3D Deformation Patterns of S Shaped Elastic Rods as a Pathogenesis Model for Spinal Deformity in Adolescent Idiopathic Scoliosis.
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SUBMITTER: Pasha S
PROVIDER: S-EPMC6848095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS.
| S-EPMC5214167 | biostudies-literature
Project description:The cellular and molecular mechanisms underlying spinal deformity progression in adolescent idiopathic scoliosis (AIS) remain poorly understood. In this study, 804 French-Canadian patients and 278 age- and sex-matched controls were enrolled and genotyped for 12 single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene or its promoter. The plasma YKL-40 levels were determined by ELISA. We showed that elevation of circulating YKL-40 levels was correlated with a reduction of spinal deformity progression risk. We further identified significant associations of multiple CHI3L1 SNPs and their haplotypes with plasma YKL-40 levels and scoliosis severity as a function of their classification in a specific endophenotype. In the endophenotype FG3 group, we found that patients harboring the haplotype G-G-A-G-G-A (rs880633|rs1538372|rs4950881|rs10399805|rs6691378|rs946261), which presented in 48% of the cases, showed a positive correlation with the plasma YKL-40 levels (P = 7.6 × 10-6 and coefficient = 36). Conversely, the haplotype A-A-G-G-G-G, which presented in 15% of the analyzed subjects, showed a strong negative association with the plasma YKL-40 levels (P = 2 × 10-9 and coefficient = -9.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (P = 9.9 × 10-6 and coefficient = -13.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (P = 1.6 × 10-7 and coefficient = -10.08) than males (P = 0.0021 and coefficient = -9.01). At the functional level, we showed that YKL-40 treatments rescued Gi-coupled receptor signalling dysfunction occurring in primary AIS osteoblasts. Collectively, our findings reveal a novel role for YKL-40 in AIS pathogenesis and a new molecular mechanism interfering with spinal deformity progression.
| S-EPMC6450973 | biostudies-literature
Project description:Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear. To gain an insight into AIS pathogenesis, this review searched PubMed database up to June 2019, using key words or medical subject headings terms including "adolescent idiopathic scoliosis," "scoliosis," "pathogenesis," "etiology," "genetics," "mesenchymal stem cells," and their combinations, summarized existing literatures and categorized the theories or hypothesis into nine aspects. These aspects include bone marrow mesenchymal stem cell studies, genetic studies, tissue analysis, spine biomechanics measurements, neurologic analysis, hormone studies, biochemical analysis, environmental factor analysis, and lifestyle explorations. These categories could be a guidance for further etiology or treatment researches to gain inspiration.
| S-EPMC7046244 | biostudies-literature
Project description:AimTo evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.MethodsSelection criteria(1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other.Search methodOvid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.ResultsThe review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.ConclusionThis review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.
| S-EPMC4539477 | biostudies-literature
Project description:PurposeThis article examines if longer posterior spinal fusions with instrumentation (PSFI) into the lumbar spine (L3/4) alter spinopelvic parameters compared with selective fusions to T12/L1/L2 in adolescent idiopathic scoliosis (AIS) patients.MethodsWe analysed radiographs of 84 AIS patients, 58 (69%) females and 26 (31%) males, who underwent PSFI at an mean age of 15 years ± 2.5 years, range 10 years to 21 years, between 1st January 2007 and 31st December 2014. Radiographic parameters were measured pre- and post-operatively at most recent follow-up (range 2 years to 8.2 years): pelvic incidence (PI), lumbar lordosis (LL, L1-S1 and L4-S1), sagittal vertical alignment (SVA), scoliosis angle and proximal junctional kyphosis (PJK). PI-LL was calculated. Data was analysed using t-tests or Wilcoxon rank-sum tests.ResultsIn total, 32 patients underwent a selective fusion with lowest instrumented vertebra (LIV) T12-L2, and 52 patients underwent a fusion with LIV L3-L4. In both groups, scoliosis angle was significantly corrected at follow-up (p < 0.005).Pre-operatively, both groups had similar LL (L1-S1) and PI-LL. Post-operatively, LL increased in the L3-4 fusion group (p < 0.005) but did not change in the selective fusion group (p = 0.116). This change in LL in the L3-4 fusion group affected the post-operative PI-LL (T12-L2 fusion -4.9° versus L3-4 fusion -13.6°, p = 0.002). No differences were seen in PI, SVA or LL L4-S1 between groups. Radiographic PJK occurred in seven of the L3-4 patients with and without PJK (noPJK -8.8° versus PJK -25.8°, p = 0.026).ConclusionsIn patients who underwent a fusion ending at L3 or L4, LL was increased. This altered the PI-LL relationship, and appeared to increase the risk of PJK.Level of evidenceIII.
| S-EPMC7740676 | biostudies-literature
Project description:Several theories have been proposed to explain the etiology of adolescent idiopathic scoliosis (AIS) until present. However, limited data are available regarding the impact of vitamin D insufficiency or deficiency on scoliosis. Previous studies have shown that vitamin D deficiency and insufficiency are prevalent in adolescents, including AIS patients. A series of studies conducted in Hong Kong have shown that as many as 30% of these patients have osteopenia. The 25-hydroxyvitamin D3 level has been found to positively correlate with bone mineral density (BMD) in healthy adolescents and negatively with Cobb angle in AIS patients; therefore, vitamin D deficiency is believed to play a role in AIS pathogenesis. This study attempts to review the relevant literature on AIS etiology to examine the association of vitamin D and various current theories. Our review suggested that vitamin D deficiency is associated with several current etiological theories of AIS. We postulate that vitamin D deficiency and/or insufficiency affects AIS development by its effect on the regulation of fibrosis, postural control, and BMD. Subclinical deficiency of vitamin K2, a fat-soluble vitamin, is also prevalent in adolescents; therefore, it is possible that the high prevalence of vitamin D deficiency is related to decreased fat intake. Further studies are required to elucidate the possible role of vitamin D in the pathogenesis and clinical management of AIS.
| S-EPMC6284127 | biostudies-other
Project description:BackgroundA misbalance in forces is proposed for causing adolescent idiopathic scoliosis (AIS). AIS is therefore correlated to adjacent musculoskeletal pathologies. Its concomitance with idiopathic pectus deformities (PD) is underexposed. This systematic review analyzes the clinical significance and predictive factors of PD-associated AIS.MethodsA search was performed in PubMed, UpToDate, Embase, and Cochrane. A study was included if it: assessed the association between PD and scoliosis (category I), reported a prevalence of scoliosis in PD patients (category II), or addressed other topics about PD-associated AIS (category III). Studies in category I discussing predictive factors were appraised using the Quality in Prognosis Studies tool. Because of heterogeneity among the studies, predictive factors were analyzed according to a best evidence synthesis. A mean prevalence of scoliosis in PD patients was calculated using category I and II. Category III was narratively reviewed.ResultsForty-eight studies were included (I:19, II:21, III:8). Category I comprised 512 patients with PD-concomitant scoliosis. Thirteen studies reported predictive factors, of which 15 concerned the prevalence of scoliosis in PD patients and 12 Cobb Angle (CA) change after PD correction. Compared with AIS, PD seems to develop earlier in adolescence, and PD with concomitant AIS was more frequently reported in older patients. Evidence remained conflicting regarding the association between the severity of PD and that of scoliosis. As opposed to at a younger age, late PD correction is not associated with a postoperative increase of CA. Limited evidence showed that patients with a high CA undergoing PD correction do not experience an increase in CA, though, strong evidence indicated that it would not lead to a decrease in CA. The mean probable prevalence of AIS in PD patients was 13.1%.ConclusionCurrent literature confirms the association between PD and AIS in patients with an indication for PD correction.Level of evidence: III.
| S-EPMC9256832 | biostudies-literature
Project description:Adolescent idiopathic scoliosis (AIS) is associated with decreased respiratory quality of life and impaired diaphragm function. Recent hyperpolarized helium (HHe) MRI studies show alveolarization continues throughout adolescence, and mechanical forces are known to impact alveolarization. We therefore hypothesized that patients with AIS would have alterations in alveolar size, alveolar number, or alveolar septal dimensions compared to adolescents without AIS, and that posterior spinal fusion (PSF) might reverse these differences. We conducted a prospective observational trial using HHe MRI to test for changes in alveolar microstructure in control and AIS subjects at baseline and one year. After obtaining written informed consent from subjects' legal guardians and assent from the subjects, we performed HHe and proton MRI in 14 AIS and 16 control subjects aged 8-21 years. The mean age of control subjects (12.9 years) was significantly less than AIS (14.9 years, p = 0.003). At baseline, there were no significant differences in alveolar size, number, or alveolar duct morphometry between AIS and control subjects or between the concave (compressed) and convex (expanded) lungs of AIS subjects. At one year after PSF AIS subjects had an increase in alveolar density in the formerly convex lung (p = 0.05), likely reflecting a change in thoracic anatomy, but there were no other significant changes in lung microstructure. Modeling of alveolar size over time demonstrated similar rates of alveolar growth in control and AIS subjects in both right and left lungs pre- and post-PSF. Although this study suffered from poor age-matching, we found no evidence that AIS or PSF impacts lung microstructure. Trial registration: Clinical trial registration number NCT03539770.
| S-EPMC7544066 | biostudies-literature
Project description:BackgroundScoliotic braces are the standard of curve for management of moderate spinal deformities in pediatric patients. The effectiveness of this treatment method has been shown; however, the spinal and rib cage parameters, in the three anatomical planes, that are associated with bracing outcome in adolescent idiopathic scoliosis (AIS) are not fully identified.MethodsA total number of 45 right thoracic AIS patients who had received a thoraco-lumbo-scaral brace for the first time were included retrospectively. For each patient, radiographic images at three visits, pre-brace, in-brace, and at least 1 year after the first brace fit were included. Age, sex, Risser sign, and curve type at pre-brace, and thoracic and lumbar frontal and sagittal Cobb angles, thoracic and lumbar apical rotations, sagittal and frontal balances at pre-brace and in-brace were determined. Two sagittal curve types (hypothoracolumbar and normal/hyperthoracolumbar kyphosis), two rib cage types based on the costovertebral joints (drooping and horizontal), and two axial shapes of the spine (S shaped and V shaped) were used to stratify the patients. Feature selection and linear regression with regularization determined the parameters and the interaction terms that predicted the brace effectiveness significantly.ResultsSmaller in-brace thoracic Cobb and larger in-brace lordosis predicted brace effectiveness, p < 0.05. Impact of the out of brace lordosis on the brace success increased as the in brace kyphosis angle decreased, p = 0.046. A larger out of brace lordosis in hypothoracolumbar sagittal profile type patients improved the outcomes, p = 0.031. A smaller out of brace thoracic rotation improved the bracing outcomes in patients with horizontal ribs, p = 0.040.ConclusionBoth 3D patient specific parameters (lordosis, thoracic rotation, shape of the rib cage, and sagittal profile) and brace design (which allows larger in brace lordosis, better in brace Cobb correction) are important predictors of the brace effectiveness in AIS.
| S-EPMC6706918 | biostudies-literature
Project description:Adolescents with idiopathic scoliosis (AIS) often receive conservative treatments aiming to prevent progression of the spinal deformity during puberty. This study aimed to explore patient adherence and secondary outcomes during the first 6 months in an ongoing randomised controlled trial of three treatment interventions. Interventions consisted of physical activity combined with either hypercorrective Boston brace night shift (NB), scoliosis-specific exercise (SSE), or physical activity alone (PA). Measures at baseline and 6 months included angle of trunk rotation (ATR), Cobb angle, International Physical Activity Questionnaire short form (IPAQ-SF), pictorial Spinal Appearance Questionnaire (pSAQ), Scoliosis Research Society (SRS-22r), EuroQol 5-Dimensions Youth (EQ-5D-Y) and Visual Analogue Scale (EQ-VAS). Patient adherence, motivation, and capability in performing the intervention were reported at 6 months. The study included 135 patients (111 females) with AIS and >1-year estimated remaining growth, mean age 12.7 (1.4) years, and mean Cobb angle 31 (±5.3). At 6 months, the proportion of patients in the groups reporting high to very high adherence ranged between 72 and 95%, while motivation ranged between 65 and 92%, with the highest proportion seen in the NB group (p = 0.014, p= 0.002). IPAQ-SF displayed significant between group main effects regarding moderate activity (F = 5.7; p = 0.004; ηp2 = 0.10), with a medium-sized increase favouring the SSE group compared to NB. Walking showed significant between group main effects, as did metabolic equivalent (MET-min/week), with medium (F = 6.8, p = 0.002; ηp2 = 0.11, and large (F = 8.3, p = < 0.001, ηp2 = 0.14) increases, respectively, for the SSE and PA groups compared to NB. From baseline to 6 months, ATR showed significant between group medium-sized main effects (F = 1.2, p = 0.019, ηp2 = 0.007) favouring the NB group compared to PA, but not reaching a clinically relevant level. In conclusion, patients reported high adherence and motivation to treatment, especially in the NB group. Patients in the SSE and PA groups increased their physical activity levels without other clinically relevant differences between groups in other clinical measures or patient-reported outcomes. The results suggest that the prescribed treatments are viable first-step options during the first 6 months.
| S-EPMC8585057 | biostudies-literature