 (12.8-287.2) vs. 32.1 (6.6-73.8), p = 0.0013]. This pilot study suggests that adipokines are implicated in AIS development and/or progression, but more work is needed to confirm their role in the disease.

Physiotherapy Interventions for Preventing Spinal Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Review.

Adolescent idiopathic scoliosis(AIS)is an abnormal curvature of the spine that appears in late childhood or adolescence. The aim of this systematic review was to present and synthesize the most relevant therapeutic advice and evidence on the efficacy of physiotherapy exercises for preventing the growth of spinal curvature caused by adolescent idiopathic scoliosis. "Adolescent idiopathic scoliosis," "exercise," "Cobb angle," and "physiotherapy" were the sole keywords used for the published research. Using these keywords and a combination of them, electronic resources such as PubMed, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database (PEDro), Elton B. Stephens Company (EBSCO) host, and ScienceDirect (Elsevier) were searched. The search was restricted to studies that were conducted in English between 2010 and 15 January 2022 that were controlled, randomized, and non-randomized. Studies were selectedbased on their titles and abstracts, with the exception of any that did not pertain to the study's goals. The Cobb angle was the important outcome measure. For each intervention, the Cobb angle's mean change score, the difference between the final and baseline scores, was determined. Nine studies were evaluated to be of outstanding quality out of a total of 20 studies that were reviewed for eligibility. With an exercise regimen of at least seven weeks, controls on lowering the Cobb angle in patients with AIS would provide encouraging outcomes. It also shows that bracing can strengthen the Cobb angle compared to exercise in the community. However, long-term orthotic activity ultimately results in trunk resistance and muscle loss in the center of the back. The combination of techniques and treatment methods seems to have better results in treating scoliosis, particularly using exercises involving the Schroth and scientific exercise approach to scoliosis (SEAS).