Re: Ward K, Ogilvie JW, Singleton MV, et al. Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis. Spine 2010;35:E1455-64.

Associate Professor, Washington University School of Medicine Department of Orthopaedic Surgery Saint Louis, Missouri (Dobbs) Assistant Professor, Washington University School of MedicineDepartments of Neurology, Pediatrics, and Orthopaedic SurgerySaint Louis, Missouri (Gurnett).
Spine (Impact Factor: 2.3). 07/2011; 36(15):1257; author reply 1257. DOI: 10.1097/BRS.0b013e31821987ba
Source: PubMed
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    ABSTRACT: Study Design. A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS).Objective. To determine whether the association of 53 SNPs with curve progression reported in Caucasian AIS are replicated in Japanese AIS.Summary of Background Data. Predicting curve progression is important in clinical practice of AIS. The progression of AIS is reported to be associated with a number of genes. Associations with 53 SNPs have been reported, and the SNPs are used for a progression test in Caucasian AIS; however, there has been no replication study for their association.Methods. We recruited 2,117 AIS patients with ≧ 10° (Cobb angle) of scoliosis curves. They were divided into progression and non-progression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle > 50° for skeletally mature subjects, > 40° for immature ones, and postoperative ones. We defined the non-progression of the curve as Cobb angle ≦50° only for skeletally mature subjects. 1,714 of 2,117 AIS patients were allocated to either the progression or non-progression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the two groups.Results. We evaluated the progression (N = 600) and non-progression (N = 1,114) subjects, and their risk allele frequencies were not different significantly. We found no replication of the association on AIS curve progression in any of the SNPs.Conclusion. The associations of the 53 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.
    Spine 04/2013; 38(16). DOI:10.1097/BRS.0b013e3182947d21 · 2.30 Impact Factor
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    ABSTRACT: To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence. (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. 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. 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 (> 25(o)); (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. This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.
    World journal of orthodontics 08/2015; 6(7):537-558. DOI:10.5312/wjo.v6.i7.537