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.

Upregulation of microRNA-96-5p is associated with adolescent idiopathic scoliosis and low bone mass phenotype.

Bone densitometry revealed low bone mass in patients with adolescent idiopathic scoliosis (AIS) and its prognostic potential to predict curve progression. Recent studies showed differential circulating miRNAs in AIS but their diagnostic potential and links to low bone mass have not been well-documented. The present study aimed to compare miRNA profiles in bone tissues collected from AIS and non-scoliotic subjects, and to explore if the selected miRNA candidates could be useful diagnostic biomarkers for AIS. Microarray analysis identified miR-96-5p being the most upregulated among the candidates. miR-96-5p level was measured in plasma samples from 100 AIS and 52 healthy girls. Our results showed significantly higher plasma levels of miR-96-5p in AIS girls with an area under the curve (AUC) of 0.671 for diagnostic accuracy. A model that was composed of plasma miR-96-5p and patient-specific parameters (age, body weight and years since menarche) gave rise to an improved AUC of 0.752. Ingenuity Pathway Analysis (IPA) indicated functional links between bone metabolic pathways and miR-96-5p. In conclusion, differentially expressed miRNAs in AIS bone and plasma samples represented a new source of disease biomarkers and players in AIS etiopathogenesis, which required further validation study involving AIS patients of both genders with long-term follow-up.

Biological effect of dysregulated LBX1 on adolescent idiopathic scoliosis through modulating muscle carbohydrate metabolism.

BACKGROUND CONTEXT: Abnormal energy metabolism such as lower body weight and body mass index (BMI) and less fat mass is widely reported in patients with adolescent idiopathic scoliosis (AIS) and has been implicated in deformity development. However, the underlying mechanism is largely unclear. LBX1 is one of the promising AIS predisposing genes validated by multicenter studies. PURPOSE: This study aimed to identify differentially expressed proteins (DEPs) relating to energy metabolism in AIS by using proteomic and metabolic analysis and to explore if the expression of these DEPs is associated with clinical parameters and modulated by LBX1. STUDY DESIGN: This is a cross-sectional study using clinical data and biological samples followed by basic study using a cellular model. PATIENT SAMPLE: Plasma samples were collected from Chinese girls with nonprogressive and progressive AIS (N=7 and 8, respectively) and age-matched healthy girls (N=50). Paraspinal muscle tissues were collected intraoperatively from concave and convex side of the apex of the major spinal curve in AIS (N=24) and either side from nonscoliosis patients (N=14). OUTCOME MEASURES: Radiological Cobb angle and basic anthropometric data of recruited subjects were measured. The DEPs and metabolites were compared in plasma using proteomics and metabolomics technique. The relative expression of selected genes was measured in muscles. METHODS: Plasma samples from AIS were collected at first clinical visit and were further divided into nonprogressive or progressive groups according to Cobb angle changes in 6-year follow-up. Age-matched healthy girls were recruited as control. High-performance liquid chromatography-mass spectrometry based proteomic analysis was carried out in three groups to identify DEPs and their annotated metabolic pathways. An independent cohort was used for validation by gas chromatography-mass spectrometry based metabolomic analysis. Paraspinal muscles were subjected to quantitative polymerase chain reaction (qPCR) followed by correlation analysis. Human skeletal muscle myoblast (HSMM) was used as the cellular model. RESULTS: The likelihood of aberrant galactose metabolism and glycolysis was found to be associated with AIS curve progression as evidenced by the thirteen DEPs and seven related metabolites according to proteomic and metabolomic analysis. Some of the DEPs showed significantly altered expression in AIS concave and convex sides paraspinal muscles compared with those in nonscoliosis control. Four DEPs were found significantly and negatively correlated with LBX1 in AIS convex side paraspinal muscles. Overexpressing LBX1 in HSMM cells led to increased expression of three DEPs and decreased expression of three DEPs, respectively. CONCLUSIONS: This is the first integrated proteomic and metabolomic analysis on AIS. Our findings show dysregulated galactose metabolism and glycolysis pathways in progressive group of AIS, suggesting the presence of abnormal energy metabolism at early stage of this disease, and their association with higher risk of progressing into more severe curvature. Evidence from ex vivo study with human muscle biopsies and in vitro study with human myoblast cells propose the possible effect of LBX1 on these two pathways in skeletal muscles. The present study provides new evidence of LBX1 function in AIS via modulating effect on the expression of energy metabolism related genes. This study might provide new insights into etiopathogenesis and development of novel treatment strategy targeting on abnormal body weight and BMI in patients with AIS. Additionally, the plasma proteomic and metabolomic studies suggested new candidates as biomarkers for establishing predictive model for AIS onset/progression.

Effects of a Home-Based Exercise Intervention (E-Fit) on Bone Density, Muscle Function, and Quality of Life in Girls with Adolescent Idiopathic Scoliosis (AIS): A Pilot Randomized Controlled Trial.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) patients have lower physical activity levels than normal adolescents, and there is an association with poorer bone and muscle health. This study evaluated the effects of a home-based exercise intervention (E-Fit) on bone mineral density (BMD), muscle function, and quality of life (QoL) in AIS-affected girls. METHODS: A total of 40 AIS females aged 11 to 14 years were randomly assigned to the E-Fit or control group. The E-Fit group performed modified 7-min high-intensity interval training (HIIT) 5 days per week for 6 months. Outcome measures including BMD using dual-energy X-ray absorptiometry (DXA), muscle strength and endurance tests, physical activity levels, and QoL using self-reported questionnaires were assessed at baseline and at 6-month and 12-month follow-up. RESULTS: In total, 14 patients in the E-Fit and 16 in the control group completed the study. The E-Fit group showed a marginally significant interaction effect in the whole body areal BMD at the 6- (p = 0.096) and 12-month follow-ups (p = 0.085). The left arm lean mass in the E-Fit group showed a statistically significant interaction effect between the 6- and 12-month follow-ups (p = 0.046). The E-Fit group showed improvements in physical activity participation, as measured by the Modified Baecke Questionnaire (MBQ), with a significant interaction effect in work index (p = 0.043), sport index (p = 0.050), and total score (p = 0.016) from baseline to the 12-month follow-up. Improvement on self-image were noted in E-Fit group across time. CONCLUSIONS: The present results provided some evidence to support the positive benefits of E-Fit for bone health and muscle function in AIS girls.

Using Ultrasound to Screen for Scoliosis to Reduce Unnecessary Radiographic Radiation: A Prospective Diagnostic Accuracy Study on 442 Schoolchildren.

Scoliosis screening is important for timely initiation of brace treatment to mitigate curve progression in skeletally immature children and adolescents. School scoliosis screening programs in Hong Kong follow the protocol of referring children screened positive with a scoliometer and Moiré topography for confirmatory standard radiography. Despite being highly sensitive (88%) in detecting those who require specialist referral, the screening program was found to have a false-positive rate >50%, which could lead to unnecessary X-ray radiation. Radiation-free ultrasound has been reported to be valid and reliable for quantitative assessment of curve severity in scoliosis patients. The aim of this prospective diagnostic accuracy study was to determine the accuracy of ultrasound in determining the threshold of referral that requires X-ray for children screened positive with the scoliometer and Moiré topography. Our study recruited 442 schoolchildren with a mean Cobb angle of 14.0 ± 6.6°. The sensitivity and specificity of ultrasound in predicting the correct referral status, confirmed by X-ray, were 92.3% and 51.6%, with positive and negative predictive values of 29.0% and 96.9%, respectively. Receiver operating characteristic curve analysis revealed area under the curve values of 0.735 for ultrasound alone and 0.832 for ultrasound in combination with measurement of angle of trunk rotation. The finding supports the accuracy of using ultrasound to determine referral status, which could result in a >50% reduction of unnecessary radiation for children undergoing scoliosis screening.

Changes in Health-Related Quality of Life (HRQOL) of a Specific Group of Adolescent Idiopathic Scoliosis (AIS) Patients Who Came Across Both Bracing and Surgery.

BACKGROUND/PURPOSE OF THE STUDY: Changes in health-related quality of life (HRQOL) of AIS patients coming across both bracing and surgery have not yet reported. These patients received two major clinical interventions and their HRQOL might be different from previous articles. The aim of this study is to evaluate the changes of HRQOL of a specific group of AIS patients who experienced both bracing and surgery. METHODS: One hundred and twenty-eight patients requiring surgery with prior bracing treatment were identified from the electronic record. SRS-22 questionnaire was completed at 7 time points crossing both interventions (namely "Before", "Bracing ≤ 1 year", "Bracing > 1 year", "Pre-op", "Post-op", "Post-op ≤ 1 year, and "Post-op 1-2 years"). RESULTS: SRS-22 "Function", "Pain" and "Self-image" scores were decreased from "Before" to "Bracing ≤ 1 year" when started bracing and raised at "Bracing > 1 year". The 3 scores were dropped from "Bracing > 1 year" to "Pre-op", particularly on "Self-image". "Function" and "Pain" were significantly dropped from "Pre-op" to "Post-op" and kept raising until "Post-op 1-2 years". "Self-image" was improving after "Pre-op". "Mental" was relatively stable along the timeline. CONCLUSION: This study described the changes in HRQOL of a specific group of AIS patients. Scores were dropped after the two major clinical interventions and recovered afterwards. Medical professionals were able to plan and provide appropriate supports on the expected changes in HRQOL, especially on function, pain and mental.

Global sagittal alignment after surgery of right thoracic idiopathic scoliosis in adolescents and adults with and without thoracic hypokyphosis.

This study aimed to characterize global sagittal alignment in adolescent idiopathic scoliosis (AIS) with normal kyphosis (NTK, kyphosis > 10°) and with thoracic hypokyphosis (THK, kyphosis < 10°), before and after posterior spinal fusion, and compare them with asymptomatic controls. 27 AIS girls and young adults with right thoracic curves were included (seventeen with age ≤ 18 years, then age > 21). Biplanar radiographies were acquired at baseline, immediate post-operatively, 1-year and 2-year follow-up, and 3D reconstruction of the spine and pelvis was performed. NTK and THK showed different global sagittal alignment, as well as differences compared to controls. AIS with THK at baseline had higher SVA/SFD (2.0 ± 2.9 vs - 0.4 ± 1.9; P < 0.05) and OD-HA (0.2 ± 1.4° vs - 1.3 ± 1.6°; P < 0.05) than controls, indicating that THK had compensated balance with unusual forward leaning posture. Immediately post-operation, SVA/SFD remained high (1.3 ± 3.0) while OD-HA reversed (- 1.2 ± 1.7°), indicating that THK patients had found partially compensated balance. After 2-yeas, both SVA/SFD (- 1.3 ± 2.1) and OD-HA (- 1.4 ± 0.9°) were normalized. The changes in global sagittal alignment and mechanism of balance are different in AIS with or without THK. As the head plays a critical role on balance during immediate and delayed post-operation, OD-HA can be complementary parameter for assessing global balance during post-operative follow-up of AIS patients with THK.

Health-related quality of life (HRQOL) of adolescent idiopathic scoliosis (AIS) patients from surgery to after 30 years using SRS-22 questionnaire.

STUDY DESIGN: A retrospective longitudinal follow-up study. OBJECTIVES: The aim of this study is to evaluate the health-related quality of life (HRQOL) of post-operative AIS patients from less than 1 year to over 30 years using SRS-22 questionnaire. Some of our AIS patients who operated since the establishment of the scoliosis clinic have passed the 30th year. The HRQOL of patients many years after surgery had yet to be summarized and reported. METHODS: SRS-22 questionnaire was conducted by 254 operated patients between the year 2016 and 2018. All post-operative patients who visited a specialized clinic for annual check-up within the study period completed SRS-22. The number of years since surgery per questionnaire was grouped per 1 year until the 10th year, and per 5 years afterwards. The 6 SRS-22 domain scores (function, pain, self-image, mental, satisfaction, mean) were compared across time period. RESULTS: All SRS-22 domain scores in post-operative patients, except "Self-image", were relatively stable in the first 5 years until a steady drop starting from the 10th year. "Self-image" was statistically lower than "Function" and "Pain" from the 10th years to more than 30 years. CONCLUSIONS: HRQOL of post-operative AIS patients remained stable until 10 years after surgery and was steadily decreasing. "Self-image" was consistently and statistically lower than the other scores. Patients who have surgically treated for more than 25 years are now at their perimenopause. Specific medical and psychosocial cares for this kind of patients are recommended to provide during the routine medical check-up. LEVEL OF EVIDENCE: II.

Persistent low-normal bone mineral density in adolescent idiopathic scoliosis with different curve severity: A longitudinal study from presentation to beyond skeletal maturity and peak bone mass.

OBJECTIVES: Low bone mineral status has been reported in patients first presented with adolescent idiopathic scoliosis (AIS). We aimed to study whether low-normal bone mineral density (BMD) is persistent among AIS girls during puberty and at peak bone mass, and whether if such persistence is associated with curve severity and differed from healthy controls. METHOD: This prospective longitudinal study comprised 550 AIS girls and 194 healthy control subjects followed from 1997 till 2016. Low-normal BMD was defined as z-standardized bone mineral density (z-BMD) of bilateral femoral neck ≤ -1. Markov Chain 2-stages analysis was conducted to investigate the low-normal BMD transition rate. Linear mixed-effects model and Bland-Altman plot were used to investigate whether low-normal BMD is persistent among a subgroup of AIS patients that reached peak bone mass. RESULTS: The average z-BMD were comparable between AIS cohort and controls at 11 years old (-0.532 vs -0.602), but at 19 years old z-BMD worsened among AIS subjects (-0.860) while controls z-BMD improved (-0.455). During growth period until skeletal maturity, persistence of low-normal BMD was high in both cohorts (>80%) and the AIS group with severe curve presented 100% persistence. Subgroup analysis revealed that z-BMD of AIS patients at skeletal maturity and peak bone mass were highly correlated (r2 = 0.905) and with good agreement. CONCLUSION: AIS patients had poorer BMD that is associated with curve severity and more likely to persist beyond peripubertal period and at peak bone mass when compared to controls.

Is Radiation-Free Ultrasound Accurate for Quantitative Assessment of Spinal Deformity in Idiopathic Scoliosis (IS): A Detailed Analysis With EOS Radiography on 952 Patients.

Radiation exposure with repeated radiography required at follow-up poses serious health concerns for scoliosis patients. Although spinous process angle (SPA) measurement of spinal curvatures with ultrasound has been reported with promising results, an evidence-based account on its accuracy for translational application remains undefined. This prospective study involved 952 idiopathic scoliosis patients (75.7% female, mean age 16.7 ± 3.0 y, Cobb 28.7 ± 11.6°). Among 1432 curves (88.1%) detected by ultrasound, there was good correlation between radiologic Cobb angles measured manually on EOS (E_Cobb) whole-spine radiographs and automatic ultrasound SPA measurement for upper spinal curves (USCs) (r = 0.873, apices T7-T12/L1 intervertebral disc) and lower spinal curves (LSCs) (r = 0.740, apices L1 or below) (p < 0.001). Taller stature was associated with stronger correlation. For E_Cobb <30°, 66.6% USCs and 62.4% LSCs had absolute differences between E_Cobb and predicted Cobb angle calculated from SPA ≤5°. Ultrasound could be a viable option in lieu of radiography for measuring coronal curves with apices at T7 or lower and Cobb angle <30°.

Bone Ninja Mobile App for Reverse Planning Method in Internal Limb Deformity and Lengthening Surgery.

AIM: To report whether Bone Ninja (BN) is a reliable tool to teach the reverse planning method (RPM) for implantable intramedullary (IM) limb-lengthening devices and for deformity correction surgery. BACKGROUND: Motorised fully implantable implantable intramedullary (IM) lengthening devices have been gaining popularity all over the world for limb-lengthening procedures. Multiple advantages have been demonstrated over external fixator-controlled lengthening. Mechanical axis deviation may result if careful preoperative planning and surgical intervention are not completed for femur cases. The RPM proposed by Baumgart has been shown to be an accurate means of arriving at the desired end point. The RPM addresses the ideal correction position accounting for length, angulation, and translation created during lengthening along the nail axis. The original description calls for the use of life-size paper tracings of the bone and large light boxes to allow planning. We propose an alternative method using a digital tool that is readily available. The BN mobile app was developed for patient/physician education and is available for the Apple iPad platform. Bone Ninja has been shown to have similar accuracy for measurements of the limb length and deformity angles when compared to the gold standard picture archiving and communication systems (PACSs). TECHNIQUE: We used BN (version 4.2) on an iPad mini to perform the same RPM steps, using the same terminology originally described by Baumgart. CONCLUSION: Bone Ninja is a simple validated deformity correction tool with accuracy comparable to PACS. It is a reasonable alternative to paper/pencil cutouts for applying RPM for IM limb lengthening and deformity correction surgery. CLINICAL SIGNIFICANCE: We proposed a digitised RPM for internal limb-lengthening surgeries, which is highly feasible and practical to use conveniently without the need for the traditional tedious paper-cutting procedure and related equipment. HOW TO CITE THIS ARTICLE: Hung AL-H, McClure PK, Franzone JM, et al. Bone Ninja Mobile App for Reverse Planning Method in Internal Limb Deformity and Lengthening Surgery. Strategies Trauma Limb Reconstr 2019;14(2):72-76.

Validation Study of the Thumb Ossification Composite Index (TOCI) in Idiopathic Scoliosis: A Stage-to-Stage Correlation with Classic Tanner-Whitehouse and Sanders Simplified Skeletal Maturity Systems.

BACKGROUND: The new simplified thumb ossification composite index (TOCI) based on ossification of the thumb epiphyses and adductor sesamoid has demonstrated simplicity, excellent reliability, and high accuracy for predicting skeletal maturity, comparable with the Sanders simplified skeletal maturity system (SSMS). It was our belief that, because the terminology of the SSMS system has been commonly used for skeletal maturity prediction in idiopathic scoliosis in publications over the past decade, the clinical applicability of the TOCI system would increase if the stages in the 2 systems were found to be interchangeable and highly correlated. METHODS: Hand radiographs of 125 premenarchal girls with newly diagnosed adolescent idiopathic scoliosis who had been followed longitudinally until skeletal maturity were all scored with use of the Tanner-Whitehouse III (TW3) system (stages E through I), the TOCI, and the SSMS. The scores for the epiphyses of the ulnar 4 digits were compared with those for the thumb and correlated with the timing of peak height velocity. Correlations were analyzed with the chi-square test and Cramer V and Somers delta correlations. RESULTS: Six hundred and forty-five hand radiographs (an average of 5 for each girl with idiopathic scoliosis) and 11,517 epiphyses were scored. The rate of concordance between TW3 stages F, G, and I for the thumb proximal phalangeal epiphysis and those for all of the epiphyses of the ulnar 4 digits were 72.5%, 72.5%, and 89.9%, respectively. The overall concordance rate (including all epiphyses) was 71.3%, with a very high Cramer V correlation and significance (p < 0.01). High interchangeability was demonstrated for the TOCI and SSMS stages, supported by a high Somers delta correlation (>0.8) with significance (p < 0.05). CONCLUSIONS: The TOCI is highly practical for clinical use, and its stages are highly interchangeable with those of the SSMS. CLINICAL RELEVANCE: The TOCI could serve as a simplified "marker" of skeletal maturity on hand radiographs and minimize the learning-curve problems associated with the SSMS in a busy clinical practice.

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.