Convex-concave and anterior-posterior spinal length discrepancies in adolescent idiopathic scoliosis with major right thoracic curves versus matched controls.

PURPOSE: The apical deformation in adolescent idiopathic scoliosis (AIS) is a combination of rotation, coronal deviation and passive anterior lengthening of the spine. In AIS surgery, posterior-concave lengthening or anterior-convex shortening can be part of the corrective maneuver, as determined by the individual surgeon's technique. The magnitude of convex-concave and anterior-posterior length discrepancies, and how this needs to be modified to restore optimal spinal harmony, remains unknown. METHODS: CT-scans of 80 pre-operative AIS patients with right convex primary thoracic curves were sex- and age-matched to 80 healthy controls. The spinal length parameters of the main thoracic curves were compared to corresponding levels in controls. Vertebral body endplates and posterior elements were semi-automatically segmented to determine the length of the concave and convex side of the anterior column and along the posterior pedicle screw entry points while taking the 3D-orientation of each individual vertebra into account. RESULTS: The main thoracic curves showed anterior lengthening with a mean anterior-posterior length discrepancy of + 3 ± 6%, compared to a kyphosis of - 6 ± 3% in controls (p < 0.01). In AIS, the convex side was 20 ± 7% longer than concave (0 ± 1% in controls; p < 0.01). The anterior and posterior concavity were 7 and 22 mm shorter, respectively, while the anterior and posterior convexity were 21 and 8 mm longer compared to the controls. CONCLUSIONS: In thoracic AIS, the concave shortening is more excessive than the convex lengthening. To restore spinal harmony, the posterior concavity should be elongated while allowing for some shortening of the posterior convexity.

Osteocyte-specific dentin matrix protein 1 : the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing.

AIMS: There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. METHODS: A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. RESULTS: Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. CONCLUSION: The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465-476.

A Decade in Review after Idiopathic Scoliosis Was First Called a Complex Trait-A Tribute to the Late Dr. Yves Cotrel for His Support in Studies of Etiology of Scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.

Comparison of 3D and 2D characterization of spinal geometry from biplanar X-rays: a large cohort study.

BACKGROUND: Biplanar X-ray system providing anteroposterior and sagittal plane with an ultra-low radiation dose and in weight-bearing position is increasingly used for spine imaging. The original three-dimensional (3D) reconstruction method from biplanar X-rays has been widely used for clinical parameters, however, the main issue is that manual adjustments of the 3D model was quite time-consuming and limited to thoracolumbar spine. A quasi-automated 3D reconstruction method of the spine from cervical vertebra to pelvis was proposed, which proved fast and accurate in 57 patients with adolescent idiopathic scoliosis. The aim of this study was to compare the newly developed technique of quasi-automatic 3D measurement with classical 2D measurements in a large cohort. METHODS: A total of 494 adults with biplanar EOS X-ray scanning were included in this study and divided into health and deformity group according to the presence of spinal deformity. The proposed method of quasi-automatic 3D measurement was applied to all these subjects. The radiographic parameters included: thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sagittal vertical axis (SVA), T1 pelvic angle (TPA) in sagittal plane, and cobb angle in coronal plane. Comparison was made between quasi-automatic and manual measurement. RESULTS: The mean age was 53.7±19.9 years old. In the whole population, the mean differences between the two methods were 3.9° for TK (30.5°±9.9° vs. 26.5°±9.3°, P<0.001), -5.2° for LL (-47.5°±11.2° vs. -42.4°±11.0°, P<0.001), 3.6° for PI (46.9°±10.3° vs. 43.9°±10.3°, P<0.001), -0.2° for PT (11.9°±7.7° vs. 12.0°±8.2°, P=0.328), -2.1 mm for SVA (15.7±26.2 vs. 17.8±26.3 mm, P=0.221) and -1.1° for TPA (9.0°±7.6° vs. 10.1°±7.8°, P=0.051). The deformity group had similar mean differences with the asymptomatic group with the values ranged from -4.1° to 3.8° for sagittal parameters. The mean differences of Cobb angle were 1.9° for patients with Cobb angle <30° and 2.3° for patients with Cobb angle >30°, respectively. Correlation analysis showed r2 for all clinical parameters ranged from 0.667 to 0.923. On average, the new method takes 5 minutes to compute all the parameters for one case. CONCLUSIONS: In conclusion, this ergonomic and efficient quasi-automatic method for full spine proved fast and accurate measurement in a large population, which showed great potential in extensive clinical application.

Association of higher bone turnover with risk of curve progression in adolescent idiopathic scoliosis.

OBJECTIVE: Emerging evidence suggest abnormal bone metabolism and defective bone qualities are associated to etipathogenesis of Adolescent Idiopathic Scoliosis (AIS). Systemic low bone mass is important prognosticator to predict risk of curve progression in AIS. The underlying mechanism is still unclear. We hypothesize that aberrant bone turnover correlates with bone qualities in AIS and associates to risk of curve progression. SUBJECTS AND METHODS: Two cohorts were included in this study. The case-control study recruited 161 AIS girls and 161 ethnic/age-matched healthy girls. The longitudinal cohort recruited 128 AIS girls with two-year follow-up. Areal bone mineral density (BMD) at femoral necks were measured with dual-energy x-ray absorptiometry (DXA), and bone qualities of distal radius by high-resolution peripheral quantitative computed tomography (HR-pQCT). Time-lapse analysis of registered HR-pQCT images estimated local bone remodeling quantitatively. Serum levels of CTX and P1NP were measured with ELISA kits. RESULTS: AIS presented significantly higher serum level of P1NP. In both AIS and control, the negative correlations were consistently observed between serum CTX/P1NP levels and most cortical bone quality parameters after adjustment to age. Significant correlation between serum bone turnover markers and trabecular bone parameters have been observed only in control. Progressive AIS has significant increase of serum P1NP level at first clinic visit. Time lapse register analysis showed high bone resorption and low net bone gain was associated with risk of progression in AIS. CONCLUSIONS: Our study characterized AIS with higher serum bone turnover markers, which may contribute to defective bone qualities in AIS. For the first time, we showed that progressive AIS had higher systemic bone turnover markers level and local bone remodeling. This fresh evidence indicated association between disrupted bone turnover and risk of progression of AIS, which set the foundation of new prognostic method and of novel treatment target to curve progression. This study demonstrated the importance of bone metabolism in developing disease management of AIS to achieve goal of early prediction and non-surgical modulation.

An analysis of the interactions between the spine, pelvis, and lower limbs in asymptomatic adults with limited pelvic compensation.

BACKGROUND: The interactions between the spine, pelvis, and lower limbs are dynamic based on the "cone of economy" concept; thus, different global radiographic parameters could be regarded as reflections of different centers of gravity. We conducted this retrospective study to evaluate the offsets of different centers of gravity in asymptomatic populations and to investigate how the global sagittal alignment is supported. METHODS: The following parameters were measured: cervical lordosis, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), the ratio between PT and PI (PT/PI), sacral slope, PI minus LL (PI-LL), the sagittal vertical axis (SVA), cranial SVA to ankle center (Cr-A), CrSVA to the femoral head center (Cr-FH), C2SVA to the femoral head center (C2-FH), pelvic translation (P. Shift), and knee angle (KA). Participants were divided into subgroups based on the PT/PI ratio. Mean values were compared using the t-test, and correlations were assessed using Pearson's coefficient. RESULTS: A total of 82 asymptomatic adults were enrolled. The average PT/PI in subgroup 1 was the smallest, showing that individuals in this group may have limited pelvic retroversion. No significant differences in Cr-FH, Cr-A, or C2-FH were found between subgroups (all P>0.1), implying that global alignment was well supported in each group. Specifically, C2-FH showed minor changes between subgroups (P=0.998), showing that C2-FH may be a target for sagittal compensation. There were positive correlations between PT/PI and both P. Shift and SVA (r=0.930 and r=0.606, respectively). However, Cr-FH, Cr-A, and C2-FH were not significantly correlated with P. Shift or PT/PI (all P>0.05). Weak correlations existed between Cr-A, Cr-FH, and age (all P>0.2). CONCLUSIONS: This study revealed that the Cr-FH and C2-FH offsets are stable across the population and could be maintained by regulating only the sagittal spinal curvature when pelvic compensation is limited. Cr-FH is not affected by age in the asymptomatic population. Thus, the stable Cr-FH and C2-FH could provide references for surgeons during the surgical decision-making process in patients with adult spinal deformity with sagittal malalignment.

A computed tomography-based spatial reference for pedicle screw placement in adolescent idiopathic scoliosis.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine semiautomatically the 3D position of the pedicle axis in operative adolescent idiopathic scoliosis (AIS) patients relative to the operating table and the lamina, as orientation for pedicle screw placement for better understanding and reference of spine surgeons. Pedicle morphology is well described as the angle between the convex and concave pedicle. However, the pedicle angle as relative to the neutral anterior-posterior axis or to an easy-to-use intravertebral landmark, remained unknown. METHODS: The pedicles of the apex and two adjacent vertebrae cranial and caudal to the apex of 86 right-sided primary thoracic AIS curves were evaluated using semiautomatic 3D software on high-resolution CT scans, in the same prone position as during surgery. Pedicle vectors were obtained and calculated as transverse and sagittal angles, as relative to the neutral axis (corresponding with an axis perpendicular to the operating table) and to an axis perpendicular to the lamina. RESULTS: At the apex, the mean convex and concave transverse pedicle angles were 14.3º (95% confidence interval [95% CI]: 12.0-16.6) and 30.4º (95% CI: 28.1-32.8) to the right. The angles decreased toward the adjacent levels cranial and caudal to the apex (p < 0.001) and linearly increased with a higher Cobb angle (r ≥ 0.472; p < 0.001). The mean transverse pedicle-lamina angles, sagittal pedicle angles and the sagittal pedicle-lamina angles differed along the curve as well (p < 0.001). CONCLUSIONS: Pedicle angulation differs between convex and concave and depends on the position of the vertebra relative to the apex, as well as the curve severity. The transverse and sagittal pedicle angles, as relative to the operating table and laminae, could provide useful reference for better understanding of the distorted 3D morphology, and the angles, as given in this study, could serve as an approximate guideline for the expected direction of the pedicle screw. LEVEL OF EVIDENCE: Level IV.

A validated composite model to predict risk of curve progression in adolescent idiopathic scoliosis.

BACKGROUND: In adolescent idiopathic scoliosis (AIS), the continuous search for effective prognostication of significant curve progression at the initial clinical consultation to inform decision for timely treatment and to avoid unnecessary overtreatment remains a big challenge as evidence of the multifactorial etiopathogenic nature is increasingly reported. This study aimed to formulate a composite model composed of clinical parameters and circulating markers in the prediction of curve progression. METHOD: This is a two-phase study consisting of an exploration cohort (120 AIS, mean Cobb angle of 25°± 8.5 at their first clinical visit) and a validation cohort (51 AIS, mean Cobb angle of 23° ± 5.0° at the first visit). Patients with AIS were followed-up for a minimum of six years to formulate a composite model for prediction. At the first visit, clinical parameters were collected from routine clinical practice, and circulating markers were assayed from blood. FINDING: We constructed the composite predictive model for curve progression to severe Cobb angle > 40° with a high HR of 27.9 (95% CI of 6.55 to 119.16). The area under curve of the composite model is higher than that of individual parameters used in current clinical practice. The model was validated by an independent cohort and achieved a sensitivity of 72.7% and a specificity of 90%. INTERPRETATION: This is the first study proposing and validating a prognostic composite model consisting of clinical and circulating parameters which could quantitatively evaluate the probability of curve progression to a severe curvature in AIS at the initial consultation. Further validation in clinic will facilitate application of composite model in assisting objective clinical decision.

Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1-4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non-AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid-etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone-like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC-Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy-dispersive X-ray spectroscopy analysis demonstrated a lower calcium-to-phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno-canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS.-Chen, H., Zhang, J., Wang, Y., Cheuk, K.-Y., Hung, A. L. H., Lam, T.-P., Qiu, Y., Feng, J. Q., Lee, W. Y. W., Cheng, J. C. Y. Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

CT-based study of vertebral and intravertebral rotation in right thoracic adolescent idiopathic scoliosis.

PURPOSE: To define the longitudinal rotation axis around which individual vertebrae rotate, and to establish the various extra- and intravertebral rotation patterns in thoracic adolescent idiopathic scoliosis (AIS) patients, for better understanding of the 3D development of the rotational deformity. METHODS: Seventy high-resolution CT scans from an existing database of thoracic AIS patients (Cobb angle: 46°-109°) were included to determine the vertebral axial rotation, rotation radius, intravertebral axial rotation, and local mechanical torsion for each spinal level, using previously validated image processing techniques. RESULTS: For all levels, the longitudinal rotation axis, from which the vertebrae rotate away from the midline, was localized posterior to the spine. The axis became closer to the spine at the apex: apex, r = 11.5 ± 5.1 cm versus two levels above (radius = 15.8 ± 8.5 cm; p < 0.001) and beneath (radius = 14.2 ± 8.2 cm; p < 0.001). The vertebral axial rotation, intravertebral axial rotation, and local mechanical torsion of the vertebral bodies were largest at the apex (21.9° ± 7.4°, 8.7° ± 13.5° and 3.0° ± 2.5°) and decreased toward the neutral, junctional zones (p < 0.001). CONCLUSION: In AIS, the vertebrae rotate away around an axis that is localized posterior to the spine. The distance between this axis and the spine is minimal at the apex and increases gradually to the neutral zones. The vertebral axial rotation is accompanied by smaller amounts of intravertebral rotation and local mechanical torsion, which increases toward the apical region. The altered morphology and alignment are important for a better understanding of the 3D pathoanatomical development of AIS and better therapeutic planning for bracing and surgical intervention. These slides can be retrieved under Electronic Supplementary Material.

Bone measurements at multiple skeletal sites in adolescent idiopathic scoliosis-an in vivo correlation study using DXA, HR-pQCT and QCT.

Significant correlations for bone mineral density and bone microstructure between spinal and non-spinal skeletal sites (distal radius and proximal femur) in adolescent idiopathic scoliosis (AIS) patients were observed, indicating that proximal femoral DXA and distal radial HR-pQCT could provide valid clinical assessments in patients with AIS. PURPOSE: Low bone mass is an important feature of adolescent idiopathic scoliosis (AIS), which is a complex 3D spinal deformity that affects girls during puberty. However, no clinical imaging modality is suitable for regular monitoring on their spinal bone qualities in rapid growth period. Therefore, we investigated whether bone mineral density (BMD) and bone microstructure at non-spinal sites correlated with BMD and mechanical property in the spine in AIS patients. METHODS: Thirty-two AIS girls (16.7 ± 3.5 years old with mean Cobb angle of 67 ± 11°) who underwent pre-operative spine CT examination for navigation surgery were recruited. Volumetric BMD (vBMD) of lumbar spine (LS) was measured by quantitative computed tomography (QCT), vBMD and bone microstructure of distal radius (DR) by high-resolution peripheral QCT (HR-pQCT) and areal BMDs of total hip (TH) and femoral necks (FN) by dual-energy X-ray absorptiometry (DXA). Biomechanical properties of the DR and LS were estimated by finite element analysis (FEA). Pearson correlation was performed to study the correlation between bone parameters at these three sites. RESULTS: LS vBMD correlated significantly with both FN and TH aBMD (R = 0.663-0.725, both p < 0.01) and with DR microstructural parameters (R = 0.380-0.576, all p < 0.05). Mechanical properties of LS and DR were also correlated (R = 0.398, p = 0.039). CONCLUSIONS: Bone measurement at proximal femur and distal radius could provide an additional predictive power in estimating the bone changes at spine, which is the primary site of deformity in AIS patients. Our result indicated that DXA and HR-pQCT could provide a valid surrogate for spine bone measurements in AIS patients.

A Genetic Predictive Model Estimating the Risk of Developing Adolescent Idiopathic Scoliosis.

BACKGROUND: Previous GWASs have revealed several susceptible variants associated with adolescent idiopathic scoliosis (AIS). Risk prediction based on these variants can potentially improve disease prognosis. We aimed to evaluate the combined effects of genetic factors on the development of AIS and to further develop a genetic predictive model. METHODS: A total of 914 AIS patients and 1441 normal controls were included in the discovery stage, which was followed by the replication stage composed of 871 patients and 1239 controls. Genotyping assay was performed to analyze 10 previously reported susceptible variants, including rs678741 of LBX1, rs241215 of AJAP1, rs13398147 of PAX3, rs16934784 of BNC2, rs2050157 of GPR126, rs2180439 of PAX1, rs4940576 of BCL2, rs7593846 of MEIS1, rs7633294 of MAGI1 and rs9810566 of TNIK. Logistic regression analysis was performed to generate a risk predictive model. The predicted risk score was calculated for each participant in the replication stage. RESULTS: The association of the 10 variants with AIS was successfully validated. The established model could explain approximately 7.9% of the overall variance. In the replication stage, patients were found to have a remarkably higher risk score as compared to the controls (44.2 ± 14.4 vs. 33.9 ± 12.5, p <0.001). There was a remarkably higher proportion of the risk score i.e. >40 in the patients than in the controls (59% vs. 28.9%, p <0.001). CONCLUSION: Risk predictive model based on the previously reported genetic variants has a remarkable discriminative power. More clinical and genetic factors need to be studied, to further improve the proba-bility to predict the onset of AIS.

Global sagittal alignment in elderly patients with osteoporosis and its relationship with severity of vertebral fracture and quality of life.

We compared global sagittal alignment and quality of life in osteoporotic patients with and without vertebral compression fracture (VCF) and determined its relationship with VCF severity. The findings revealed osteoporotic patients with VCF showed decreased quality of life and worse global sagittal alignment, which was significantly associated with VCF severity. INTRODUCTION: The aim of this study was to compare the global sagittal alignment and quality of life in elderly osteoporotic patients with and without vertebral compression fracture (VCF), and to investigate the relationship between global sagittal alignment and severity of VCF. METHODS: A consecutive series of 72 female patients with osteoporosis aged over 60 years and 31 age-matched females without osteoporosis were prospectively enrolled. The patients were divided into VCF and non-VCF group. Patient's clinical demography, nature of VCF, and bone mineral density (BMD) were also recorded. Spinal deformity index was used to evaluate severity of VCF. EOS® biplanar imaging system was then used to evaluate global sagittal parameters: T1 pelvic angle (TPA) and global sagittal angle (GSA). In addition, quality of life was assessed with self-reported questionnaires: the Oswestry Disability Index (ODI) and Short-form 12 (SF-12). RESULTS: Osteoporotic patients and controls were found to be significantly different in terms of TPA, GSA, and BMD. And in patients with VCF, they were found to have significantly higher TPA and GSA. TPA and GSA were significantly correlated with SF-12 and ODI. The number of VCF and SDI significantly correlated with global sagittal alignment. Using regression analysis, parameters significantly associated with abnormal global alignment were the number of VCF (OR = 1.13) and SDI (OR = 1.84). CONCLUSION: Osteoporotic patients with VCF showed worse global sagittal alignment and decreased quality of life. The number and severity of VCF had a negative influence on global sagittal balance, which indicates that poorer sagittal global alignment may imply worse quality of life and more severe VCF.

Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and ß-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active ß-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Anterior-posterior length discrepancy of the spinal column in adolescent idiopathic scoliosis-a 3D CT study.

BACKGROUND CONTEXT: One of the characteristics of reported observations in adolescent idiopathic scoliosis (AIS) is that the thoracic spine is longer anteriorly than posteriorly, more pronounced around the apex than the transitional zones. This reversal of the normal kyphotic anatomy of the thoracic spine is related to questions of etiopathogenesis of AIS. The changes in the anatomy of the anterior column have been described rather in detail; however, the role of the posterior spinal column and the laminae has so far not been elucidated. If the posterior column exhibits a longitudinal growth disturbance, it could act as a tether, leading to a more or less normal anterior column with a deformed and shorter posterior aspect of the spine. So far, it has remained unclear whether this anterior-posterior length discrepancy is the result of relative anterior lengthening or relative posterior shortening, and which tissues (bone, disc, intervertebral soft tissue) are involved. PURPOSE: The present study aimed to compare the discrepancy of the anterior-posterior length of the spinal column in the "true" midsagittal plane of each vertebra in patients with idiopathic scoliosis versus controls, using three-dimensional computed tomography (CT) scans. STUDY DESIGN/SETTING: This is a cross-sectional study. PATIENT SAMPLE: The sample consisted of computed tomography scans of 80 patients with moderate to severe AIS (Cobb angle: 46°-109°) before scoliosis navigation surgery and 30 non-scoliotic age-matched controls. OUTCOME MEASURES: The height of the osseous and non-osseous structures from anterior to posterior in the "true" midsagittal plane has been determined: the anterior side of the vertebral body and disc, the posterior side of the vertebral body and disc, the lamina and interlaminar space and the spinous process and interspinous space, as well as the height ratios between the anterior column and posterior structures of the primary thoracic and lumbar AIS curves and corresponding levels in non-scoliotic controls. METHODS: Semiautomatic software was used to reconstruct and measure the parameters in the true midsagittal plane of each vertebra and intervertebral structure that are rotated and tilted in a different way. RESULTS: In AIS, the anterior height of the thoracic curve was 3.6±2.8% longer than the posterior height, 2.0±6.1% longer than the length along the laminae, and 8.7±7.1% longer than the length along the spinous processes, and this differed significantly from controls (-2.7±2.4%, -7.4±5.2%, and +0.7±7.8%; p<.001). The absolute height of the osseous parts did not differ significantly between AIS and controls in the midsagittal plane. In contrast, the intervertebral structures contributed significantly to the observed length discrepancies. In absolute lengths, the anterior side of the disc of the thoracic curve was higher in AIS (5.4±0.8 mm) than controls (4.8±1.0 mm; p<.001), whereas the interspinous space was smaller in AIS (12.3±1.4 mm vs. 14.0±1.6 mm; p<.001). CONCLUSIONS: Based on this in vivo analysis, the true three-dimensional anterior-posterior length discrepancy of AIS curves was found to occur through both anterior column lengthening and posterior column shortening, with the facet joints functioning as the fulcrum. The vertebrae contribute partly to the anterior-posterior length discrepancy accompanied by more significant and possibly secondary increased anterior intervertebral discs height.

Association between braced curve behavior by pubertal growth peak and bracing effectiveness in female idiopathic scoliosis: a longitudinal cohort study.

BACKGROUND: Pre-pubertal idiopathic scoliosis (IS) is associated with high risk of bracing ineffectiveness. Integrated multidimensional maturity assessments are useful but complex to predict the high-risk occurrence of curve progression. This study is designed to provide a simple screening method for brace effectiveness by determining whether or not the braced curve behavior at growth spurt, being defined as variations in Cobb angle velocity (AV) at peak height velocity (PHV), can be a new factor predictive of brace outcome prescribed before PHV. METHODS: This is a retrospective study of a series of 35 IS girls with simplified skeletal maturity score no more than 3 at initiation of bracing treatment and followed up through the growth spurt until brace weaning or surgery. Serial Cobb angle and maturity indicators involving height velocity, Risser sign, triradiate cartilage, simplified skeletal maturity score and distal radius and ulna classification were assessed and patients were stratified into either a positive or negative category based on a positive or negative value of AV at PHV. Comparisons were made between the positive and negative AV groups, as well as the failed and successful bracing groups, using independent sample T test and crosstab analysis. Logistic regression analysis was used to identify the predictive factors of failed brace treatment. RESULTS: Brace treatment prescribed before PHV was found to have an overall failure rate of 57.1% and a surgical rate of 45.7%. Negative AV at PHV accounting for 54.3% of the recruited patients were associated with lower brace failure rate (36.8% vs. 81.2%, p = 0.016) and surgical rate (21.1% vs. 75.0%, p = 0.002). Patients in the failed bracing group showed higher ratio of thoracic curve (80.0% vs. 26.7%,p = 0.002) and higher AV at growth peak (2.3 ± 9.1 vs. -6.5 ± 11.4°/yrs., p = 0.016). The logistic regression analysis revealed that positive AV at PHV (OR = 9.268, 95% CI = 1.279-67.137, p = 0.028) and thoracic curve type (OR = 13.391, 95% CI = 2.006-89.412, p = 0.007) were strong predictive factors of ineffective brace treatment initiated before PHV. CONCLUSIONS: Sustained curve correction following bracing despite early onset and rapid pubertal growth was strongly predictive of effective brace control of scoliosis.

What Is the Actual 3D Representation of the Rib Vertebra Angle Difference (Mehta Angle)?

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the relevance of the conventional two-dimensional (2D) rib vertebra angle difference (RVAD) and the relationship with the complex three-dimensional (3D) apical morphology in scoliosis. SUMMARY OF BACKGROUND DATA: The RVAD, also known as Mehta angle, describes apical rib asymmetry on conventional radiographs and was introduced as a prognostic factor for curve severity in early onset scoliosis, and later applied to other types of scoliosis as well. METHODS: An existing idiopathic scoliosis database of high-resolution computed tomography scans used in previous work, acquired for spinal navigation, was used. Eighty-eight patients (Cobb angle 46°-109°) were included. Cobb angle and 2D RVAD, as described by Mehta, were measured on the conventional radiographs and coronal digitally reconstructed radiographs (DRR) of the prone computed tomography scans. A previously validated, semiautomatic image processing technique was used to acquire complete 3D spinal reconstructions for the measurement of the 3D RVAD in a reconstructed true coronal plane, axial rotation, and sagittal morphology. RESULTS: The 2D RVAD on the x-ray was on average 25.3°â€Š±â€Š11.0° and 25.6°â€Š±â€Š12.8° on the DRR (P = 0.990), but in the true 3D coronal view of the apex, hardly any asymmetry remained (3D RVAD: 3.1°â€Š±â€Š12.5°; 2D RVAD on x-ray and DRR vs. 3D RVAD: P < 0.001). 2D apical rib asymmetry in the anatomical coronal plane did not correlate with the same RVAD measurements in the 3D reconstructed coronal plane of the rotated apex (r = 0.155; P = 0.149). A larger 2D RVAD was found to correlate linearly with increased axial rotation (r = 0.542; P < 0.001) and apical lordosis (r = 0.522; P < 0.001). CONCLUSION: The 2D RVAD represents a projection-based composite radiographic index reflecting the severity of the complex 3D apical morphology including axial rotation and apical lordosis. It indicates a difference in severity of the apical deformation. LEVEL OF EVIDENCE: 4.

Thumb Ossification Composite Index (TOCI) for Predicting Peripubertal Skeletal Maturity and Peak Height Velocity in Idiopathic Scoliosis: A Validation Study of Premenarchal Girls with Adolescent Idiopathic Scoliosis Followed Longitudinally Until Skeletal Maturity.

BACKGROUND: Accurate skeletal maturity assessment is important to guide clinical evaluation of idiopathic scoliosis, but commonly used methods are inadequate or too complex for rapid clinical use. The objective of the study was to propose a new simplified staging method, called the thumb ossification composite index (TOCI), based on the ossification pattern of the 2 thumb epiphyses and the adductor sesamoid bone; to determine its accuracy in predicting skeletal maturation when compared with the Sanders simplified skeletal maturity system (SSMS); and to validate its interrater and intrarater reliability. METHODS: Hand radiographs of 125 girls, acquired when they were newly diagnosed with idiopathic scoliosis prior to menarche and during longitudinal follow-up until skeletal maturity (a minimum of 4 years), were scored with the TOCI and SSMS. These scores were compared with digital skeletal age (DSA) and radius, ulna, and small hand bones (RUS) scores; anthropometric data; peak height velocity; and growth-remaining profiles. Correlations were analyzed with the chi-square test, Spearman and Cramer V correlation methods, and receiver operating characteristic curve analysis. Reliability analysis using the intraclass correlation (ICC) was conducted. RESULTS: Six hundred and forty-five hand radiographs (average, 5 of each girl) were scored. The TOCI staging system was highly correlated with the DSA and RUS scores (r = 0.93 and 0.92, p < 0.01). The mean peak height velocity (and standard deviation) was 7.43 ± 1.45 cm/yr and occurred at a mean age of 11.9 ± 0.86 years, with 70.1% and 51.4% of the subjects attaining their peak height velocity at TOCI stage 5 and SSMS stage 3, respectively. The 2 systems predicted peak height velocity with comparable accuracy, with a strong Cramer V association (0.526 and 0.466, respectively; p < 0.01) and similar sensitivity and specificity on receiver operating characteristic curve analysis. The mean age at menarche was 12.57 ± 1.12 years, with menarche occurring over several stages in both the TOCI and the SSMS. The growth remaining predicted by TOCI stage 8 matched well with that predicted by SSMS stage 7, with a mean of <2 cm/yr of growth potential over a mean of <1.7 years at these stages. The TOCI also demonstrated excellent reliability, with an overall ICC of >0.97. CONCLUSIONS: The new proposed TOCI could provide a simplified staging system for the assessment of skeletal maturity of subjects with idiopathic scoliosis. The index needs to be subjected to further multicenter validation in different ethnic groups.

The Height-Width-Depth Ratios of the Intervertebral Discs and Vertebral Bodies in Adolescent Idiopathic Scoliosis vs Controls in a Chinese Population.

Adolescent idiopathic scoliosis (AIS) patients have been reported to be taller and more slender than normal controls, suggesting less mechanical stiffness of their trunk and spine. For assessment of mechanical stiffness, to our best knowledge this is the first to study height-width-depth relations at the level of the individual vertebra and disc in 3-D and to evaluate its relation with the Cobb angle severity. A unique series of high-resolution pre-operative computed tomographic (CT) scans of a total of 105 Chinese patients with moderate to severe AIS and 11 age-matched non-scoliotic controls were used for this study. It was found that some geometric relations differed between primary thoracic curves, secondary curves and normal controls at the individual affected vertebra and disc level. The scoliotic discs in the primary curves were relatively more slender (taller and thinner) than in secondary curves and as compared to controls. In the lumbar spinal area, the vertebral bodies were more slender in the primary as well as secondary AIS curves as compared to the controls. Therefore, if all material properties remain the same, our finding indicates that scoliotic spines may be mechanically less stiff than normal spines. No significant correlation between any of the measures and Cobb angle severity was found.