Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).

Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

A Replication Study for the Association of rs11190870 With Curve Severity in Adolescent Idiopathic Scoliosis in Japanese.

STUDY DESIGN: Case-only study. OBJECTIVE: The aim of this study was to confirm the association of rs11190870 with adolescent idiopathic scoliosis (AIS) severity in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA: Although the association of rs11190870 with AIS susceptibility is replicated in multiple ethnics, the association of rs11190870 with curve severity is controversial. Since the previous studies are of small, we performed a replication study using far larger number of patients than previous studies. METHODS: A total of 1860 Japanese patients with AIS who had reached skeletal maturity or undergone surgical fusion were included in the study. We evaluated the association between rs11190870 and AIS progression for the entire group, and then for patients grouped according to a severe curve (a Cobb angle of ≥40°) or mild curve (a Cobb angle <30°). Because braces could affect the results of the present study, patients in the mild-curve group were divided according to whether or not they had worn a brace. We then evaluated associations between rs11190870 genotype and curve severity in these groups. RESULTS: The mean Cobb angles were 54.8°â€Š±â€Š12.1° in the severe-curve group and 24.4°â€Š±â€Š4.0° in the mild-curve group. The difference in rs11190870 risk-allele frequency between the severe- and mild-curve groups was evaluated. No significant differences were observed. We then examined the association of rs11190870 risk-allele frequency between patients in the mild- and severe-curve groups using the χ test for three models, and found a marginal association between rs11190870 and curve severity in the dominant model (P = 0.035, odds ratio = 1.51). CONCLUSION: We found no association between rs11190870 and curve severity using the criteria of previous study. However, we found a marginal association between rs11190870 and curve severity. Large-scale replication studies that consider skeletal maturity and brace history, including replication studies in other ethnic groups, would be helpful for clarifying the association. LEVEL OF EVIDENCE: 4.

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.

Minimum 20 Years Long-term Clinical Outcome After Spinal Fusion and Instrumentation for Scoliosis: Comparison of the SRS-22 Patient Questionnaire With That in Nonscoliosis Group.

STUDY DESIGN: A retrospective minimum 20-year follow-up study using 4 standard self-administered questionnaires, one of which, the SRS-22 was also administered to control groups. OBJECTIVE: To evaluate long-term postoperative pain and other clinical outcomes of scoliosis correction and fusion surgery with Harrington instrumentation using Moe square-ended rods for better preservation of sagittal alignment. SUMMARY OF BACKGROUND DATA: Only a few long-term outcome studies have used standardized and validated self-administered tools, and no studies have established SRS-22 control data within their own population. There is no previous minimum 20-year follow-up evaluation after correction surgery preserving thoracic kyphosis and lumbar lordosis. METHODS: Of 86 consecutive patients who underwent instrumentation surgery for scoliosis by a single surgeon, 61 patients participated using Japanese Orthopaedic Association, Roland-Morris Disability Questionnaire, Oswestry Disability Index, and Scoliosis Research Society (SRS-22) questionnaires and 51 patients were included in this study. Results were analyzed for pain and other clinical outcomes. A total of 771 hospital employees were sent SRS-22 questionnaires. A total of 763 responded, resulting in 2 control groups composed of nonscoliosis and untreated mild scoliosis controls of the same culture and language as the long-term follow-up group. RESULTS: The prevalence of continuous low back pain was about 15%. Average Japanese Orthopaedic Association, Oswestry Disability Index, and Roland-Morris Disability Questionnaire scores at follow-up were 25 points, 7.3%, and 1.6, respectively. The average SRS-22 scores were 4.2 (function), 4.3 (pain), 3.7 (self-image), and 3.9 (mental health) for the postoperative follow-up group compared with 4.5 (function), 4.3 (pain), 3.5 (self-image), and 3.5 (mental health) for the nonscoliosis controls. CONCLUSION: Improved preservation of normal sagittal alignment resulted in a prevalence of low back pain comparable with the age-matched general population. Moreover, SRS-22 results for self-image and mental health were positive compared with the controls, possibly reflecting the surgeon's emphases on mental health and management of patient expectations. LEVEL OF EVIDENCE: 4.

Significance of peak height velocity as a predictive factor for curve progression in patients with idiopathic scoliosis.

BACKGROUND: Much attention has been paid to peak height velocity (PHV) as a possible predictor of curve progression in patients with idiopathic scoliosis (IS). The aim of this study was to analyze the relationship between the magnitude of the Cobb angle at PHV and scoliosis progression, defined as having surgery prior to skeletal maturity in female patients with IS. METHODS: A retrospective review identified 56 skeletally immature female IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 10 years and 24 months before menarche respectively, with a follow-up period of 5 years. They were divided into two groups: non-surgery group (NS) and surgery group (S), depending on their treatment method in use at the final follow-up visit. Surgery group was defined as an ultimately having surgery due to Cobb angle greater than 45 degrees prior to skeletal maturity regardless of conservative management. Height measurements were recorded at each visit; height velocity was calculated as the height change, in cm, divided by the time interval, in years. The PHV, chronological age at PHV (APHV), height at PHV (HPHV), and final height (FH) were determined for each group. In patients with Cobb angle greater than 30 degrees, the corrected height was calculated by Kono formula and corrected height velocity values were provided. The sensitivity, specificity, and area under the curve (AUC) of the receiver-operating -characteristic (ROC) analysis were calculated to predict spinal curve progression for various Cobb-angle cutoff values at PHV. RESULTS: The corrected PHV had a mean value of 8.5 and 8.9 cm/year in the NS-group and S-group, respectively. The APHV was 11.9 and 11 years, the corrected HPHV was 152.9, and 149.3 cm, and the corrected FH was 159.9 and 159.3 cm, respectively. When a Cobb angle of 31.5 degrees was at PHV, ROC analysis revealed 78% sensitivity, 82% specificity, and an AUC of 0.93, acceptable values for curve progression in patients with IS. CONCLUSIONS: These findings indicate that 31.5 degrees of spinal curvature when patients are at PHV is a significant predictive indicator for progression of the curve to a magnitude requiring surgery. We suggest that the curve-progression risk assessment in patients with IS should include PHV, along with measures of skeletal and non-skeletal maturities.

Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.

A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese.

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 white patients with AIS are replicated in Japanese patients with 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 white patients with AIS; however, there has been no replication study for their association. METHODS: We recruited 2117 patients with AIS with 10° or more (Cobb angle) of scoliosis curves. They were divided into progression and nonprogression groups according to their Cobb angle. We defined the progression of the curve as Cobb angle more than 50° for skeletally mature subjects and more than 40° for immature patients, subjects. We defined the nonprogression of the curve as Cobb angle 50° or less only for skeletally mature subjects. Of the 2117 patients, 1714 patients with AIS were allocated to either the progression or nonprogression group. We evaluated the association of 53 SNPs with curve progression by comparing risk allele frequencies between the 2 groups. RESULTS: We evaluated the progression (N = 600) and nonprogression (N = 1114) subjects. 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. LEVEL OF EVIDENCE: N/A.

A replication study for association of 5 single nucleotide polymorphisms with curve progression of adolescent idiopathic scoliosis in Japanese patients.

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 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA: AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them. METHODS: We recruited 2117 patients with AIS with a Cobb angle of 10° or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40° or greater were included in the progression group, and those whose scoliotic curves were less than 30° and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype. RESULTS: We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION: The associations of the 5 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.

Height velocity curves in female patients with idiopathic scoliosis.

Following identification of peak height velocity (PHV) by a recent study as a possible prognostic factor for curve progression in patients with idiopathic scoliosis (IS), the aim of this study was to investigate PHV curves in Japanese female patients with IS. The study subjects were 20 skeletally immature IS patients who were followed until maturity. The mean age and the mean pubertal status at the initial visit were 9.8 years and 24 months before menarche, respectively, with a follow-up period of 5.2 years. Height measurements were recorded at each visit, and HV was calculated as the change in height (cm) divided by the time interval (yr.) between visits of 6 to 12 months. The PHV, age at PHV (APHV), height at PHV (HPHV), and final height (FH) were determined. Patient HV curves were plotted using their HV data, and growth periods (GPs) were calculated from the curves. PHVs and GPs of study patients were compared to standard data from unaffected girls. The median values and interquartile ranges in PHV, APHV, HPHV, and FH were 8.5 cm/yr. (7.9-9.7), 11.8 yr. (11.2-12.1), 153.2 cm (150.1-155.8), and 160.1 cm (157.4-162.4), respectively. The median GP was 27 months. The PHV and GP values in IS female patients were higher and shorter than those in unaffected girls. These findings indicate that the patterns of height velocity curves in IS patients are different from those in unaffected girls, suggesting that curve progression in IS patients is associated with the magnitude of PHV and duration of GP. Recently, we have developed an HV reader to easily and quickly identify the present HV in patients with scoliosis, applicable for the clinical setting or school screening. We conclude that risk assessments of curve progression in patients with IS should include HV along with measures of skeletal maturity such as the Risser sign and/or digital skeletal age using hand X-rays.

A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2-3% of school-age children worldwide(1). Genetic factors have been implicated in its etiology(2). Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 × 10(-19); odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis.

Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes.

Adolescent idiopathic scoliosis (AIS) is a common disorder with a strong genetic predisposition. Associations between AIS and common single nucleotide polymorphisms (SNPs) in estrogen receptor genes have been reported. rs9340799 in the gene for estrogen receptor α (ESR1) is reported to be associated with curve severity in Japanese and with AIS predisposition and curve severity in Chinese. In addition, rs1256120 in the gene for estrogen receptor ß (ESR2) is reported to be associated with AIS predisposition and curve severity in Chinese. However, the sample sizes of these previous studies were small, and the associations of these SNPs have not been replicated. To examine the association between AIS and estrogen receptor genes, we investigated the association of rs9340799 and rs1256120 with AIS predisposition and curve severity using a large Japanese population, consisting of 798 AIS patients and 637 sex-matched controls. We found no association of either SNP with AIS predisposition or curve severity in the Japanese population. Considering the statistical power of the present study and the limitations of the previous reports, we conclude that the associations of rs9340799 and rs1256120 with AIS predisposition and curve severity are negative.

Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population.

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin-like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR-based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese.

Super Hybrid Method of scoliosis correction: minimum 2-year follow-up.

We applied a new surgical technique utilizing conventional hybrid instrumentation to achieve better correction of trunk deformity in adolescent idiopathic scoliosis. The purpose of this study is to introduce our "Super Hybrid Method" and to analyze the results at minimum 2-year follow-up. The technique consists of rib mobilization (2006), a rod rotation maneuver (1997) and a hook rotation maneuver (2007). Forty-four idiopathic cases (female: 43) with minimum 2-year follow-up were reviewed (24-39 months, average 32). The average age at surgery was 20.4 years (12-57). The average pre-operative Cobb angle was 56.7 degrees (40-93). The average pre-operative rib hump was 23.2mm in height and 14.3 degrees by scoliometer. The average post-op Cobb angle was 13.3 degrees at 3 weeks and 18.1 degrees at follow-up. The average initial overall correction at 3 weeks post-op was 78% (83% for age<18, 73% for age < or =18) and 70% at later follow up (75% for age<18, 67% for age < or =18). The average rib hump 2 years post-operatively was 12.4mm in height and 7.3 degrees. Sixty nine percent of patients (18/26) with a pre-operative rib hump < or =20mm (20-49) had a decrease in hump height by more than 10mm (10-34). In Moiré analysis, the hump-sum measure (Suzuki) showed a statistically significant decrease from 13.4 preoperatively to 9.2 at 1 year post-op (p<0.001). Correction of deformity was excellent with our new technique. It is a less expensive procedure and carries little inherent risks.

Factors of thoracic cage deformity that affect pulmonary function in adolescent idiopathic thoracic scoliosis.

STUDY DESIGN: This clinical study examined the association between pulmonary function and thoracic cage deformities in scoliosis. OBJECTIVE: To determine the factors in spinal and thoracic cage deformities that affect pulmonary function in scoliosis. SUMMARY OF BACKGROUND DATA: Pulmonary function in scoliosis has generally been evaluated in terms of lateral spinal curvature. No previous report has evaluated changes in pulmonary function taking into consideration measurements reflecting not only spinal curvature but also thoracic cage deformities, although scoliosis is a three-dimensional deformity. METHODS: A total of 109 patients (mean age, 14.2 years) with adolescent idiopathic right thoracic scoliosis (mean lateral spinal curvature, 37.7 degrees) had full assessment of pulmonary function and a radiographic evaluation from radiographs of the whole spine, Moiré topography, and thoracic computed tomography. RESULTS: Multiple regression analysis (stepwise method) was performed at each vertebral level from T3-T12 to identify the factor that most strongly affects %VC. The correlation coefficient was highest at T9 and next highest at T8, with values of 0.641 (r2 = 0.411, P < 0.0001) and 0.625 (r2 = 0.390, P < 0.0001), respectively. At T9, multiple regression analysis showed that the sagittal diameter of the thoracic cage and the total lung area were identified as factors that most strongly affect %VC. Similarly, the sagittal diameter of the thoracic cage and the rotation angle to the sagittal plane were identified at T8. CONCLUSIONS: The factors that reduced %VC were the sagittal diameter of the thoracic cage, total lung area and vertebral rotation at the T8 and T9 levels.