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Xiang Li,1,2 Guangsheng Li,1,3 Keith Dip-Kei Luk,1 Yong Hu1–3 1Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, 2Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 3Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China Background: Cervical spondylotic myelopathy (CSM) is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model. Materials and methods: A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1); CSM model with 4-week chronic compression (group 2), 2 weeks (group 3) and 4 weeks (group 4) after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI) test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs). Neuropathological change was evaluated by histological examinations. Results: MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52), ladder rung walking test (p < 0.05, F = 14.21) and latencies (p < 0.05, F = 5.76) and amplitudes (p < 0.05, F = 3.8) of SEP. Neuronal degeneration was obvious in the ventral horn with gradual restoration. After decompression, the motor neuron number in the ventral horn did not show significant changes (p > 0.05). However, increasing trend of myelin area and staining intensity were observed in all columns of the white matter (p < 0.05) after decompression, especially in the compressed lateral column. Conclusion: The established rat model is able to simulate histopathological characteristics of cervical myelopathy in human beings. The neuropathological change demonstrated that neurorestoratology in the myelopathic spinal cord would probably attribute to axonal remyelination of the white matter, but there would be an incapability of neuronal regeneration. Keywords: neurorestoratology, surgical decompression, chronic spinal cord injury, animal model, cervical spondylotic myelopathy

Study Design: Lateral radiographs of the lumbar spine were taken of 40 patients with lumbar spondylolisthesis. These radiographs were taken in the neutral, flexion, and extension positions for both erect and recumbent postures, and also in the prone and supine positions with traction applied via a traction table.Objectives: To define and demonstrate the presence of "vertical instability" in spondylolisthesis, and to determine the most useful radiographic views for clinical purposes and analysis of the surgical principle.Summary Of Background Data: Lateral radiographs of patients in flexion and extension are widely used to obtain quantitative and qualitative data on lumbar spondylolisthesis. Changes in lumbar disc height and segmental translation in a group of patients with spondylolisthesis have been demonstrated with the addition of traction and compression.Methods: Lateral and flexion extension radiographs of the lumbosacral spine in 37 patients with spondylolisthesis taken in standing and recumbent positions and under pelvic traction in the prone or supine positions were suitable for analysis. The changes in disc area, intervertebral kyphotic slip angle, and amount of anteroposterior shift (olisthesis) were measured from the radiographs using a computer digitizer. The disc area was normalized against the area of the superior vertebra, and the amount of anteroposterior shift was normalized against the anteroposterior width of the superior vertebra. Inter- and intraobserver error was found to be negligible, and results were analyzed by paired t test.Results: Maximum slip angle, maximum olisthesis, and minimum normalized disc area were found with the subject under erect flexion. Conversely, prone traction and recumbent extension produced minimum slip angle, whereas the lowest anteroposterior shifts were seen with the subject under prone and supine traction. Prone traction also resulted in a significantly larger normalized disc area than any other posture. The change in kyphotic slip angle between erect flexion and prone traction is correlated with the change in normalized olisthesis and disc area.Conclusions: Erect flexion and prone traction radiographs represent the extremes of subluxation and reduction of the olisthesis, respectively, and the change in olisthesis seen between these extremes is correlated with the change in disc area and the intervertebral slip angle. Vertical laxity of the affected functional spinal unit resulting from disc degeneration produces laxity in the ligaments and disc anulus, allowing olisthetic motion. Restoration of disc height in turn restores tension to the soft tissues around the disc and results in a spontaneous reduction of the subluxation. Restoration and maintenance of disc height with a spacer or interbody fusion therefore is recommended as a goal in the treatment of spondylolisthesis. When spondylolytic spondylolisthesis involves a posterior column deficiency, additional reconstruction of this column with posterior instrumentation is recommended. Application of the traction radiographic technique in planning for spondylolisthesis reduction is discussed along with the technique of stabilization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Age-related osteoporosis may be associated with inefficient intestinal calcium absorption and bone remodeling. OBJECTIVE: We investigated the pathogenesis of age-related osteoporosis in Chinese women with habitual low calcium intakes. DESIGN: We studied the response of intestinal calcium absorption, calcitropic hormones, and biochemical bone markers to graded dietary calcium deprivation. RESULTS: The osteoporotic subjects (n = 25) had higher urinary calcium excretion (P < 0.05) and lower plasma 1,25-dihydroxyvitamin D concentrations (P < 0.02) than did age-matched control women (n = 25). Parathyroid hormone was not significantly different from that in age-matched control women but was significantly higher than in young women (n = 15, P < 0.05). Fractional 45Ca absorption was approximately 61% in all 3 groups when the diet was unmodified and increased to 71%, 69%, and 68% in the osteoporotic subjects, age-matched control women, and young women, respectively, when dietary calcium was reduced to 300 mg/d. When the osteoporotic women were calcium deprived, serum 1,25-dihydroxyvitamin D failed to increase but urinary calcium excretion persisted. In contrast, supplementation with 1200 mg Ca resulted in a lowering of parathyroid hormone (P < 0.005 compared with the unmodified diet) and 1,25-dihydroxyvitamin D (P < 0.01) and decreased fractional 45Ca absorption (P < 0.01), suggesting that the increased calcium intake was associated with a potent compensatory ability of the intestine and calcitropic hormones to adapt. Calcium supplementation lowered osteocalcin (P < 0.05) but not alkaline phosphatase, which remained elevated in the osteoporotic subjects at all stages. CONCLUSIONS: Elderly osteoporotic women had reduced 1,25-dihydroxyvitamin D production, excessive urinary calcium loss, and high bone turnover. The Chinese women had exceptionally potent intestinal calcium absorption. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Spinal fusion can be complicated by accelerated degeneration of the adjacent segments. Artificial disc replacements have been developed, but results are variable. Successful transplantations of intervertebral disc autografts, fresh allografts, and fresh-frozen allografts-ie, a non-fusion strategy-in which the mobility and stability of the spinal segment were preserved have been done in a primate model. Our aim was to determine the feasibility, safety, and long-term clinical results of disc transplantation in human beings. Methods: Five patients, average age 47 years, with cervical disc herniation underwent transplantation of fresh-frozen composite disc allografts after disc excision. Serial MRI and static and dynamic radiographs were used to monitor the status of the grafts and the sagittal stability and mobility of the segment. Findings: Good union of the graft endplates was seen by the end of 3 months after surgery in all patients. At a minimum follow-up of 5 years, the neurological symptoms of all patients had improved from before surgery levels. No immunoreaction was encountered. There was no olisthesis and only mild degenerative changes of the transplanted discs. All except one of the discs showed preservation of 7.0-11.3 degrees of sagittal motion at the final follow-up. MRI at 5 years showed preservation of hydration in at least two discs. Interpretation: Despite signs of mild disc degeneration, the motion and stability of the spinal unit was preserved after transplantation of fresh-frozen allogenic intervertebral discs in our patients. With further refinements, such transplantations could be an effective treatment for degenerative disc disease. [ABSTRACT FROM AUTHOR]

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2 , many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder., Competing Interests: Competing interests statement:J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron Genetics Center, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical genomic sequencing offered in the Baylor Genetics Laboratory (http://bmgl.com).

Background: The Proximal Femur Maturity Index (PFMI) can be used to assess skeletal maturity on existing whole-spine radiographs without additional radiation. However, the relationship between the PFMI at the initiation of bracing for adolescent idiopathic scoliosis (AIS) and subsequent curve progression remains unknown. This study aimed to investigate the relationship between the PFMI and curve progression, and the predictability of risks to adulthood curve progression and surgical thresholds based on the PFMI grade at brace initiation., Methods: This was a prospective study of 202 patients with AIS who were prescribed underarm bracing according to the Scoliosis Research Society criteria and had good brace-wear compliance. The patients were followed from brace initiation until complete skeletal maturity. Longitudinal data on the coronal Cobb angle and skeletal maturity assessments using Risser staging, Sanders staging, the distal radius and ulna classification, and the PFMI were collected. Each patient was assessed on whether the major curve progressed to ≥40° (adulthood deterioration) and ≥50° (the surgical threshold). Logistic regressions were used to predict probabilities of curve progression to the 2 thresholds, adjusted for factors that were significant in univariate analyses., Results: The PFMI correlated with the other skeletal maturity indices (r s [Spearman rank correlation] = 0.60 to 0.72, p < 0.001 for all). The pre-brace PFMI grade correlated with progression to ≥40° (r rb [rank-biserial correlation] = -0.30, p < 0.001) and to ≥50° (r rb = -0.20, p = 0.005). Based on regression models (p < 0.001) adjusted for the pre-brace major Cobb angle and curve type, brace initiation at PFMI grades 2 and 3 for a curve of ≥30° had predicted risks of 30% (95% confidence interval [CI], 4% to 55%) and 12% (95% CI, 7% to 17%), respectively, for progression to the surgical threshold. Brace initiation at PFMI grade 5 had 0% progression risk., Conclusions: The PFMI can be used for predicting curve progression and prognosticating brace outcomes in AIS. Patients with brace initiation at PFMI grade 4 for a curve of <30° or at grade 5 were unlikely to progress to the adulthood deterioration or surgical threshold. In comparison, skeletally immature patients initiating bracing at a PFMI grade of ≤3 for a major curve of ≥30° had a higher risk of progression despite compliant brace wear., Level of Evidence: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study was funded in part by the Scoliosis Research Society, which did not play a role in the investigation. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H824 )., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.

Study Design: This is a retrospective cohort study., Purpose: This study aims to investigate the risk factors for postoperative distal adding-on in Lenke 1 adolescent idiopathic scoliosis (AIS) and validate the relationship between fusion mass shift (FMS) and postoperative distal adding-on., Overview of Literature: Postoperative distal curve adding-on is one of the complications in AIS. FMS has been proposed to prevent postoperative distal adding-on, which requires further validation from different institutions., Methods: This study included 60 patients with Lenke 1 AIS who underwent selective thoracic fusion surgery. Coronal spinal alignment parameters were analyzed preoperatively, postoperatively, and at the final follow-up. The postoperative FMS was divided into two groups: the balanced group (FMS ≤20 mm) and the unbalanced group (FMS >20 mm). An independent t-test was used to compare quantitative data between groups, and a chi-square test was used for qualitative data. Furthermore, binary logistic regression and receiver operating characteristics curve analyses were used to identify the risk factors for postoperative distal adding-on in AIS., Results: At 2-year follow-up, the unbalanced group was more likely to have adding-on (17 of 24 patients) than the balanced group (six of 36 patients; p<0.001). Twenty-three patients with distal adding-on had significantly greater preoperative and postoperative lower instrumented vertebrae (LIV) rotation, FMS, and FMS angle (FMSA) than those without postoperative distal adding-on. Binary logistic regression analysis selected three independent risk factors for adding-on incidence after surgery: FMS (odds ratio [OR], 1.115; 95% confidence interval [CI], 1.049-1.185; p<0.001), FMSA (OR, 1.590; 95% CI, 1.225-2.064; p<0.001), and postoperative LIV rotation (OR, 6.581; 95% CI, 2.280-19.000; p<0.001)., Conclusions: Achieving a balanced fusion mass intraoperatively is important to avoid postoperative distal adding-on, with FMS of <20 mm and FMS angle of <4.5°. Furthermore, correcting LIV rotation helps to decrease the incidence of postoperative distal addingon.

Background: The sacrum plays an important role in sagittal balance of the spine, whereas the exact association between sacral parameters, specifically the sacral table angle (STA) and spinopelvic parameters has been only scarcely assessed. It aims to investigate the correlations between the sacral parameters and spinopelvic sagittal alignment parameters in healthy adults., Methods: A cohort of 142 Northern Chinese healthy adults between 18 and 45 years old were recruited between April 2019 and March 2021. Full-spine standing X-ray films were performed for every volunteer. The sacral parameters were measured: sacral table angle (STA), sacral inclination (SI) and sacral slope (SS). The spinopelvic sagittal alignment parameters included: pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis and the apex of lumbar lordosis (LLA). The correlations analysis, as well as the linear regression analysis, were performed between STA, SI and the spinopelvic parameters., Results: An equation 'STA = SI + 90 - SS' was revealed to represent the interrelationships between STA, SI and SS. STA was statistically correlated with PI (r s  = - 0.693), PT (r s  = - 0.342), SS (r s  = - 0.530), LL (r s  = 0.454), and LLA (r s  = 0.438). SI correlated with STA (r s  = 0.329), PT (r s  =  - 0.562), SS (r s  =  - 0.612) and LL (r s  = 0.476). Simple linear regression analysis also verified the correlation between STA and PI (y = - 1.047x + 149.4), SS (y = - 0.631x + 96.9), LL (y = 0.660x - 117.7), LLA (y = 0.032x + 0.535), and SI (y = 0.359x + 8.23)., Conclusion: The equation 'STA = SI + 90 - SS' indicates the exact geometric relationship between STA, SI and SS. The sacral parameters, both STA and SI, correlate to the spinopelvic sagittal alignment parameters in healthy adults. The linear regression analysis results also give predictive models for spinopelvic sagittal alignment parameters based on the invariant parameter STA, which are helpful for surgeons in designing an ideal therapeutic plan., (© 2023. The Author(s).)

Objectives: To improve our understanding of patients' perspectives regarding: (1) the decision-making and prehabilitation before lumbar spinal stenosis (LSS) surgery and (2) their postoperative experiences., Design: Qualitative research with semi-structured interviews., Setting: General community., Participants: Individuals who received (N=10) and who did not receive (N=15) prehabilitation before LSS surgery were recruited at the 6-month postoperative follow-up (8 females; average age: 67.7±6.7 years) by purposive sampling. Additionally, 1 participant invited her daughter to accompany her in an interview., Interventions: Not applicable., Main Outcome Measures: Concerns and experiences of patients with LSS regarding prehabilitation and recovery after spine surgery., Results: Thematic analysis was conducted to identify 4 themes inductively: (1) sources of information about LSS surgery; (2) factors affecting the surgical decision-making; (3) attitudes toward prehabilitation; and (4) postoperative recovery. All participants desired to have more preoperative education to inform their surgical decision-making. There were mixed opinions regarding the perceived benefits of prehabilitation because some individuals hesitated to participate in prehabilitation because of their symptoms, or the cost or time of traveling. Many participants expected some or even complete relief of LSS-related symptoms after surgery. However, not all participants experienced the expected postoperative improvements. Some participants only experienced temporary symptomatic relief, while others experienced new postoperative symptoms. Patients generally found that postoperative exercises taught by physiotherapists were useful although their compliance decreased over time., Conclusions: Our study highlights the need for better preoperative LSS education. Because face-to-face prehabilitation or postoperative rehabilitation may not be feasible for all patients, future studies should explore whether online-based prehabilitation or postoperative rehabilitation may benefit certain patient subgroups., (© 2022 The Authors.)

Background: For growing patients, it is ideal to have a growth plate visible in routine radiographs for skeletal maturity assessment without additional radiation. The proximal femoral epiphyseal ossification is in proximity to the spine; however, whether it can be used for assessing a patient's growth status remains unknown., Methods: Two hundred and twenty sets of radiographs of the spine and the left hand and wrist of patients with idiopathic scoliosis were assessed for skeletal maturity and reliability testing. Risser staging, Sanders staging (SS), distal radius and ulna (DRU) classification, the proximal humeral ossification system (PHOS), and the novel proximal femur maturity index (PFMI) were used. The PFMI was newly developed on the basis of the radiographic appearances of the femoral head, greater trochanter, and triradiate cartilage. It consists of 7 grades (0 to 6) associated with increasing skeletal maturity. The PFMI was evaluated through its relationship with pubertal growth (i.e., the rate of changes of standing and sitting body height [BH] and arm span [AS]) and with established skeletal maturity indices. Longitudinal growth data and 780 corresponding spine radiographs were assessed to detect peak growth using receiver operating characteristic (ROC) curve analysis., Results: The PFMI was found to be correlated with chronological age (τ b = 0.522), growth rates based on standing BH (τ b = -0.303), and AS (τ b = -0.266) (p < 0.001 for all). The largest growth rate occurred at PFMI grade 3, with mean standing BH growth rates (and standard deviations) of 0.79 ± 0.44 cm/month for girls and 1.06 ± 0.67 cm/mo for boys. Growth rates of 0.12 ± 0.23 cm/mo (girls) and 0 ± 0 cm/mo (boys) occurred at PFMI grade 6, indicating growth cessation. Strong correlations were found between PFMI gradings and Risser staging (τ b = 0.743 and 0.774 for girls and boys), Sanders staging (τ b = 0.722 and 0.736, respectively), and radius (τ b = 0.792 and 0.820) and ulnar gradings (τ b = 0.777 and 0.821), and moderate correlations were found with PHOS stages (τ b = 0.613 and 0.675) (p < 0.001 for all). PFMI gradings corresponded to as young as SS1, R4, U1, and PHOS stage 1. Fair to excellent interrater and intrarater reliabilities were observed. PFMI grade 3 was most prevalent and predictive for peak growth based on ROC results., Conclusions: The PFMI demonstrated clear pubertal growth phases with satisfactory reliability. Grade 3 indicates peak growth and grade 6 indicates growth cessation., Clinical Relevance: The use of PFMI can benefit patients by avoiding additional radiation in skeletal maturity assessment and can impact current clinical protocol of patient visits. PFMI gradings had strong correlations with SS, DRU gradings, and Risser staging, and they cross-referenced to their established grades at peak growth and growth cessation. PFMI may aid in clinical decision making., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/G875 )., (Copyright © 2022 The Authors. Published by the Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Purpose: Oswestry Disability Index (ODI) was established by Fairbank in 1989 to assess functional disabilities in low back pain (LBP). It was last updated in 2019 as ODI version 2.1b (ODI AU&#95;2.1b). ODI was first translated into Simplified Chinese Oswestry Disability Index (CODI) in 2008 by Lue. The construct validity, internal consistency, level of agreement and the floor and ceiling effects of CODI were found unclear by Yao in 2016. This study will verify how well the adapted Cantonese-Hong Kong Oswestry Disability Index version 2.1b (HKCODI) aligns with ODI AU&#95;2.1b in the Southern Chinese population., Methods: The translation of ODI AU&#95;2.1b was performed according to guidelines from MAPI Research Trust and American Association of Orthopaedic Surgeons. Psychometric properties of HKCODI were tested statistically by Pearson's correlation, Cronbach's Alpha and Intraclass  Correlation  Coefficient (ICC)., Results: A total of 200 subjects (109 males, 91 females) aged from 15 to 85 (mean age = 58.91) with LBP scored from 3/10 to 10/10 in the Visual Analogue Scale (VAS) were recruited in the Occupational Therapy Department of a tertiary referral center. HKCODI demonstrated strong construct validity in comparing with Hong Kong Roland-Morris Disability Questionnaire (HKRMDQ) (r = 0.666, p = 0.000), Short Form Health Survey (SF-36)  Physical Composite Summary (- 0.700, p = 0.000) and VAS (0.487, p = 0.000). Excellent internal consistency and test-retest reliability were confirmed with Cronbach's Alpha of 0.997 and ICC of 0.993 at 95% confidence level., Conclusion: Cross-cultural adaptation of ODI AU&#95;2.1b has been translated and validated as   HKCODI and Item-8 (Sex Life) was suggested to skip for patient older than 60. HKCODI is a fully self-administered and highly reliable tool in assessing the functional disability of patients with LBP in the Southern Chinese population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Congenital scoliosis (CS) is a lateral curvature of the spine resulting from congenital vertebral malformations (CVMs) and affects 0.5-1/1000 live births. The copy number variant (CNV) at chromosome 16p11.2 has been implicated in CVMs and recent studies identified a compound heterozygosity of 16p11.2 microdeletion and TBX6 variant/haplotype causing CS in multiple cohorts, which explains about 5-10% of the affected cases. Here, we studied the genetic etiology of CS by analyzing CNVs in a cohort of 67 patients with congenital hemivertebrae and 125 family controls. We employed both candidate gene and family-based approaches to filter CNVs called from whole exome sequencing data. This identified 12 CNVs in four scoliosis-associated genes ( TBX6 , NOTCH2 , DSCAM , and SNTG1 ) as well as eight recessive and 64 novel rare CNVs in 15 additional genes. Some candidates, such as DHX40 , NBPF20 , RASA2 , and MYSM1 , have been found to be associated with syndromes with scoliosis or implicated in bone/spine development. In particular, the MYSM1 mutant mouse showed spinal deformities. Our findings suggest that, in addition to the 16p11.2 microdeletion, other CNVs are potentially important in predisposing to CS.

This cross-sectional study aims to investigate the relationship between the simplified olecranon, simplified digital, and distal radius and ulna (DRU) classifications, and whether they can aid in more comprehensive maturity assessment together. Left hand and wrist and lateral elbow radiographs from pediatric patients were assessed using the three skeletal maturity indices. The association between maturity indices was investigated using Goodman and Kruskal's gamma, and by mapping of individual grades based on chronological age. Specific maturity grades, at which peak height velocity (PHV) occurs as previously identified, were based upon to explore how the three systems interact. A total of 114 patients (63.2% girls) were studied. Correlations and associations between the three maturity parameters were significant (all at P < 0.001). Mapping revealed uneven spans and coverage of different periods by each index. Olecranon stage 1 coincided with R3 (for girls), R4 (for boys), U3, and SS1. Olecranon stage 5 occurred as early as R7, U6, and SS4. Upon elbow fusion, the simplified digital (SS5-SS8) and DRU (R8-R11 and U7-U9) classifications can be used for assessment until maturity. The inter-relationship of the simplified hand, wrist, and olecranon methods indicates their combined use. DRU grades can be used in growth periods which are less well covered. Prepubertal and growth acceleration phase of pubertal growth spurt can best be assessed by both the simplified olecranon (stages 1-3) and DRU classifications (R1-R5 and U1-U4). All three indices are required during PHV. For post-PHV, DRU (R8-R11 and U7-U9) and simplified digital method (SS5-SS8) complement each other for assessment until skeletal maturity., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Congenital scoliosis (CS) is a spinal deformity present at birth due to underlying congenital vertebral malformation (CVM) that occurs during embryonic development. Hemivertebrae is the most common anomaly that causes CS. Recently, compound heterozygosity in TBX6 has been identified in Northern Chinese, Japanese, and European CS patient cohorts, which explains about 7%-10% of the affected population. In this report, we recruited 67 CS patients characterized with hemivertebrae in the Southern Chinese population and investigated the TBX6 variant and risk haplotype. We found that two patients with hemivertebrae in the thoracic spine and one patient with hemivertebrae in the lumbar spine carry the previously defined pathogenic TBX6 compound heterozygous variants. In addition, whole exome sequencing of patients with CS and their family members identified a de novo missense mutation (c.G47T: p.R16L) in another member of the T-box family, TBXT. This rare mutation compromised the binding of TBXT to its target sequence, leading to reduced transcriptional activity, and exhibited dominant-negative effect on wild-type TBXT. Our findings further highlight the importance of T-box family genes in the development of congenital scoliosis., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: There are no clear indicators for predicting return to work for patients with chronic low back pain (LBP). We aim to report the outcomes of a 14-week multidisciplinary programme targeting patients with chronic LBP who failed conventional physiotherapy to provide functional rehabilitation. Also, this study will identify factors predicting successful return to work (RTW)., Methods: A collected cohort of patients with chronic LBP was consecutively enrolled into the programme from 1996 to 2014. All recruited patients failed to RTW despite at least 3 months of conservative treatment. Patient underwent weekly multidisciplinary sessions with physiotherapists, occupational therapists and clinical psychologists. Patient perceived function was considered the primary outcome of the programme. Patients were assessed for their sitting, standing and walking tolerance. Oswestry Disability Index (ODI) and Spinal Function Sort Score (SFSS) were used to assess patient perceived disability., Results: One hundred and fifty-eight patients were recruited. After the programme, statistically significant improvement was found in ODI (47.5 to 45.0, p = 0.01) and SFSS (98.0 to 109.5, p <  0.001). There was statistically significant improvement (p <  0.01) in sitting, standing, walking tolerance and straight leg raise tests. 47.4% of the patients were able to meet their work demand. Multivariate logistic regression model (R 2  = 59.5%, χ 2 (9) = 85.640, p <  0.001) demonstrated that lower initial job demand level and higher patient-perceived back function correlated with greater likelihood of returning to work., Conclusion: The results of this study may support the use of this multidisciplinary programme to improve patient function and return to work.

Purpose: This study aimed to evaluate the diagnostic aptitude of a modified Adams forward bending test (MAFBT), which addresses the coupling phenomenon of axial rotation with reference to the side-bending movement. Also, this evaluation was facilitated by the introduction of our rotational flexibility index (RFI)., Methods: Thirty-two female and eight male AIS patients were included in this study from a single institution. In the MAFBT, subjects were asked to bend to the convex side of the curve in the forward bending position. Scoliometric measurements were done during the AFBT and MAFBT. Utilizing anteroposterior standing plain radiographs curve flexibility indices were calculated. The diagnostic aptitude of the MAFBT was evaluated based on the receiver operating characteristic (ROC) curves and area under the curve (AUC). The RFI was also assessed, which considered AFBT and MAFBT parameters as a specified function., Results: Significant correlations were noted between the Cobb angle and AFBT (p = 0.005), fulcrum bending and the MAFBT (p = 0.0001), side-bending and MAFBT (p = 0.0001). There were significant positive correlations between rotational flexibility as based on fulcrum bending radiograph to that of the RFI (r = 0.4, p = 0.036) and side-bending technique (r = 0.4, p = 0.008). Based on ROC analyses (AUC range 0.7-0.8), the MAFBT demonstrated high specificity and sensitivity rates for flexible and rigid curves, respectively., Conclusions: This is the first study to report that the MAFBT is a simple and reliable test for the clinical assessment of rotational flexibility in AIS patients. The study further noted that the novel RFI has clinical utility in the assessment of AIS.

Background: There is no recommended standard for positioning of a mouse for radiographic assessment of the spine. This is necessary to have reproducible radiographic data and avoid false positive results. The objective of this study was to investigate the impact of various postures on Cobb angle measurements and to set up a positioning standard for imaging mouse spines., Methods: This study was conducted in three parts. Firstly, we identified the problem of lack of posture standardization for radiographs. We collected 77 C57BL/6 J mice for spine radiographs and found a scoliosis prevalence of 28.6% with large variations in curve magnitude. Secondly, 24 C57BL/6 J mice underwent 4 consecutive weekly radiographs and observed high variations (relative standard deviation: 125.3%) between radiographs. Thirdly, we collected another 82 C57BL/6 J mice and designed 14 different postures that could take place during imaging. These postures were related to curling of the limbs, and head, pelvic and tail tilting., Results: The results showed that head and pelvic tilting significantly affects the curve magnitude with effect size (Glass's delta) over 1.50. Avoiding these incorrect positions during radiographs is warranted. The standard recommended posture for mouse imaging entails positioning the snout, interorbital space, neck and whole spine in one line, and with the limbs placed symmetrical to the trunk, whilst avoiding stretching the body of the mouse., Conclusions: Our work exemplified the importance of standard protocol during imaging when using an animal model in the scoliosis study. We recommend utilizing this standard in studying various disorders of the spine to avoid technical causes for the appearance of a curve.

Hypothesis: Fusing shorter than the last touched vertebra (LTV) is a safe approach in flexible main thoracic (MT) adolescent idiopathic scoliosis (AIS) curves., Methods: This was a prospective study on consecutive AIS patients surgically treated with selective fusion of the MT curve. Fusion-level selection was based on the fulcrum-bending radiograph method. Patients were grouped based on the position of the lowest instrumented vertebra as proximal to the LTV (proxLTV, n = 43), at the LTV (atLTV, n = 45), and distal to the LTV (distLTV, n = 21)., Results: A total of 109 patients were included in the study. Preoperatively, the distLTV group had greater lumbar Cobb angle, lumbar apical translation, and less flexibility in the MT curve. At 2-year follow-up, the groups did not differ in MT curve correction, but the distLTV had larger lumbar Cobb angle, more apical translation, and worse coronal balance. Distal adding-on was observed in 11 patients (26%) in the proxLTV group, four patients (9%) in the atLTV group, and one patient (5%) in the distLTV group (p = 0.031). Adding-on was associated with younger patients and lower Risser grade at the time of surgery but not with any other radiographic parameter. No differences in SRS-22r scores were observed between the groups., Conclusions: Proximal fusion carries the risk of adding-on, but leaving unfused segments in the lower spine increases the potential for compensatory mechanisms to improve spinal and truncal balance. In mature patients with a flexible MT curve, surgeons may consider fusion at or cranial to the LTV.

Background Context: There is often discrepancy between clinical presentation and lumbar magnetic resonance imaging (MRI) findings., Purpose: The purpose of this study was to assess the relationship of high-intensity zones (HIZs) on MRI with low back pain (LBP), sciatica, and back-related disability., Study Design: Cross-sectional, population-based Southern Chinese cohort study., Patient Sample: Of 1,414 possible participants, data from 1,214 participants (453 males, 761 females; mean age of 48.1±6.3 years) were included., Outcome Measures: Presence of single-level, homogeneous multilevel (same type HIZs of morphology and topography) and heterogeneous multilevel (mixed type HIZs of morphology and topography) HIZs and other MRI phenotypes were assessed at each level with T2-weighted 3T sagittal MRI of L1-S1. Associations with LBP, sciatica and Oswestry Disability Index were correlated with HIZ profiles., Results: In all, 718 individuals had HIZs (59.1%). Disc degeneration/displacement were more prevalent in HIZ individuals (p<.001). HIZ subjects experienced prolonged severe LBP more frequently (39.6% vs. 32.5%; p<.05) and had higher Oswestry Disability Index scores (10.7±13.7 vs. 8.9±11.3; p<.05). Posterior multilevel HIZ were significantly associated with prolonged severe LBP (OR: 2.18; 95% CI:1.42-3.37; p<.05) in comparison to anterior only, anterior/posterior or other patterns of HIZ. Multilevel homogeneous or heterogeneous HIZs were significantly associated with prolonged, severe LBP (OR: 1.53-1.57; p<.05). Individuals with homogeneous HIZs had a higher risk of sciatica (OR: 1.51, 95% CI: 1.01-2.27; p<.05)., Conclusions: This is the first large-scale study to note that lumbar HIZs, and specific patterns therein, are potentially clinically-relevant imaging biomarkers that are independently and significantly associated with prolonged/severe LBP and sciatica. HIZs, especially homogenous multilevel HIZ, should be noted in the global pain imaging phenotype assessment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objectives: To assess how the thoracic kyphosis affects the ability of the fulcrum bending radiograph (FBR) to predict the coronal thoracic curve correction., Methods: A retrospective study of prospectively collected data was conducted of 107 consecutive patients with thoracic adolescent idiopathic scoliosis (AIS) treated with a standard screw-fixation protocol. Radiographic variables were assessed preoperatively and at 2-year follow-up. Curve flexibility was determined based on the FBR and the Fulcrum Bending Flexibility Index (FBCI). Radiographic variables included preoperative Cobb angle, T5-T12 kyphosis, T12-S1 lordosis, sagittal vertical axis, list, T1-T12 length, truncal shift, and radiographic shoulder height. Patients were also categorized as hypo-, normo-, or hyperkyphotic., Results: Based on multivariate modeling, an increase in FBR Cobb angle and thoracic kyphosis were significantly associated with an increase in FBCI (increased mismatch between the FBR and postoperative Cobb angles) at 2-year follow-up ( P < 0.001). In patients with hyperkyphosis, a longer instrumented length existed despite similar curve size and shorter curve length than the hypo- and normokyphotic groups. Based on these findings, we developed a new predictive postoperative curve correction index, known as the Multiprofile Flexibility Index (MFI)., Conclusions: Our results show that an increase in preoperative thoracic kyphosis is associated with an increased difference between the preoperative coronal curve flexibility and the postoperative coronal curve correction. Our findings broaden the understanding of curve flexibility and indicate that selection of fusion levels may need to take into consideration the sagittal profile to improve clinical decision making and optimize outcome., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Study Design: Cadaveric biomechanical with imaging analysis., Objective: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration., Summary of Background Data: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration., Methods: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis., Results: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw., Conclusions: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Lumbar disc-displacement, Modic changes (MCs), and UTE Disc Sign (UDS) on MRI are clinically relevant spinal phenotypes that can lead to sciatica/LBP. Not all degenerated discs result in disc-displacement, MCs and UDS, suggesting varied etiologies. Spinopelvic parameters have been implicated in various spinal disorders. Pelvic incidence (PI) is "fixed parameter" since skeletal maturity. No study has addressed disc-displacement, MCs and UDS in context of spinopelvic parameters. Therefore, the aim of study was to determine if spinopelvic parameters are associated and predict clinically-relevant MRI-phenotypes. One hundred and eight population-based subjects (mean age: 52.3 years) were recruited. Spondylolisthesis and scoliosis individuals were excluded. Lumbar lordosis (LL), PI, sacral slope (SS), and pelvic tilt (PT) were assessed on lateral plain radiographs. Disc degeneration was assessed and summated, and presence or not of disc-displacement and MCs were noted on T2W MRI. UDS was detected on UTE. Following exclusion criteria, 95 subjects were assessed. Disc-displacement (82.1%), MCs (52.6%), and UDS (37.9%) were associated with lower PI, SS, LL, and LL/PI index. On multivariate analyses, lower PI was significantly related to development of these MRI phenotypes (adjusted OR range:0.95-0.92; P  < .05), with critical PI value of 42° or lower exhibiting fourfold increase risk of combined phenotypes ( P = .020). Of UDS discs, 39.3% had adjacent MCs and 83.6% had disc-displacement. 87.5% of MC had directly adjacent UDS. The first study to note that PI may "predict" the development of disc-displacement, MCs and UDS, suggesting potential sub-variants and mechanistic susceptibility that may be grounded in spinopelvic evolution. An "evolutionary etiological pathway" of spinal phenotype development is proposed., Competing Interests: The authors have no conflict of interest., (© 2020 The Authors. JOR Spine published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.)