Self-Experienced Trunk Appearance in Individuals With and Without Idiopathic Scoliosis.

STUDY DESIGN: Cross-sectional. OBJECTIVE: The aim of this study was to describe the self-experienced trunk appearance in individuals with and without idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Idiopathic scoliosis is the most common spinal deformity. A large scoliotic deformity increases the risk of back pain and pulmonary dysfunction. The deformity has also a psychological impact. METHODS: The pictorial part of the spinal appearance questionnaire (pSAQ) was administered to 1416 individuals with idiopathic scoliosis (386 untreated, 529 brace treated, 501 surgically treated) and 272 individuals without scoliosis from the general population. Comparisons were made between individuals with and without scoliosis, between treatment groups and sex in the scoliosis group. RESULTS: Mean (95% confidence interval) age of the individuals with scoliosis was 36.2 (35.5-36.9) years and for the individuals without scoliosis 40.2 (37.9-42.4). pSAQ total was 12.3 (12.1-12.5) for individuals with scoliosis and 7.4 (7.3-7.6) for individuals without scoliosis (P < 0.001, adjusted for age and sex). pSAQ total was 11.5 (11.1-11.9) for untreated, 13.0 (12.6-13.3) for brace treated, and 12.3 (11.9-12.6) for surgically treated individuals (P < 0.001, adjusted for sex and curve size). The pSAQ total between males and females with idiopathic scoliosis did not differ (P = 0.22 adjusted for age and curve size). CONCLUSION: This study shows that individuals with idiopathic scoliosis have more concern about their body appearance than individuals without scoliosis. Untreated individuals are not as bothered of their spinal appearance as treated individuals. Males and females with scoliosis do not differ significantly in the perception of their spinal appearance. LEVEL OF EVIDENCE: 3.

Back Pain and Quality of Life After Surgical Treatment for Adolescent Idiopathic Scoliosis at 5-Year Follow-up: Comparison with Healthy Controls and Patients with Untreated Idiopathic Scoliosis.

BACKGROUND: Posterior spinal fusion with pedicle screws is the gold-standard treatment for adolescent idiopathic scoliosis (AIS); however, it is unclear whether this procedure results in improved long-term back pain and health-related quality of life compared with patients not surgically treated for AIS. The aim of the present study was to evaluate back pain and quality of life in surgically managed patients with a minimum follow-up of 5 years compared with patients with untreated AIS and a healthy control group. METHODS: Fifty-five consecutive adolescent patients who underwent posterior pedicle screw instrumentation for AIS by a single orthopaedic surgeon were prospectively enrolled. At a minimum of 5 years postoperatively, 49 patients completed Scoliosis Research Society (SRS)-24 questionnaires, and data on reoperation were collected. Pain and quality-of-life parameters were compared with those of 49 age and sex-matched patients with untreated AIS and 49 healthy controls. RESULTS: The major curve averaged 53° preoperatively and 12° at 2 years postoperatively. One reoperation (pedicle screw removal) was needed because of a new neurological deficit (transient). The SRS-24 pain, function, and total scores improved significantly from preoperatively to 5 years postoperatively (all p ≤ 0.016), with pain scores improving from 4.0 to 4.3 (p = 0.003). There was no association between pain scores and the preoperative major curve, instrumentation below L1, or postoperative rib hump. The surgical treatment group had significantly better pain, activity, and self-image domain scores at 5 years postoperatively compared with the untreated AIS group (all p ≤ 0.014), and similar pain, self-image, and activity domain scores compared with the healthy control group; however, function scores were significantly lower among patients in the surgical treatment group (p < 0.001). CONCLUSIONS: Patients who underwent posterior spinal fusion with pedicle screws experienced improved back pain and health-related quality of life compared with patients with untreated AIS. Patients in the surgical treatment group had similar health-related quality of life to that of the healthy control group, except for function, which was significantly lower. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10-13; odds ratio = 1.36, 95% confidence interval = 1.25-1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.

Quality of Life in Males and Females With Idiopathic Scoliosis.

STUDY DESIGN: Cross-sectional. OBJECTIVE: To describe quality of life in males and females with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Idiopathic scoliosis is a three-dimensional deformity affecting the growing spine. The prevalence of larger curves, requiring treatment, is higher in females. METHODS: This cross-sectional study comprised 1519 individuals with idiopathic scoliosis (211 males) with a mean (SD) age of 35.3 (14.9) years. They all answered the Scoliosis Research Society 22 revised (SRS-22r) questionnaire and EuroQol 5-dimension-index (EQ-5D). Five hundred twenty eight were surgically treated (78 males), 535 were brace treated (50 males), and 456 were untreated (83 males). The SRS-22r subscore (excluding the satisfaction domain), the SRS-22r domains and the EQ-5D index score were calculated. Subgroup analyses based on treatment and age were performed. Statistical comparisons were performed using analysis of covariance with adjustments for age and treatment. A P-value less than 0.05 was considered as statistical significant. RESULTS: The mean (SD) SRS-22r subscore was 4.19 (0.61) in males and 4.05 (0.61) in females (P = 0.010). The males had higher scores on the SRS-22r domains function (4.56 vs. 4.42), pain (4.20 vs. 4.00), and mental health (4.14 vs. 3.92) (all P < 0.05). The mean (SD) EQ-5D index score was 0.85 (0.22) for males and 0.81 (0.21) for females (P = 0.10). There were minor differences when comparing males and females in treatment and age groups, but both treated and untreated groups had reduced quality of life compared with the national norms. CONCLUSION: When compared with females, males with idiopathic scoliosis tend to have slightly higher scores in the scoliosis specific SRS-22r but not in the generic quality of life measurement EQ-5D. Quality of life is overall similar between males and females in treatment and age groups, but reduced in comparison with the general population. LEVEL OF EVIDENCE: 3.

Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.

Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.

A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10-20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

Health-Related Quality of Life in Adulthood in Untreated and Treated Individuals with Adolescent or Juvenile Idiopathic Scoliosis.

BACKGROUND: Health-related quality of life in adults with idiopathic scoliosis diagnosed before maturity has been reported to be similar between brace-treated and surgically treated individuals. The aim of this study was to compare health-related quality of life in untreated, brace-treated, and surgically treated adults with idiopathic scoliosis diagnosed before skeletal maturity. Subgroup analyses were performed on the basis of age at the time of the study, age of onset, surgical characteristics, and curve magnitude. METHODS: We included 1,187 adults with juvenile or adolescent idiopathic scoliosis with a mean age (and standard deviation) of 38.8 ±12.7 years. Of these, 347 were untreated, 459 had been brace-treated, and 381 had been surgically treated. The Scoliosis Research Society-22r (SRS-22r) and EuroQol 5-Dimensions (EQ-5D) were used. Statistical analyses were performed using analysis of covariance. RESULTS: The mean SRS-22r subscore was 4.15 ± 0.59 points for the untreated group, 4.10 ± 0.57 points for the previously braced group, and 4.01 ± 0.64 points for the surgically treated group (p = 0.007 adjusted for age and sex). The EQ-5D index was 0.82 ± 0.20 for the untreated group, 0.82 ± 0.20 for the previously brace-treated group, and 0.79 ± 0.24 for the surgically treated group (p = 0.026, adjusted for age and sex). Brace cessation was at the mean age of 16.2 ± 1.5 years, and the surgical procedure had been performed at the mean age of 15.3 ± 2.1 years. A more caudal fusion was associated with a lower SRS-22r subscore and EQ-5D index. No differences were observed when comparing individuals with juvenile or adolescent onset scoliosis (all p > 0.05). CONCLUSIONS: Untreated adults with idiopathic scoliosis had similar health-related quality of life to previously brace-treated individuals, and they had marginally higher health-related quality of life compared with surgically treated individuals. Therefore, both surgical and brace treatments for idiopathic scoliosis could be considered successful from a health-related quality-of-life point of view in adulthood. The age of onset of idiopathic scoliosis does not seem to influence quality of life in adulthood. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.

Neck and back problems in adults with idiopathic scoliosis diagnosed in youth: an observational study of prevalence, change over a mean four year time period and comparison with a control group.

BACKGROUND: The knowledge is sparse concerning neck problems in patients with idiopathic scoliosis. This is an observational study including a control group which aims to describe the prevalence of neck problems and the association with back problems among adult individuals with and without idiopathic scoliosis. METHODS: One thousand sixty-nine adults with a mean age of 40 years, diagnosed with idiopathic scoliosis in youth, answered a questionnaire on neck and back problems. Eight hundred seventy of these answered the same questionnaire at a second occasion in a mean of 4 years later. Comparisons were made with a cross-sectional population-based survey of 158 individuals. Statistical analyses were made with logistic regression or analysis of variance, adjusted for age, smoking status, and sex. RESULTS: Individuals with scoliosis were previously untreated (n = 374), brace treated (n = 451), or surgically treated (n = 244). Of the individuals with scoliosis, 42% (n = 444) had neck problems compared to 20% (n = 32) of the controls (p = 0.001). The prevalence of neck problems was not affected by the type of treatment (p = 0.67) or onset of scoliosis; juvenile (n = 159) or adolescent (n = 910; p = 0.68). Neck and/or back problems were experienced by 72% of the individuals with scoliosis and 37% of the controls (p < 0.001). Of the individuals with scoliosis having neck problems, 81% also reported back problems, compared to 59% of the individuals in the control group (p < 0.001). The prevalence of neck and back problems was similar at the second survey. CONCLUSIONS: Neck problems are more prevalent and more often coexist with back problems in individuals with idiopathic scoliosis than in controls. The majority of individuals have persisting problems over time.

An observational study on surgically treated adult idiopathic scoliosis patients' quality of life outcomes at 1- and 2-year follow-ups and comparison to controls.

BACKGROUND: Prospective data on health-related quality of life in patients with idiopathic scoliosis treated surgically as adults is needed. We compared preoperative and 1- and 2-year follow-up data in surgically treated adults with idiopathic scoliosis with juvenile or adolescent onset. Results were compared to untreated adults with scoliosis and population normative data. METHODS: A comparison of preoperative and 1- and 2-year follow-up data of 75 adults surgically treated for idiopathic scoliosis at a mean age of 28 years (range 18 to 69) from a prospective national register study, as well as a comparison with age- and sex-matched data from 75 untreated adults with less severe scoliosis and 75 adults without scoliosis, was made. Outcome measures were EuroQol-5 dimensions (EQ-5D) and Scoliosis Research Society (SRS)-22r questionnaire. RESULTS: In the surgically treated, EQ-5D and SRS-22r scores had statistically significant improvements at both 1- and 2-year follow-ups (all p < 0.015). The effect size of surgery on EQ-5D at 1-year follow-up was large (r = -0.54) and small-medium (r = -0.20) at 2-year follow-up. The effect size of surgery on SRS-22r outcomes was medium-large at 1- and 2-year follow-ups (r = -0.43 and r = -0.42 respectively). At the 2-year follow-up, the EQ-5D score and the SRS-22r subscore were similar to the untreated scoliosis group (p = 0.56 and p = 0.91 respectively), but lower than those in the adults without scoliosis (p < 0.001 for both comparisons). CONCLUSIONS: Adults with idiopathic scoliosis experience an increase in health-related quality of life following surgery at 2-year follow-up, approaching the health-related quality of life of untreated individuals with less severe scoliosis, but remain lower than normative population data.

Population-based normative data for the Scoliosis Research Society 22r questionnaire in adolescents and adults, including a comparison with EQ-5D.

PURPOSE: The Scoliosis Research Society (SRS) 22r questionnaire is a widely used instrument. To estimate the disorder´s impact on quality of life and to gain knowledge about treatment effects, normative values are needed. METHODS: Individuals were randomly invited from the general population. 272 individuals (145 females) answered the SRS-22r and EuroQol 5-dimensions (EQ-5D) questionnaires and stratified according to sex and age; ≤19 years (n = 61), 20-39 years (n = 66), 40-59 years (n = 84) and ≥60 years (n = 61). The correlation between SRS-22r and EQ-5D were analyzed. RESULTS: There were modest variations in mean SRS-22r scores (ranging between 4.3 and 4.7). EQ-5D followed the same pattern. The correlation between the SRS-22r was 0.62 (p = 0.001) and 0.61 (p < 0.001) for the EQ-5D UK tariff and EQ-5D Swedish tariff, respectively. CONCLUSION: We provide the first SRS-22r normative data for adolescents and adults overall. We found a good correlation between SRS-22r and EQ-5D in individuals without spinal deformity.

Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical Activity and Fracture Rate as Controls.

STUDY DESIGN: Cross-sectional. OBJECTIVE: To describe physical activity level and fracture rates in adults with idiopathic scoliosis, diagnosed before maturity, and to compare with a control group. SUMMARY OF BACKGROUND DATA: A previous study found a lower level of sporting activities in adults treated for idiopathic scoliosis compared with controls. Other studies have shown a lower bone mass in adults with idiopathic scoliosis compared with controls. METHODS: One thousand two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and 214 controls (aged 18-70 yr) were included and answered the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about previous fractures. The three scoliosis treatment groups (untreated n = 360, brace n = 460, and surgically treated n = 458) were compared. Furthermore, a comparison based on onset (juvenile n = 169 or adolescent n = 976) was performed. Achieved weekly moderate activity level and metabolic equivalent task (MET) minutes/week were assessed for patients and controls. Statistical comparisons were made with analysis of covariance with adjustments for age, body mass index, and sex. RESULTS: The proportion achieving weekly moderate activity level was 962 out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214 (73%) for controls (P = 0.40). The scoliosis patients reported 2016 MET-minutes/week (median value) and the controls 2456 (P = 0.06). Fracture rates did not differ (P = 0.72). Fewer surgically treated individuals achieved moderate activity level (P = 0.046) compared with the untreated and the previously braced individuals. No difference was seen regarding MET-minutes/week (P = 0.86). No differences were seen between individuals with a juvenile onset compared with individuals with an adolescent onset (all P ≥ 0.05). CONCLUSION: Adults with idiopathic scoliosis have similar physical activity level and do not sustain more fractures compared with controls. Adults with surgically treated idiopathic scoliosis have slightly lower physical activity level than previously braced and untreated patients. Onset of idiopathic scoliosis does not affect physical activity level. LEVEL OF EVIDENCE: 2.

Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples.

High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies.

Adolescents with and without idiopathic scoliosis have similar self-reported level of physical activity: a cross-sectional study.

BACKGROUND: Little is known about physical activity levels in individuals with idiopathic scoliosis. The aim of this study was to describe the level of physical activity in adolescents with and without idiopathic scoliosis. METHODS: Two hundred thirty-nine adolescents, median (25th, 75th percentile) age 16.0 (14.4, 17.6) with idiopathic scoliosis and 58 randomly recruited population-based individuals without scoliosis aged 14.6 (12.8, 16.3) participated. The 239 idiopathic scoliosis patients consisted of 88 untreated, 43 previously braced, 36 with ongoing brace-treatment and 72 surgically treated individuals. Main outcome measure was the proportion achieving at least moderate activity level, as estimated by the International Physical Activity Questionnaire short form (IPAQ-SF). Other outcome measures were Metabolic Equivalent Task (MET) minutes/week, time spent sitting, spare time activity level and sporting activities. Statistical analyses were adjusted for age and sex. RESULTS: The proportion of individuals with scoliosis with moderate activity level was 180 out of 239 (75 %) and for individuals without scoliosis 49 out of 58 (85 %) (p = 0.14). Median MET-minutes/week (25th,75th percentile) was for individuals with scoliosis scoliosis 1977 (840,3777) and for individuals without scoliosis 2120 (887,4598) (p = 0.11). Sporting activities did not differ (p = 0.28). The ongoing brace-treatment group had a significantly higher proportion of individuals categorizing themselves at high spare time activity level compared to the surgically treated and previously braced individuals (p = 0.046). No difference was seen between the treatment groups regarding the proportion achieving moderate activity (p = 0.11) and sporting activities (p = 0.20). Median MET minutes/week was 2160 (794,3797) for the untreated group, 989 (661,2706) for the previously braced group, 2055 (1010, 4026) for the surgery group and 2106 (990,4480) for the ongoing brace-treatment group (p = 0.031). CONCLUSION: Adolescents with idiopathic scoliosis show similar levels of self-reported physical activity as individuals without idiopathic scoliosis. Bracing and surgery do not appear to inhibit physical activity.

Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis.

BACKGROUND CONTEXT: Idiopathic scoliosis is a spinal deformity affecting approximately 3% of otherwise healthy children or adolescents. The etiology is still largely unknown but has an important genetic component. Genome-wide association studies have identified a number of common genetic variants that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding. PURPOSE: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants. STUDY DESIGN: This was a case control study. PATIENT SAMPLE: A total of 1,739 patients with idiopathic scoliosis and 1,812 controls were included. OUTCOME MEASURE: The outcome measure was idiopathic scoliosis. METHODS: The variants rs10510181, rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5'UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing, were Sanger sequenced in the 100 pooled samples. RESULTS: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10(-18)). We identified 20 novel variants by exome sequencing after filtration and an initial genotyping validation. However, we could not verify any association to idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. We did not find any variants in the 5'UTR, noncoding exon and promoter regions of LBX1. CONCLUSIONS: Here, we confirm LBX1 as a susceptibility gene for idiopathic scoliosis in a Scandinavian population and report that we are unable to find evidence of other genes of similar or stronger effect.

An observational study on the outcome after surgery for lumbar disc herniation in adolescents compared with adults based on the Swedish Spine Register.

BACKGROUND CONTEXT: Disc-related sciatica has a prevalence of about 2% in adults, but is rare in adolescents. If conservative treatment is unsuccessful, surgery is an option. PURPOSE: The aim of this study was to compare the outcomes of surgery for lumbar disc herniation in adolescents with adults in the Swedish Spine Register. STUDY DESIGN/SETTING: This is a prospective observational study: National Quality Register. PATIENT SAMPLE: This study included 151 patients, 18 years or younger, 4,386 patients, 19-39 years, and 6,078 patients, 40 years or older, followed for 1-2 years after surgery. OUTCOME MEASURES: The primary outcomes were patient satisfaction and global assessment of leg and back pain. Secondary outcomes were Visual Analog Scale (VAS) leg pain, VAS back pain, Oswestry disability index (ODI), and EuroQol-5 dimensions (EQ-5D). METHODS: Statistical analyses were performed with the Welch F test, the chi-square test, and the Wilcoxon signed-rank test. RESULTS: At follow-up, 86% of the adolescents were satisfied compared with 78% in the younger adults and 76% in the older adults group (p<.001). According to the global assessment, significantly decreased leg pain was experienced by 87% of the adolescents, 78% of the younger adults, and 71% of the older adults (p<.001). Corresponding figures for back pain were 88%, 73%, and 70%, respectively (p<.001). All groups experienced significant postoperative improvement of VAS leg pain, VAS back pain, ODI, and EQ-5D (all p<.001). CONCLUSIONS: The adolescent age group was more satisfied with the treatment than the adult groups. There was a significant improvement in all age groups after surgery.

Prevalence of Back Problems in 1069 Adults With Idiopathic Scoliosis and 158 Adults Without Scoliosis.

STUDY DESIGN: Multicenter case-control study. OBJECTIVE: To investigate the prevalence of back problems in adults with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Information on the prevalence of back problems in adults with idiopathic scoliosis is scarce, especially in untreated individuals, males, and individuals with an age at the onset of scoliosis of less than 10 years. METHODS: A total of 1069 individuals with idiopathic scoliosis and 158 individuals without scoliosis, all aged 20 to 65 years, answered a questionnaire on back problems. Individuals with scoliosis were diagnosed between ages 4 and 20 years and any treatment was terminated before the age of 20 years. Logistic regression or analysis of variance was used for group comparisons. RESULTS: Mean (SD) age at the time of investigation in individuals with scoliosis (123 males and 946 females) was 41 (9) years, and in individuals without scoliosis (75 males and 83 females) 45 (13) years. Three hundred seventy-four individuals with scoliosis were untreated, 451 had been brace treated, and 244 were surgically treated. The mean prevalence of back problems was 64% in the individuals with scoliosis and 29% in the individuals without scoliosis (P < 0.001). Among the untreated individuals with scoliosis, 69% reported back problems; among the brace treated, 61%; and among the surgically treated, 64% (P = 0.06). When comparing females and males with scoliosis, and individuals with juvenile and adolescent scoliosis, there were no statistically significant differences in the prevalence of back problems (P = 0.10 and P = 0.23, respectively). CONCLUSION: Adults with idiopathic scoliosis have a higher prevalence of back problems than individuals without scoliosis. Treatment, sex, and juvenile or adolescent onset of diagnosis was not related to the prevalence of back problems in adulthood. LEVEL OF EVIDENCE: 2.

Family history and its association to curve size and treatment in 1,463 patients with idiopathic scoliosis.

PURPOSE: To study family history in relation to curve severity, gender, age at diagnosis and treatment in idiopathic scoliosis. METHODS: A self-assessment questionnaire on family history of scoliosis was administered to 1,463 untreated, brace or surgically treated idiopathic scoliosis patients. RESULTS: Out of the 1,463 patients, 51 % had one or more relatives with scoliosis. There was no significant difference between females and males, nor between juvenile and adolescent study participants in this respect (p = 0.939 and 0.110, respectively). There was a significant difference in maximum curve size between patients with one or more relatives with scoliosis (median 35°, interquartile range 25) and patients without any relative with scoliosis (median 32°, interquartile range 23) (p = 0.022). When stratifying patients according to treatment (observation, brace treatment or surgery), we found that it was more common to have a relative with scoliosis among the treated patients (p = 0.011). The OR for being treated was 1.32 (95% CI 1.06-1.64) when the patient had a relative with scoliosis, compared to not having. CONCLUSIONS: Larger curve sizes were found in patients with a family history of scoliosis than in the ones without. No relation between family history and gender or between family history and age at onset of idiopathic scoliosis was found. Although the presence of a family history of scoliosis may not be a strong prognostic risk factor, it indicates that these patients are at higher risk of developing a more severe curve.

Heritability of scoliosis.

PURPOSE: To estimate the heritability of scoliosis in the Swedish Twin Registry. METHODS: Self-reported data on scoliosis from 64,578 twins in the Swedish Twin Registry were analysed. Prevalence, pair- and probandwise concordances and tetrachoric correlations in mono- and dizygotic same-sex twins were calculated. The relative importance of genetic variance, i.e. the heritability, and unique and shared environmental variance was estimated using structural equation modelling in Mx software. In addition, all twins in the twin registry were matched against the Swedish Inpatient Register on the primary diagnosis idiopathic scoliosis. RESULTS: The prevalence of scoliosis was 4%. Pair- and probandwise concordance was 0.11/0.17 for mono- and 0.04/0.08 for same-sex dizygotic twins. The tetrachoric correlation (95% CI) was 0.41 (0.33-0.49) in mono- and 0.18 (0.09-0.29) in dizygotic twins. The most favourable model in the Mx analyses estimated the additive genetic effects (95% CI) to 0.38 (0.18-0.46) and the unique environmental effects to 0.62 (0.54-0.70). Shared environmental effects were not significant. The pairwise/probandwise concordance for idiopathic scoliosis in the Swedish Inpatient Register was 0.08/0.15 for monozygotic and zero/zero for same-sex dizygotic twins. CONCLUSION: Using self-reported data on scoliosis from the Swedish Twin Registry, we estimate that 38% of the variance in the liability to develop scoliosis is due to additive genetic effects and 62% to unique environmental effects. This is the first study of sufficient size to make heritability estimates of scoliosis.