Three-dimensional pelvic incidence is much higher in (thoraco)lumbar scoliosis than in controls.

PURPOSE: The pelvic incidence (PI) is used to describe the sagittal spino-pelvic alignment. In previous studies, radiographs were used, leading to less accuracy in establishing the three-dimensional (3D) spino-pelvic parameters. The purpose of this study is to analyze the differences in the 3D sagittal spino-pelvic alignment in adolescent idiopathic scoliosis (AIS) subjects and non-scoliotic controls. METHODS: Thirty-seven female AIS patients that underwent preoperative supine low-dose computed tomography imaging of the spine, hips and pelvis as part of their general workup were included and compared to 44 non-scoliotic age-matched female controls. A previously validated computerized method was used to measure the PI in 3D, as the angle between the line orthogonal to the inclination of the sacral endplate and the line connecting the center of the sacral endplate with the hip axis. RESULTS: The PI was on average 46.8° ± 12.4° in AIS patients and 41.3° ± 11.4° in controls (p = 0.025), with a higher PI in Lenke type 5 curves (50.6° ± 16.2°) as compared to controls (p = 0.042), whereas the Lenke type 1 curves (45.9° ± 12.2°) did not differ from controls (p = 0.141). CONCLUSION: Lenke type 5 curves show a significantly higher PI than controls, whereas the Lenke type 1 curves did not differ from controls. This suggests a role of pelvic morphology and spino-pelvic alignment in the pathogenesis of idiopathic scoliosis. Further longitudinal studies should explore the exact role of the PI in the initiation and progression of different AIS types. These slides can be retrieved under Electronic Supplementary Material.

Titanium granules pre-treated with hydrogen peroxide inhibit growth of bacteria associated with post-operative infections in spine surgery.

PURPOSE: Post-operative infections are relatively common after posterior spine surgery, and there are several observations reflecting different infection complications related to various metals implanted. Here, we selected an array of different bacterial species that are often found in infections associated with orthopaedic implants and tested for inhibition by hydrogen peroxide-treated titanium (Ti-peroxy). METHODS: To study the possibility of using Ti-peroxy as an antimicrobial prophylaxis, we developed a protocol for standardized susceptibility testing of bacteria. RESULTS: Importantly, we found that the resulting Ti-peroxy was highly antimicrobial against all aerobic species tested, among others, Staphylococcus aureus and Pseudomonas aeruginosa. Proteus mirabilis was slightly more resistant than, for example, Klebsiella pneumoniae and enterococci. In contrast, anaerobic bacteria Cutibacterium acnes and Parvimonas micra were equally susceptible compared to staphylococci. CONCLUSIONS: Our findings suggest that the Ti-peroxy is a promising perioperative antimicrobial strategy that may be highly effective for prevention of post-operative infections. We therefore suggest application of hydrogen peroxide to implants prior to implantation. These slides can be retrieved under Electronic supplementary material.

Nighttime Bracing or Exercise in Moderate-Grade Adolescent Idiopathic Scoliosis: A Randomized Clinical Trial.

Importance: Moderate-grade adolescent idiopathic scoliosis (AIS) may be treated with full-time bracing. For patients who reject full-time bracing, the effects of alternative, conservative interventions are unknown. Objective: To determine whether self-mediated physical activity combined with either nighttime bracing (NB) or scoliosis-specific exercise (SSE) is superior to a control of physical activity alone (PA) in preventing Cobb angle progression in moderate-grade AIS. Design, Setting, and Participants: The Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS) randomized clinical trial was conducted from January 10, 2013, through October 23, 2018, in 6 public hospitals across Sweden. Male and female children and adolescents aged 9 to 17 years with an AIS primary curve Cobb angle of 25° to 40°, apex T7 or caudal, and skeletal immaturity based on estimated remaining growth of at least 1 year were included in the study. Dates of analysis were from October 25, 2021, to January 28, 2023. Interventions: Interventions included self-mediated physical activity in combination with either NB or SSE or PA (control). Patients with treatment failure were given the option to transition to a full-time brace until skeletal maturity. Main Outcomes and Measures: The primary outcome was curve progression of 6° or less (treatment success) or curve progression of more than 6° (treatment failure) seen on 2 consecutive posteroanterior standing radiographs compared with the inclusion radiograph before skeletal maturity. A secondary outcome of curve progression was the number of patients undergoing surgery up until 2 years after the primary outcome. Results: The CONTRAIS study included 135 patients (45 in each of the 3 groups) with a mean (SD) age of 12.7 (1.4) years; 111 (82%) were female. Treatment success was seen in 34 of 45 patients (76%) in the NB group and in 24 of 45 patients (53%) in the PA group (odds ratio [OR], 2.7; 95% CI, 1.1-6.6). The number needed to treat to prevent curve progression with NB was 4.5 (95% CI, 2.4-33.5). Treatment success occurred in 26 of 45 patients (58%) in the SSE group (OR for SE vs PA, 1.2; 95% CI, 0.5-2.8). Up to 2 years after the primary outcome time point, 9 patients in each of the 3 groups underwent surgery. Conclusions and Relevance: In this randomized clinical trial, treatment with NB prevented curve progression of more than 6° to a significantly higher extent than did PA, while SSE did not; in addition, allowing transition to full-time bracing after treatment failure resulted in similar surgical frequencies independent of initial treatment. These results suggest that NB may be an effective alternative intervention in patients rejecting full-time bracing. Trial Registration: ClinicalTrials.gov Identifier: NCT01761305.

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.

Vertebral Hemangiomas: Prevalence, new classification and natural history. magnetic resonance imaging-based retrospective longitudinal study.

BACKGROUND AND PURPOSE: To determine the prevalence of vertebral hemangiomas (VHs), establish a new classification of VHs based on their MRI-signal pattern, and study their natural history. METHODS: MRI of 1000 consecutive patients who underwent at least two MRI with an interval of at least 3 years. Growth rate and change of MRI-signal pattern during the follow-up period were the parameters included in studying the natural history of VHs. RESULTS: The prevalence of VHs was 41%. VHs were classified as type I-IV with fat-rich VHs (type I), constituted 79% of all VHs. VHs were more common among females 43% versus males 39%, p = .22. The most affected vertebra was L1. Occurrence rates for cervical (1%), thoracic (7%), and lumbar spine (10%) differed significantly (p < .001). The prevalence of VHs increased with age regardless of gender or spinal part involved (p < .001). Only 26% of VHs changed their size and 4% changed their signal during the average follow-up of 7 years. All VHs were slowly growing lesions (average expected growth of <3 mm/10 years). No significant difference between growth rate of VHs type I (0.25 mm/year) and other types of VHs. None of the VHs that were initially reported as "metastases cannot be rule out" showed alarming change in signal or size. CONCLUSIONS: VH can be classified into four types based on their MRI-signal pattern. Regardless of their type, VHs are slowly growing lesions. The presence of typical morphological pattern should enable radiologists to confidently differentiate them from vertebral metastases.

Patients with adolescent idiopathic scoliosis of Lenke type-1 curve exhibit specific pedicle width pattern.

INTRODUCTION: Study aim was to find out if patients with Lenke type 1 curve exhibit smaller pedicles and specific pedicle width pattern compared with individuals with no scoliosis. MATERIALS AND METHODS: 4,828 pedicle width measurements (T1-L5) in 61 consecutive patients with adolescent idiopathic scoliosis of Lenke type 1 curve, 61 control subjects, and 20 patients with Lenke type 5 curve, were retrospectively performed by an experienced neuroradiologist. RESULTS: Among patients with Lenke type 1 curve, the differences between the width of right and left upper thoracic pedicles were statistically significant; smallest at right T4 (2.6 mm). At scoliotic apex, the pedicles on the concave (left) side were significantly smaller than those on the convex (right) side; smallest at left T7 (3.2 mm). Among patients with Lenke type 1 curve, 97% had pedicle width <4 mm. CONCLUSIONS: Our study showed that patients with Lenke type 1 curve exhibit smaller pedicles and asymmetric pedicle width compared with control subjects.

Spinal epidural lipomatosis: a common imaging feature in Scheuermann disease.

STUDY DESIGN: Retrospective study. OBJECTIVES: To find out if spinal epidural lipomatosis (SEL) occurs more commonly among patients with Scheuermann disease than in the general population. SUMMARY AND BACKGROUND: On the basis of our own radiologic and operative observation, SEL seems to occur frequently in patients with Scheuermann disease. METHODS: Magnetic resonance imaging of 87 individuals (72% male, average age 19±6 y) from 2 centers (29 consecutive patients with Scheuermann disease and 58 controls) were retrospectively evaluated by 2 neuroradiologists. Spinal epidural fat (EF) at seventh thoracic vertebra (EF7), maximum EF (EFmax), dural sac diameter at T7 and at the level of maximum EF (DS7 and DSmax) were measured. EF ratios at T7 (EFR7) and at maximum EF (EFRmax) were calculated as EF/DS. Body mass index (BMI) for study population and kyphosis severity for the patients were recorded. Mann-Whitney, Spearman correlation, and χ tests were performed dependent on the variable in question. RESULTS: EF7, DS7, EFmax, EFR7, and EFRmax was significantly higher among patients with Scheuermann disease (EFmax 5.7±2.4 mm) than among controls (EFmax 3.8±1.1 mm), P<0.001. Twelve patients with Scheuermann disease (41%) fulfilled our proposed criteria for the diagnosis of SEL (EFmax>6 mm+EFRmax>0.51) compared with 2 (3%) among controls (P<0.001). Patients with Scheuermann disease exhibited higher BMI than controls (24.9±5 kg/m vs. 22.9±4 kg/m, P=0.138). Logistic regression showed that the occurrence of SEL among patients with Scheuermann disease was independent of BMI (P=0.880). The degree of kyphosis in patients with Scheuermann's disease (62±20°) was correlated to the amount of the EF. CONCLUSIONS: As SEL occurs more frequently among patients with Scheuermann disease, spine magnetic resonance imaging should be routinely performed to screen each of these patients to avoid impending neurological injury during surgery, especially in those exhibiting SEL.

Optimization of radiation exposure and image quality of the cone-beam O-arm intraoperative imaging system in spinal surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: To optimize the radiation doses and image quality for the cone-beam O-arm surgical imaging system in spinal surgery. SUMMARY OF BACKGROUND: Neurovascular compromise has been reported after screw misplacement during thoracic pedicle screw insertion. The use of O-arm with or without navigation system during spinal surgery has been shown to lower the rate of screw misplacement. The main drawback of such imaging surgical systems is the high radiation exposure. METHODS: Chest phantom and cadaveric pig spine were examined on the O-arm with different scan settings: 2 were recommended by the O-arm manufacturer (120 kV/320 mAs, and 120 kV/128 mAs), and 3 low-dose settings (80 kV/80 mAs, 80 kV/40 mAs, and 60 kV/40 mAs). The radiation doses were estimated by Monte Carlo calculations. Objective evaluation of image quality included interobserver agreement in the measurement of pedicular width in chest phantom and assessment of screw placement in cadaveric pig spine. RESULTS: The effective dose/cm for 120 kV/320 mAs scan was 13, 26, and 69 times higher than those delivered with 80 kV/80 mAs, 80 kV/40 mAs, and 60 kV/40 mAs scans, respectively. Images with 60 kV/40 mAs were unreliable. Images with 80 kV/80 mAs were considered reliable with good interobserver agreement when measuring the pedicular width (random error 0.38 mm and intraclass correlation coefficient 0.979) and almost perfect agreement when evaluating the screw placement (κ value 0.86). CONCLUSIONS: The radiation doses of the O-arm system can be reduced 5 to 13 times without negative impact on image quality with regard to information required for spinal surgery.

The rate of screw misplacement in segmental pedicle screw fixation in adolescent idiopathic scoliosis.

BACKGROUND AND PURPOSE: There are no reports in the literature on the influence of learning on the pedicle screw insertion. We studied the effect of learning on the rate of screw misplacement in patients with adolescent idiopathic scoliosis treated with segmental pedicle screw fixation. METHOD: We retrospectively evaluated low-dose spine computed tomography of 116 consecutive patients (aged 16 (12-24) years, 94 females) who were operated during 4 periods over 2005-2009 (group 1: patients operated autumn 2005-2006; group 2: 2007; group 3: 2008; and group 4: 2009). 5 types of misplacement were recorded: medial cortical perforation, lateral cortical perforation, anterior cortical perforation of the vertebral body, endplate perforation, and perforation of the neural foramen. RESULTS: 2,201 pedicle screws were evaluated, with an average of 19 screws per patient. The rate of screw misplacement for the whole study was 14%. The rate of lateral and medial cortical perforation was 7% and 5%. There was an inverse correlation between the occurrence of misplacement and the patient number, i.e. the date of operation (r = -0.35; p < 0.001). The skillfulness of screw insertion improved with reduction of the rate of screw misplacement from 20% in 2005-2006 to 11% in 2009, with a breakpoint at the end of the first study period (34 patients). INTERPRETATION: We found a substantial learning curve; cumulative experience may have contributed to continued reduction of misplacement rate.

Dural ectasia in adolescent idiopathic scoliosis: quantitative assessment on magnetic resonance imaging.

To our knowledge, the assessment of dural sac diameters in patients with adolescent idiopathic scoliosis (AIS) is not reported in the literature. The aim of this study was to find out if, dural ectasia occurs more frequently among patients with AIS, to define cut-off values for dural sac ratio and test the validity of such values. A total of 126 spine MRIs (79 patients with AIS and 47 control subjects) were included in this retrospective analysis (age range 7-25 years, 62% were females). Dural sac diameter (DSD) and vertebral body diameter (VBD) were estimated and dural sac ratio (DSR = DSD/VBD) was calculated at T5 and L3. DSR at T5 and L3 were 0.69 +/- 0.12, and 0.52 +/- 0.10, respectively, in patients with AIS compared with 0.62 +/- 0.11, and 0.44 +/- 0.07, respectively, in controls (P = 0.001 at T5 and <0.001 at L3). Our estimated cut-off values for DSR were 0.84 and 0.58 at T5 and L3, respectively. This resulted in 100% sensitivity compared with 74% when using the cut-off values proposed by Oosterhof et al. No statistically significant association was found between the occurrence of dural sac enlargement in patients with AIS and the severity of scoliotic deformity, the apical vertebral rotation, epidural fat thickness, occurrence of pain, neurological deficit, atypical scoliosis or rapid curve progression. Females were affected more frequently than males. As dural sac enlargement means thinning of the pedicles, we believe that the findings of this study have important clinical implications on the preoperative workup of AIS.

Radiological and clinical outcome of screw placement in adolescent idiopathic scoliosis: evaluation with low-dose computed tomography.

Posterior corrective surgery using "all pedicle screw construct" carries risk of neurovascular complications. The study aims were to assess the screw placement in patients with adolescent idiopathic scoliosis using CT with low-radiation dose, and to evaluate the clinical outcome in patients with misplaced pedicle screws. CTs of 49 consecutive patients (873 screws, 79% thoracic) were retrospectively evaluated by two independent radiologists. A new grading system was developed to distinguish between lateral, medial and anterior cortical perforations, endplate perforation and foraminal perforation. The grading system is based on whether the cortical violation is partial or total rather than on mm-basis. The overall rate of screw misplacement was 17% (n = 149): 8% were laterally placed and 6.1% were medially placed. The rates of anterior cortical, endplate and foraminal perforation were 1.5, 0.9, and 0.5%, respectively. Lateral cortical perforation was more frequent in the thoracic spine (P = 0.005), whereas other types of misplacement including medial cortical perforation were more frequent on the left and the concave side of scoliotic curves (P = 0.002 and 0.003). No neurovascular complications were reported. The association between the occurrence of screw misplacement and the Cobb angle was statistically significant (P = 0.037). Misplacements exceeding half screw diameter should be classified as unacceptable. Low-dose CT implies exposing these young individuals to a significantly lower radiation dose than do other protocols used in daily clinical practice. We recommend using low-dose CT and the grading system proposed here in the postoperative assessment of screw placement.

Low-dose helical computed tomography (CT) in the perioperative workup of adolescent idiopathic scoliosis.

The study aims were to estimate the radiation dose in patients examined with low dose spine CT and to compare it with that received by patients undergoing standard CT for trauma of the same region, as well as to evaluate the impact of dose reduction on image quality. Radiation doses in 113 consecutive low dose spine CTs were compared with those in 127 CTs for trauma. The inter- and intraobserver agreement in measurements of pedicular width, and vertebral rotation, measurements of signal-to-noise ratio and assessment of hardware status were the indicators in the evaluation of image quality. The effective dose of the low dose spine CT (0.37 mSv) was 20 times lower than that of a standard CT for trauma (13.09 mSv). This dose reduction conveyed no impact on image quality. This low dose spine CT protocol allows detailed evaluation that is necessary for preoperative planning and postoperative evaluation.

Surgical Outcomes of Anterior Versus Posterior Fusion in Lenke Type 1 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective study. OBJECTIVE: To describe surgical results in two and three dimensions and patient-reported outcomes of scoliosis treatment for Lenke type 1 idiopathic curves with an open anterior or posterior approach. SUMMARY OF BACKGROUND DATA: Different surgical techniques have been described to prevent curve progression and to restore spinal alignment in idiopathic scoliosis. The spine can be accessed via an anterior or a posterior approach. However, the surgical outcomes, especially in three dimensions, for different surgical approaches remain unclear. METHODS: Cohorts of Lenke curve type 1 idiopathic scoliosis patients, after anterior or posterior spinal fusion were recruited, to measure curve characteristics on conventional radiographs, before and after surgery and after 2 years follow-up, whereas the vertebral axial rotation, true mid-sagittal anterior-posterior height ratio of individual structures, and spinal height differences were measured on 3D reconstructions of the pre- and postoperative supine low-dose computed tomography (CT) scans. Additionally, the intraoperative parameters were described and the patients completed the Scoliosis Research Society outcomes and the 3-level version of EuroQol Group questionnaires postoperatively. RESULTS: Fifty-three patients with Lenke curve type 1 idiopathic scoliosis (26 in the anterior cohort and 27 in the posterior cohort) were analyzed. Fewer vertebrae were instrumented in the anterior cohort compared with the posterior cohort (P < 0.001), with less surgery time and lower intraoperative blood loss (P < 0.001). The Cobb angle correction of the primary thoracic curve directly after surgery was 57 ±â€Š12% in the anterior cohort and 73 ±â€Š12% in the posterior cohort (P < 0.001) and 55 ±â€Š13% and 66 ±â€Š12% (P = 0.001) at 2 years follow-up. Postoperative 3D alignment restoration and questionnaires showed no significant differences between the cohorts. CONCLUSION: This study suggests that Lenke type 1 curves can be effectively managed surgically with either an open anterior or posterior approach. Each approach, however, has specific advantages and challenges, as described in this study, which must be considered before treating each patient. LEVEL OF EVIDENCE: 3.

Nonoperatively treated burst fractures of the thoracic and lumbar spine in adults: a 23- to 41-year follow-up.

BACKGROUND CONTEXT: Several studies report a favorable short-term outcome after nonoperatively treated two-column thoracic or lumbar burst fractures in patients without neurological deficits. Few reports have described the long-term clinical and radiological outcome after these fractures, and none have, to our knowledge, specifically evaluated the long-term outcome of the discs adjacent to the fractured vertebra, often damaged at injury and possibly at an increased risk of height reduction and degeneration with subsequent chronic back pain. PURPOSE: To evaluate the long-term clinical and radiological outcome after nonoperatively treated thoracic or lumbar burst fractures in adults, with special attention to posttraumatic radiological disc height reduction. STUDY DESIGN: Case series. PATIENT SAMPLE: Sixteen men with a mean age of 31 years (range, 19-44) and 11 women with a mean age of 40 years (range, 23-61) had sustained a thoracic or lumbar burst fracture during the years 1965 to 1973. Four had sustained a burst fracture Denis type A, 18 a Denis type B, 1 a Denis type C, and 4 a Denis type E. Seven of these patients had neurological deficits at injury, all retrospectively classified as Frankel D. OUTCOME MEASURES: The clinical outcome was evaluated subjectively with Oswestry score and questions regarding work capacity and objectively with the Frankel scale. The radiological outcome was evaluated with measurements of local kyphosis over the fractured segment, ratios of anterior and posterior vertebral body heights, adjacent disc heights, pedicle widths, sagittal width of the spinal canal, and lateral and anteroposterior displacement. METHODS: From the radiographical archives of an emergency hospital, all patients with a nonoperatively treated thoracic or lumbar burst fracture during the years 1965 to 1973 were registered. The fracture type, localization, primary treatment, and outcome were evaluated from the old radiographs, referrals, and reports. Twenty-seven individuals were clinically and radiologically evaluated a mean of 27 years (range, 23-41) after the injury. RESULTS: At follow-up, 21 former patients reported no or minimal back pain or disability (Oswestry Score mean 4; range, 0-16), whereas 6 former patients (of whom 3 were classified as Frankel D at baseline) reported moderate or severe disability (Oswestry Score mean 39; range, 26-54). Six former patients were classified as Frankel D, and the rest as Frankel E. Local kyphosis had increased by a mean of 3 degrees (p<.05), whereas the discs adjacent to the fractured vertebrae remained unchanged in height during the follow-up. CONCLUSIONS: Nonoperatively treated burst fractures of the thoracic or lumbar spine in adults with or without minor neurological deficits have a predominantly favorable long-term outcome, and there seems to be no increased risk for subsequent disc height reduction in the adjacent discs.

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.

[Treatment of osteoporotic vertebral compression. Explosive interest for vertebroplasty and kyphoplasty]. / Behandling av osteoporotisk kotkompression. Explosionsartat intresse för vertebroplastik och kyfoplastik.

During the last 15 years, two new treatment strategies have gained worldwide attention in the treatment of osteoporotic vertebral fractures. The exponential increase in the use of percutaneous vertebro- or kyphoplasty has up to now not been supported by scientific sound evidence-based data. There exist no prospective randomised controlled trials (RCT) that support the efficacy of the treatments, not even adequate controlled studies. Instead we have to rely on prospective and retrospective uncontrolled short-term observational studies and case-control studies. These studies consistently indicate that the short-term results after the procedures in the treatment of osteoporotic vertebral fractures are favourable, regarding both pain relief and functional status. However, if a vertebro- or a kyphoplasty produces a better outcome than conservative treatment, and if the long-term results are as favourable as the short-term results in the treatment of osteoporotic vertebral fractures, is currently unknown.

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.