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Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis.

ABSTRACT: PURPOSE: To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment. METHOD: A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outcome of brace treatment (success/failure). The failure of brace treatment was defined as a curve progression of more than 5° compared to the initial Cobb angle or surgical intervention because of curve progression. Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor ? (ER?), estrogen receptor ? (ER?), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AIS, were selected for genotyping by the PCR-RFLP method. Differences of genotype and allele distribution between the two groups were compared by the ?(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment. RESULTS: There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p < 0.001) and the G allele (27.1 vs. 12.0%, p < 0.001) at SNP rs9340799 of the ER? gene. Similarly, they were also associated with the genotype AT (33.3 vs. 13.0%, p = 0.002) and the A allele (16.7 vs. 9.6%, p = 0.033) at SNP rs10488682 of the TPH-1 gene. For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ER? genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ER? and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. CONCLUSIONS: ER? and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment. Patients with the G allele at the rs9340799 site of the ER? gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

SUBMITTER: Xu L

PROVIDER: S-EPMC3175878 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis.

Xu Leilei L Qiu Xusheng X Sun Xu X Mao Saihu S Liu Zhen Z Qiao Jun J Qiu Yong Y

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 20110621 10

<h4>Purpose</h4>To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment.<h4>Method</h4>A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outc ...[more]

PMID: 21691901

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Project description:PurposeBrace treatment for adolescent idiopathic scoliosis (AIS) is usually prescribed for 20-40° curves in patients with growth potential. The aim is to reduce the risk of curve progression during growth and to avoid the curve reaching a surgical threshold. Having as small a curve as possible at skeletal maturity will reduce the risk of curve progression during adult life. While evidence exists for brace treatment in AIS, there is disagreement on how and when to discontinue bracing. The purpose of this review was to investigate what criteria have been reported for initiating brace cessation and published weaning protocols and to look at estimates of the number of patients that may progress > 5 degrees after the end of growth.MethodsThis scoping review summarizes existing knowledge on the best time to stop bracing in AIS patients, how to "wean," and what happens to spinal curves after bracing. Searches were carried out through MEDLINE, EMBASE, and PsycINFO in April 2022. A total of 1936 articles were reduced to 43 by 3 reviewers. Full papers were obtained, and data were extracted.ResultsWeaning was most commonly determined by Risser 4 (girls) and 5 (boys). Other requirements included 2 years post-menarche and no growth in standing/sitting height for 6 months. Skeletal maturity assessed from hand and wrist radiographs, e.g., Sanders' stage; distal radius and ulnar physes, could determine the optimal weaning time to minimize curve progression. Complete discontinuation was the most common option at skeletal maturity; variations on weaning protocols involved gradual reduction of bracing over 6-12 months. Curve progression after weaning is common. The 12 studies reporting early curve progression after brace weaning found a mean Cobb angle progression of 3.8° (n = 1655). From the seven studies reporting early curve progression by > 5 degrees, there were 236/700 (34%) patients. There is limited information on risk factors to predict early curve progression after finishing brace treatment with larger curves, especially those over 40 degrees possibly having more chance of progression.ConclusionCurve progression after bracing cessation is a negative outcome for patients who have tolerated bracing for several years, especially if surgery is required. The literature shows that when to start brace cessation and weaning protocols vary. Approximately 34% of patients progressed by more than 5 degrees at 2-4 years after brace cessation or weaning. Larger curves seem more likely to progress. More research is needed to evaluate the risk factors for curve progression after brace treatment, defining the best time to stop bracing based on the lowest risk of curve progression and whether there is any benefit to weaning.

Project description:BACKGROUND:Four factors have been reported to affect brace treatment outcome: (1) growth or curve based risk, (2) the in-brace correction, (3) the brace wear quantity, and (4) the brace wear quality. The quality of brace design affects the in-brace correction and comfort which indirectly affects the brace wear quantity and quality. This paper reported the immediate benefits and results on using ultrasound (US) to aid orthotists to design braces for the treatment of scoliosis. METHODS:Thirty-four AIS subjects participated in this study with 17 (2 males, 15 females) in the control group and 17 (2 males, 15 females) in the intervention (US) group. All participants were prescribed full time TLSO, constructed by either of the 2 orthotists in fabrication of spinal braces. For the control group, the Providence brace design system was adopted to design full time braces. For the intervention group, the custom standing Providence brace design system, plus a medical ultrasound system, a custom pressure measurement system and an in-house software were used to assist brace casting. RESULTS:In the control group, 8 of 17 (47%) subjects needed a total of 11 brace adjustments after initial fabrication requiring a total of 28 in-brace radiographs. Three subjects (18%) required a second adjustment. For the US group, only 1 subject (6%) required adjustment. The total number of in-brace radiographs was 18. The p value of the chi-square for requiring brace adjustment was 0.006 which was a statistically significant difference between the two groups. In the intervention group, the immediate in-brace correction as measured from radiographs was 48?±?17%, and in the control group the first and second in-brace correction was 33?±?19% and 40?±?20%, respectively. The unpaired 2 sided Student's t test of the in-brace correction was significantly different between the US and the first follow-up of the control group (p?=?0.02), but was not significant after the second brace adjustment (p?=?0.22). CONCLUSIONS:The use of the 3D ultrasound system provided a radiation-free method to determine the optimum pressure level and location to assist brace design, resulting in decreased radiation exposure during follow-up brace evaluation, increased the in-brace correction, reduced the patients' visits to both brace adjustment and scoliosis clinics. However, the final outcomes could not be reported yet as some of patients are still under brace treatment. TRIAL REGISTRATION:NCT02996643, retrospectively registered in 16 December 2016.

Project description:It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment.272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%) patients had late-onset juvenile and 214 had adolescent idiopathic scoliosis. All patients had clinical and radiological examination and answered a standardised questionnaire including work status, demographics, General Function Score (GFS) (100 - worst possible) and Oswestry Disability Index (ODI) (100 - worst possible), EuroQol (EQ-5D) (1 - best possible), EQ-VAS (100 - best possible), and Scoliosis Research Society - 22 (SRS - 22) (5 - best possible).The mean age at follow-up was 40.4 (31-48) years. The prebrace major curve was in average 33.2 (20 - 57)°. At weaning and at the last follow-up the corresponding values were 28.3 (1 - 58)° and 32.5 (7 - 80)°, respectively. Curve development was similar in patients with late-onset juvenile and adolescent start. The prebrace curve increased > 5° in 31% and decreased > 5° in 26%. Twenty-five patients had surgery. Those who did not attend follow-up (n = 88) had a lower mean curve at weaning: 25.4 (6-53)°. Work status was 76% full-time and 10% part-time. Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean (SD) GFS was 7.4 (10.8), ODI 9.3 (11.0), EQ-5D 0.82 (0.2), EQ-VAS 77.6 (17.8), SRS-22: pain 4.1 (0.8), mental health 4.1 (0.6), self-image 3.7 (0.7), function 4.0 (0.6), satisfaction with treatment 3.7 (1.0). Surgical patients had significantly reduced scores for SRS-physical function and self-image, and patients with curves ? 45° had reduced self-image.Long-term results were satisfactory in most braced patients and similar in late-onset juvenile and idiopathic adolescent scoliosis.

Project description:Over the last years, evidence has accumulated in support of bracing as an effective treatment option in patients with idiopathic scoliosis. Yet, little information is available on the impact of compliance on the outcome of conservative treatment in scoliotic subjects. The aim of the present study was to prospectively evaluate the association between compliance to brace treatment and the progression of scoliotic curve in patients with idiopathic adolescent (AIS) or juvenile scoliosis (JIS).Among 1.424 patients treated for idiopathic scoliosis, 645 were eligible for inclusion criteria. Three outcomes were distinguished in agreement with the SRS criteria: curve correction, curve stabilization and curve progression. Brace wearing was assessed by one orthopaedic surgeon (LA) and scored on a standardized form. Compliance to treatment was categorized as complete (brace worn as prescribed), incomplete A (brace removed for 1 month), incomplete B (brace removed for 2 months), incomplete C (brace removed during school hours), and incomplete D (brace worn overnight only). Chi square test, T test or ANOVA and ANOVA for repeated measures tests were used as statistical tests.The results from our study showed that at follow-up the compliance was: Complete 61.1%; Incomplete A 5.2%; Incomplete B 10.7%; Incomplete C 14.2%; Incomplete D 8.8%. Curve correction was accomplished in 301/319 of Complete, 19/27 Incomplete A, 25/56 Incomplete B, 52/74 Incomplete C, 27/46 Incomplete D. Cobb mean value was 29.8?±?7.5 SD at beginning and 17.1?±?10.9 SD at follow-up. Both Cobb and Perdriolle degree amelioration was significantly higher in patients with complete compliance over all other groups, both in juvenile, both in adolescent scoliosis. In the intention-to-treat analysis, the rate of surgical treatment was 2.1% among patients with definite outcome and 12.1% among those with drop-out. Treatment compliance showed significant interactions with time.Curve progression and referral to surgery are lower in patients with high brace compliance. Bracing discontinuation up to 1 month does not impact on the treatment outcome. Conversely, wearing the brace only overnight is associated with a high rate of curve progression.

Project description:BackgroundScoliotic braces are the standard of curve for management of moderate spinal deformities in pediatric patients. The effectiveness of this treatment method has been shown; however, the spinal and rib cage parameters, in the three anatomical planes, that are associated with bracing outcome in adolescent idiopathic scoliosis (AIS) are not fully identified.MethodsA total number of 45 right thoracic AIS patients who had received a thoraco-lumbo-scaral brace for the first time were included retrospectively. For each patient, radiographic images at three visits, pre-brace, in-brace, and at least 1 year after the first brace fit were included. Age, sex, Risser sign, and curve type at pre-brace, and thoracic and lumbar frontal and sagittal Cobb angles, thoracic and lumbar apical rotations, sagittal and frontal balances at pre-brace and in-brace were determined. Two sagittal curve types (hypothoracolumbar and normal/hyperthoracolumbar kyphosis), two rib cage types based on the costovertebral joints (drooping and horizontal), and two axial shapes of the spine (S shaped and V shaped) were used to stratify the patients. Feature selection and linear regression with regularization determined the parameters and the interaction terms that predicted the brace effectiveness significantly.ResultsSmaller in-brace thoracic Cobb and larger in-brace lordosis predicted brace effectiveness, p < 0.05. Impact of the out of brace lordosis on the brace success increased as the in brace kyphosis angle decreased, p = 0.046. A larger out of brace lordosis in hypothoracolumbar sagittal profile type patients improved the outcomes, p = 0.031. A smaller out of brace thoracic rotation improved the bracing outcomes in patients with horizontal ribs, p = 0.040.ConclusionBoth 3D patient specific parameters (lordosis, thoracic rotation, shape of the rib cage, and sagittal profile) and brace design (which allows larger in brace lordosis, better in brace Cobb correction) are important predictors of the brace effectiveness in AIS.

Project description:IntroductionAdolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine. Brace treatment is effective for eligible patients with AIS and the effectiveness is significantly correlated with the average brace-wear time per day. Three-dimensional (3D) printing technology is a recent advancement that offers unique opportunities for biomedical applications, and customisation of scoliosis braces might lead to greater patient satisfaction and improved compliance. We present here the design of a randomised controlled trial on the clinical effectiveness of 3D-printed braces versus thoracolumbosacral orthoses (TLSO) for patients with AIS.Methods and analysisPatients with AIS (age 10-16 years) with Risser sign 0-II, Cobb angle of main curve of 20°-40°, premenarchal or no more than 1-year postmenarchal (for women), and no history of treatment are eligible, unless they are unable to tolerate the treatment or refuse participation. A total of 88 patients will be randomised into either the 3D group or TLSO group on a 1:1 basis. Participants in the 3D group will choose between a 3D-printed brace and TLSO, according to the Zelen's design of the trial. Primary outcome measures will include the average brace-wear time per day, health-related quality of life and Cobb angle progression of the primary curve. Secondary outcome measures will include immediate in-brace correction of Cobb angle of the primary curve, rate of conversion to surgery and incidence of any adverse events. This study is designed as a single-centre, two-arm, superiority and open-label randomised controlled trial. The sample size is calculated with reference to the preliminary study and based on the sample size calculation formula.Ethics and disseminationThis study was approved by the Peking University Third Hospital Medicine Science Research Ethics Committee (No: 2019-017-02). Results of the trial will be submitted for publication in a peer-reviewed journal and as conference presentations.Trial registration numberChiCTR1900027379, pre-results.

Project description:BackgroundThe Proximal Femur Maturity Index (PFMI) can be used to assess skeletal maturity on existing whole-spine radiographs without additional radiation. However, the relationship between the PFMI at the initiation of bracing for adolescent idiopathic scoliosis (AIS) and subsequent curve progression remains unknown. This study aimed to investigate the relationship between the PFMI and curve progression, and the predictability of risks to adulthood curve progression and surgical thresholds based on the PFMI grade at brace initiation.MethodsThis was a prospective study of 202 patients with AIS who were prescribed underarm bracing according to the Scoliosis Research Society criteria and had good brace-wear compliance. The patients were followed from brace initiation until complete skeletal maturity. Longitudinal data on the coronal Cobb angle and skeletal maturity assessments using Risser staging, Sanders staging, the distal radius and ulna classification, and the PFMI were collected. Each patient was assessed on whether the major curve progressed to ≥40° (adulthood deterioration) and ≥50° (the surgical threshold). Logistic regressions were used to predict probabilities of curve progression to the 2 thresholds, adjusted for factors that were significant in univariate analyses.ResultsThe PFMI correlated with the other skeletal maturity indices (r s [Spearman rank correlation] = 0.60 to 0.72, p < 0.001 for all). The pre-brace PFMI grade correlated with progression to ≥40° (r rb [rank-biserial correlation] = -0.30, p < 0.001) and to ≥50° (r rb = -0.20, p = 0.005). Based on regression models (p < 0.001) adjusted for the pre-brace major Cobb angle and curve type, brace initiation at PFMI grades 2 and 3 for a curve of ≥30° had predicted risks of 30% (95% confidence interval [CI], 4% to 55%) and 12% (95% CI, 7% to 17%), respectively, for progression to the surgical threshold. Brace initiation at PFMI grade 5 had 0% progression risk.ConclusionsThe PFMI can be used for predicting curve progression and prognosticating brace outcomes in AIS. Patients with brace initiation at PFMI grade 4 for a curve of <30° or at grade 5 were unlikely to progress to the adulthood deterioration or surgical threshold. In comparison, skeletally immature patients initiating bracing at a PFMI grade of ≤3 for a major curve of ≥30° had a higher risk of progression despite compliant brace wear.Level of evidencePrognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

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Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis.

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Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis.

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