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Dolan LA, Weinstein SL, Dobbs MB, Flynn JMJ, Green DW, Halsey MF, Hresko MT, Krengel WF, Mehlman CT, Milbrandt TA, Newton PO, Price N, Sanders JO, Schmitz ML, Schwend RM, Shah SA, Song K, Talwalkar V. BrAIST-Calc: Prediction of Individualized Benefit From Bracing for Adolescent Idiopathic Scoliosis. Spine (Phila Pa 1976) 2024; 49:147-156. [PMID: 37994691 PMCID: PMC10841822 DOI: 10.1097/brs.0000000000004879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 11/13/2023] [Indexed: 11/24/2023]
Abstract
STUDY DESIGN Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data. OBJECTIVE Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models. MATERIALS AND METHODS Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration. RESULTS The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83-0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%. CONCLUSION This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population.
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Affiliation(s)
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- Carelon Health Services and the University of California, Los Angeles, CA
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Faldini C, Manzetti M, Neri S, Barile F, Viroli G, Geraci G, Ursini F, Ruffilli A. Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature. Int J Mol Sci 2022; 23:5914. [PMID: 35682604 PMCID: PMC9180299 DOI: 10.3390/ijms23115914] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/18/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.
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Affiliation(s)
- Cesare Faldini
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
| | - Marco Manzetti
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
| | - Simona Neri
- Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy;
| | - Francesca Barile
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
| | - Giovanni Viroli
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
| | - Giuseppe Geraci
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
| | - Francesco Ursini
- Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy;
- Department of Biomedical and Neuromotor Science—DIBINEM, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy
| | - Alberto Ruffilli
- Department of Biomedical and Neuromotor Science-DIBINEM, 1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, University of Bologna, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy; (C.F.); (M.M.); (F.B.); (G.V.); (G.G.); (A.R.)
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Kikanloo SR, Tarpada SP, Cho W. Etiology of Adolescent Idiopathic Scoliosis: A Literature Review. Asian Spine J 2019; 13:519-526. [PMID: 30744305 PMCID: PMC6547389 DOI: 10.31616/asj.2018.0096] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Accepted: 08/15/2018] [Indexed: 12/18/2022] Open
Abstract
Adolescent idiopathic scoliosis (AIS) is the peripubertal development of spinal curvature of a minimum of 10°. AIS is thought to be attributable to genetic factors, nutrition, early exposure to toxins, and hormonal dysregulation. Recent literature suggests these factors may compound to determine both disease onset and severity. Currently, treatment is limited to observation, bracing, and surgical intervention. Intervention is presently determined by severity and risk of curve progression. As they emerge, new therapies may target specific etiologies of AIS.
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Affiliation(s)
- Sina Rashidi Kikanloo
- Department of Orthopedic Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
| | - Sandip Parshottam Tarpada
- Department of Orthopedic Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
| | - Woojin Cho
- Department of Orthopedic Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
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Positive Association between TGFB1 Gene and Susceptibility to Idiopathic Scoliosis in Bulgarian Population. Anal Cell Pathol (Amst) 2018; 2018:6836092. [PMID: 30079294 PMCID: PMC6069583 DOI: 10.1155/2018/6836092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 05/08/2018] [Accepted: 06/12/2018] [Indexed: 11/17/2022] Open
Abstract
Idiopathic scoliosis (IS) is a common medical condition beginning in childhood and characterized by strong evidence for a genetic susceptibility to three-dimensional spinal deformity. The primary goal of the current case-control study is to examine the association between the TGFB1 (-509C/T) functional polymorphic variant and genetic predisposition to IS in the Bulgarian population and the genotype-phenotype correlations in distinct case-control subgroups based on age at onset, family history, and gender. A total of 127 patients with primary scoliosis and 254 gender-matched control subjects were recruited. The mean Cobb angle was 53.8 ± 21.2°. Genotyping of cases and controls was performed using the TaqMan real-time amplification technique. The results were processed statistically using Pearson's Chi-squared test and Fisher's exact test with a value of p less than 0.05 as statistically significant. The polymorphic T allele and TT genotype were associated with a greater incidence of IS and can be considered as predisposing factors with a moderate effect on deformity development. The current results suggested that there was a genetic predisposition in early and late onset IS and familial, sporadic, and female cases. Nevertheless, replication studies are needed to reveal the relationship between the TGFB1 locus and certain subtypes of IS in different populations.
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High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9784083. [PMID: 30079352 PMCID: PMC6069699 DOI: 10.1155/2018/9784083] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 05/30/2018] [Accepted: 06/11/2018] [Indexed: 01/01/2023]
Abstract
Background Adolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated. Materials and Methods Circulating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls. Results A significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12 ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02 ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11 ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (≥7.30 ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48 ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821). Conclusions High ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.
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Brace Treatment for Adolescent Idiopathic Scoliosis. J Clin Med 2018; 7:jcm7060136. [PMID: 29867010 PMCID: PMC6024899 DOI: 10.3390/jcm7060136] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 05/23/2018] [Accepted: 05/29/2018] [Indexed: 11/17/2022] Open
Abstract
In the past, numerous non-operative treatments for adolescent idiopathic scoliosis (AIS), including exercise, physical therapy, electrical stimulation, and brace treatment, have been tried to delay or prevent the curve progression. Of these, brace treatment is the only option that is widely accepted and has demonstrated the efficacy to alter the natural history of AIS. Recently, the importance of brace treatment for AIS has been increasing since the efficacy was objectively established by the BrAIST (Bracing in Adolescent Idiopathic Scoliosis Trial) study in 2013. This editorial article summarizes the current status of brace treatment in patients with AIS and discusses future prospects on the basis of our clinical experiences.
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Noshchenko A, Hoffecker L, Lindley EM, Burger EL, Cain CMJ, Patel VV, Bradford AP. Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis. World J Orthop 2015; 6:537-558. [PMID: 26301183 PMCID: PMC4539477 DOI: 10.5312/wjo.v6.i7.537] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Revised: 05/14/2015] [Accepted: 06/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.
METHODS: Selection criteria: (1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other. Search method: Ovid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.
RESULTS: The review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25o); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.
CONCLUSION: This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.
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Zhao L, Roffey DM, Chen S. Genetics of adolescent idiopathic scoliosis in the post-genome-wide association study era. ANNALS OF TRANSLATIONAL MEDICINE 2015; 3:S35. [PMID: 26046082 DOI: 10.3978/j.issn.2305-5839.2015.03.54] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 02/20/2015] [Indexed: 11/14/2022]
Affiliation(s)
- Linlu Zhao
- 1 Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada ; 2 University of Ottawa Spine Program, The Ottawa Hospital, Ottawa, ON, Canada ; 3 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Darren M Roffey
- 1 Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada ; 2 University of Ottawa Spine Program, The Ottawa Hospital, Ottawa, ON, Canada ; 3 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Suzan Chen
- 1 Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada ; 2 University of Ottawa Spine Program, The Ottawa Hospital, Ottawa, ON, Canada ; 3 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
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Kuroki H, Inomata N, Hamanaka H, Higa K, Chosa E, Tajima N. Predictive factors of Osaka Medical College (OMC) brace treatment in patients with adolescent idiopathic scoliosis. SCOLIOSIS 2015; 10:11. [PMID: 25873992 PMCID: PMC4395903 DOI: 10.1186/s13013-015-0038-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 03/31/2015] [Indexed: 11/10/2022]
Abstract
Background Factors influencing clinical course of brace treatment apply to adolescent idiopathic scoliosis (AIS) patients remain unclear. By making clear them, we may select suitable patients for brace treatment and alleviate overtreatment. The purpose of this study was to explore predictive factors of Osaka Medical College (OMC) brace treatment for AIS patients in accordance with the modified standardized criteria proposed by the Scoliosis Research Society (SRS) committee on bracing and non-operative management. Methods From 1999 through 2010, 31 consecutive patients with AIS who were newly prescribed the OMC brace and met the modified SRS criteria were studied. The study included 2 boys and 29 girls with a mean age of 12 years and 0 month. We investigated the clinical course and evaluated the impacts of compliance, initial brace correction rate, curve flexibility, curve pattern, Cobb angle, chronological age, and Risser stage to clinical outcomes. The clinical course of the brace treatment was considered progression if ≥6° curvature increase occurred and improvement if ≥6° curvature decrease occurred according to SRS judgment criteria. Results The curve progressed in 10 cases, the curve improved in 6 cases, and the curve remained unchanged in 15 cases (success rate: 67.7%). The success rate was statistically higher in the patient group whose instruction adherence rate was greater than 50% as compared with in those 50% or less. Initial brace correction rate, curve flexibility, curve pattern, the magnitude of Cobb angle, chronological age, and Risser stage did not have any significant effect for clinical courses. However, success rate was insignificantly higher in the cases whose Cobb angle in brace was smaller than that in hanging position. Conclusions OMC brace treatment could alter the natural history of AIS, however, that was significantly affected by compliance of brace wear.
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Affiliation(s)
- Hiroshi Kuroki
- Department of Orthopaedic Surgery, National Hospital Organization Miyazaki Higashi Hospital, 4374-1 Tayoshi Ooaza, Miyazaki, 880-0911 Japan
| | - Naoki Inomata
- Department of Orthopaedic Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | - Hideaki Hamanaka
- Department of Orthopaedic Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | - Kiyoshi Higa
- Department of Orthopaedic Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | - Etsuo Chosa
- Department of Orthopaedic Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan
| | - Naoya Tajima
- Department of Orthopaedic Surgery, Nozaki Higashi Hospital, Miyazaki, Japan
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