Assessment of craniofacial skeletal maturity is of great importance in orthodontic diagnosis and treatment planning. Traditional radiographic methods suffer from clinician subjectivity and low reproducibility. Recent biochemical methods, such as the use of gingival crevicular fluid (GCF) protein biomarkers involved in bone metabolism, have provided new opportunities to assess skeletal maturity. However, mass spectrometry (MS)-based GCF proteomic analysis still faces significant challenges, including the interference of high abundance proteins, laborious sample prefractionation and relatively limited coverage of GCF proteome. To improve GCF sample processing and further discover novel biomarkers, we herein developed a single-pot, solid-phase-enhanced sample-preparation (SP3)-based high-field asymmetric waveform ion mobility spectrometry (FAIMS)-MS protocol for deep quantitative analysis of the GCF proteome for skeletal maturity indicators. SP3 combined with FAIMS could minimize sample loss and eliminate tedious and time-consuming offline fractionation, thereby simplifying GCF sample preparation and improving analytical coverage and reproducibility of the GCF proteome. A total of 5407 proteins were identified in GCF samples from prepubertal and circumpubertal groups, representing the largest dataset of human GCF proteome to date. Compared to the prepubertal group, 61 proteins were differentially expressed (31 up-regulated, 30 down-regulated) in the circumpubertal group. The six-protein marker panel, including ATP5D, CLTA, CLTB, DNM2, HSPA8 and NCK1, showed great potential to predict the circumpubertal stage (ROC-AUC 0.937), which provided new insights into skeletal maturity assessment.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) affects up to 5% of the population. The efficacy of school-aged screening remains controversial since it is uncertain which curvatures will progress following diagnosis and require treatment. Patient demographics, vertebral morphology, skeletal maturity, and bone quality represent individual risk factors for progression but have yet to be integrated towards accurate prognostication. The objective of this work was to develop composite machine learning-based prediction model to accurately predict AIS curves at-risk of progression.
METHODS: 1870 AIS patients with remaining growth potential were identified. Curve progression was defined by a Cobb angle increase in the major curve of ≥6° between first visit and skeletal maturity in curves that exceeded 25°. Separate prediction modules were developed for i) clinical data, ii) global/regional spine X-rays, and iii) hand X-rays. The hand X-ray module performed automated image classification and segmentation tasks towards estimation of skeletal maturity and bone mineral density. A late fusion strategy integrated these domains towards the prediction of progressive curves at first clinic visit.
RESULTS: Composite model performance was assessed on a validation cohort and achieved an accuracy of 83.2% (79.3-83.6%, 95% confidence interval), sensitivity of 80.9% (78.2-81.9%), specificity of 83.6% (78.8-84.1%) and an AUC of 0.84 (0.81-0.85), outperforming single modality prediction models (AUC 0.65-0.78).
CONCLUSIONS: The composite prediction model achieved a high degree of accuracy. Upon incorporation into school-aged screening programs, patients at-risk of progression may be prioritized to receive urgent specialist attention, more frequent follow-up, and pre-emptive treatment.
BACKGROUND: Funding from The Society for the Relief of Disabled Children was awarded to GKHS.

The proximal humeral epiphyses can be conveniently viewed in routine spine radiographs. This study aimed to investigate whether the proximal humeral epiphyseal ossification system (PHOS) can be used to determine the timing of brace weaning in adolescent idiopathic scoliosis (AIS), as assessed by the rate of curve progression after brace weaning.
A total of 107 patients with AIS who had weaned brace-wear at Risser Stage  ≥  4, no bodily growth and post-menarche  ≥  2 years between 7/2014 and 2/2016 were studied. Increase in major curve Cobb angle > 5° between weaning and 2-year follow-up was considered curve progression. Skeletal maturity was assessed using the PHOS, distal radius and ulna (DRU) classification, Risser and Sanders staging. Curve progression rate per maturity grading at weaning was examined.
After brace-wear weaning, 12.1% of the patients experienced curve progression. Curve progression rate for weaning at PHOS Stage 5 was 0% for curves < 40°, and 20.0% for curves ≥ 40°. No curve progression occurred when weaning at PHOS Stage 5 with radius grade of 10 for curves ≥ 40°. Factors associated with curve progression were: Months post-menarche (p = 0.021), weaning Cobb angle (p = 0.002), curves < 40° versus ≥ 40° (p = 0.009), radius (p = 0.006) and ulna (p = 0.025) grades, and Sanders stages (p = 0.025), but not PHOS stages (p = 0.454).
PHOS can be a useful maturity indicator for brace-wear weaning in AIS, with PHOS Stage 5 having no post-weaning curve progression in curves < 40°. For large curves ≥ 40°, PHOS Stage 5 is also effective in indicating the timing of weaning together with radius grade ≥ 10.

UNASSIGNED: Skeletal maturity can evaluate the growth and development potential of children and provide a guide for the management of adolescent idiopathic scoliosis (AIS). Recent studies have demonstrated the advantages of the Humeral Head Ossification System (HHOS) and the Proximal Femur Maturity Index (PFMI), based on standard scoliosis films, in the management of AIS patients. We further assessed the HHOS and the PFMI method\'s reliability in the interrater and intrarater.
UNASSIGNED: The data from 38 patients, including the humeral head and proximal femur on standard scoliosis films, were distributed to the eight raters in the form of a PowerPoint presentation. On 38 independent standard spine radiographs, raters utilized the HHOS and PFMI to assign grades. The PPT sequence was randomly changed and then reevaluated 2 weeks later. For every system, the 95% confidence interval (95% CI) and intraclass correlation coefficient (ICC) were calculated to evaluate the interrater and intrarater reliability.
UNASSIGNED: The HHOS was extremely reliable, with an intraobserver ICC of 0.802. In the first round, the interobserver ICC reliability for the HHOS was 0.955 (0.929-0.974), while in the second round, it was 0.939 (0.905-0.964). The PFMI was extremely reliable, with an intraobserver ICC of 0.888. In the first round, the interobserver ICC reliability for the PFMI was 0.967 (0.948-0.981), while in the second round, it was 0.973 (0.957-0.984).
UNASSIGNED: The HHOS and PFMI classifications had excellent reliability. These two methods are beneficial to reduce additional exposure to radiation and expense for AIS. There are advantages and disadvantages to each classification. Clinicians should choose a personalized and reasonable method to assess skeletal maturity, which will assist in the management of adolescent scoliosis patients.

UNASSIGNED: Bone age assessment (BAA) is a crucial research topic in pediatric radiology. Interest in the development of automated methods for BAA is increasing. The current BAA algorithms based on deep learning have displayed the following deficiencies: (I) most methods involve end-to-end prediction, lacking integration with clinically interpretable methods; (II) BAA methods exhibit racial and geographical differences.
UNASSIGNED: A novel, automatic skeletal maturity assessment (SMA) method with clinically interpretable methods was proposed based on a multi-region ensemble of convolutional neural networks (CNNs). This method predicted skeletal maturity scores and thus assessed bone age by utilizing left-hand radiographs and key regional patches of clinical concern.
UNASSIGNED: Experiments included 4,861 left-hand radiographs from the database of Beijing Jishuitan Hospital and revealed that the mean absolute error (MAE) was 31.4±0.19 points (skeletal maturity scores) and 0.45±0.13 years (bone age) for the carpal bones-series and 29.9±0.21 points and 0.43±0.17 years, respectively, for the radius, ulna, and short (RUS) bones series based on the Tanner-Whitehouse 3 (TW3) method.
UNASSIGNED: The proposed automatic SMA method, which was without racial and geographical influence, is a novel, automatic method for assessing childhood bone development by utilizing skeletal maturity. Furthermore, it provides a comparable performance to endocrinologists, with greater stability and efficiency.

OBJECTIVE: Nowadays, the integration of Artificial intelligence algorithms and quantified radiographic imaging-based diagnostic procedures is hailing amplified deliberation particularly in assessment of skeletal maturity. So we intend to formulate a logistic regression model for intelligent and quantitative estimation of Fishman skeletal maturation index (SMI) based on the parameters attained from the cervical vertebrae CBCT images of Chinese girls.
METHODS: From 709 hand wrist radiographs and CBCT images, 447 samples were randomly selected (called as G1) to build a logistic regression model. The reliability and reproducibility were assessed by the intraclass correlation coefficient (ICC) and weighted Cohen\'s kappa, followed by Spearman\'s rank correlation coefficient to identify the parameters significantly associated with the SMI. Two hundred and sixty-two other subjects (named G2) were recruited for external examination of the models by direct visual comparison and the receiver operating characteristic (ROC) curve. In cases of confusion and mispredictions, the model was modified to improve the consistency.
RESULTS: Five significant parameters (Chronological age, C3 height (H3)[Formula: see text], C4 upper width (UW4), C4 lower width (LW4), and the ratio of posterior height to lower width of C4 ([Formula: see text]) were administered into logistic regression model. Despite total agreement percentage which was 84% (total AUC = 0.92), unsatisfactory performance was noticed for the 6th and 8th stages which were confused with their neighboring stages. After adjustments of the models, the total agreement percentage and AUC were upgraded to 88% and 0.96, respectively.
CONCLUSIONS: Consistency and fitness evaluation of our models demonstrated adequate prediction percentage and reliability for automated classification of skeletal maturation. The presented constructed logistic regression model has the potential to serve as a maturity evaluation index in clinical craniofacial orthopedics in Chinese girls. The proposed model in this study showed promising strength for being expended in the event of other clinical multi-stage conditions.

OBJECTIVE: The aim of this study was to investigate whether including the stages of ulnar physeal closure in Sanders stage 7 aids in a more accurate assessment for brace weaning in patients with adolescent idiopathic scoliosis (AIS).
METHODS: This was a retrospective analysis of patients who were weaned from their brace and reviewed between June 2016 and December 2018. Patients who weaned from their brace at Risser stage ≥ 4, had static standing height and arm span for at least six months, and were ≥ two years post-menarche were included. Skeletal maturity at weaning was assessed using Sanders staging with stage 7 subclassified into 7a, in which all phalangeal physes are fused and only the distal radial physis is open, with narrowing of the medial physeal plate of the distal ulna, and 7b, in which fusion of > 50% of the medial growth plate of distal ulna exists, as well as the distal radius and ulna (DRU) classification, an established skeletal maturity index which assesses skeletal maturation using finer stages of the distal radial and ulnar physes, from open to complete fusion. The grade of maturity at the time of weaning and any progression of the curve were analyzed using Fisher\'s exact test, with Cramer\'s V, and Goodman and Kruskal\'s tau.
RESULTS: We studied a total of 179 patients with AIS, of whom 149 (83.2%) were female. Their mean age was 14.8 years (SD 1.1) and the mean Cobb angle was 34.6° (SD 7.7°) at the time of weaning. The mean follow-up was 3.4 years (SD 1.8). At six months after weaning, the rates of progression of the curve for patients weaning at Sanders stage 7a and 7b were 11.4% and 0%, respectively for those with curves of < 40°. Similarly, the rates of progression of the curve for those being weaned at ulnar grade 7 and 8 using the DRU classification were 13.5% and 0%, respectively. The use of Sanders stages 6, 7a, 7b, and 8 for the assessment of maturity at the time of weaning were strongly and significantly associated (Cramer\'s V 0.326; p = 0.016) with whether the curve progressed at six months after weaning. Weaning at Sanders stage 7 with subclassification allowed 10.6% reduction of error in predicting the progression of the curve.
CONCLUSIONS: The use of Sanders stages 7a and 7b allows the accurate assessment of skeletal maturity for guiding brace weaning in patients with AIS. Weaning at Sanders stage 7b, or at ulnar grade 8 with the DRU classification, is more appropriate as the curve did not progress in any patient with a curve of < 40° immediately post-weaning. Thus, reaching full fusion in both distal radial and ulnar physes (as at Sanders stage 8) is not necessary and this allows weaning from a brace to be initiated about nine months earlier. Cite this article: Bone Joint J 2021;103-B(1):141-147.

UNASSIGNED: Retrospective cohort study.
UNASSIGNED: To explore the possibility of predicting final body height at maturity based on associating parameters at the time of diagnosing adolescent idiopathic scoliosis (AIS), while examining the effect of curve magnitude and deterioration.
UNASSIGNED: A total of 284 female patients with AIS (mean age 12.2 ± 1.1 years, 52.5% premenarchal) were followed till skeletal maturity, indicated by ≥Risser stage 4, static body height and arm span over the past 6 months, and postmenarche 2 years. Standing body height, arm span, menarchal status, Risser staging, distal radius and ulna (DRU) classification, Sanders staging (SS), Cobb angles (major and minor curves), and Lenke curve types at initial presentation were examined. Patients with/without curve deterioration were compared. Multiple linear regression was used for predicting final body height (cm), and remaining height increase (%).
UNASSIGNED: Baseline body height was 152.1 ± 7.1 cm and major curve Cobb angle was 27.1° ± 7.4°, whereas at maturity they were 159.5 ± 5.4 cm and 32.5° ± 9.3°, respectively. For patients presented at Risser stage 0 or 1, radius grade (R) 6, ulnar grade (U) 5, or SS3, those with curve deterioration exhibited greater height increase potential at initial presentation (P < .05) than those without deterioration. No intergroup difference was found for patients presented at ≥Risser 2, R7, U6, SS4. Predictive baseline parameters were age, body height, Cobb angle (major curve), curve type, and DRU grades. Prediction models of final body height (R 2 = 0.735, P < .001) and remaining height increase (R 2 = 0.742, P < .001) were established.
UNASSIGNED: Final body height prediction model was derived for female patients with AIS, with baseline body height and ulnar grading having larger impacts than other parameters.

BACKGROUND: Radiographic methods in evaluating the skeletal maturity include Risser sign and Tanner-Whitehouse score. They are either inappropriate or too complex for a busy clinic setting. The cervical vertebral maturation (CVM) stage is commonly used in orthodontics but has been less acknowledged in studies of spinal growth. The purpose of this study was to evaluate whether the CVM stage could be used as an alternative to Risser sign in determining peak height velocity (PHV).
METHODS: This was a two-stage study. Inclusion criteria for stage I study were adolescent female idiopathic scoliosis (AIS) patients, aged between 9-16 years old, who had undergone full spine imaging with clear visibility of the cervical spine. Patients in the stage II study had follow-up through CVM stage 2-4. The correlation between CVM and Risser was analyzed. The spinal growth parameters were measured at each follow-up, and the growth velocity of parameters (PaGVs) was calculated. The PaGVs at CVM stage 2-4 were further compared.
RESULTS: A total of 170 AIS patients were included for stage I study (mean age 12.7 years). The CVM stages were found to correlate strongly with the Risser sign (r=0.85, P<0.01). For those patients with Risser stage 0 with closed TC, 71% were CVM stage 3. Fifty-one patients were included for stage II study. The stature growth velocity averaged 5.4 cm/year in CVM stage 2 patients and 6.3 cm/year in CVM stage 3 patients, which was significantly greater growth than that in CVM stage 4 patients (3.3 cm/year, both P<0.01); similarly, the growth velocity of arm span, trunk height, and spinal lengths were also significantly higher in CVM stage 3 patients compared to CVM stage 2 and 4 patients.
CONCLUSIONS: The CVM stage could provide an alternative option for the assessment of skeletal maturity of subjects with idiopathic scoliosis. CVM stage 3 may be a new sign of PHV.

Study Design Prospective radiographic study. Objective To test the reliability of the Distal Radius and Ulna Classification (DRU). Methods This single-center study included prospectively recruited subjects with adolescent idiopathic scoliosis managed with bracing. The left-hand radiographs were measured using the DRU classification by two examiners. Intra- and interobserver reliability analysis were performed using intraclass correlation (ICC) analysis. Results From these clinics, 161 patients (124 females and 37 males) with left-hand radiographs were included in the study. The mean age was 13.3 years (standard deviation: 1.5). There was excellent intra- (ICC: 0.93 to 0.95) and interobserver (ICC: 0.97) reliability. Conclusions The DRU classification scheme has been shown to be accurate in determining the peak growth phase and growth cessation. It has now been confirmed to be a reliable tool. Future prospective studies should be performed to investigate its application in deciding when to apply bracing or operative treatment.