Aims. To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing. Methods. Two independent reviewers performed a comprehensive literature search in PubMed, Ovid, Web of Science, Scopus, and Cochrane Library to obtain all published information about the effectiveness of bracing in achieving curve regression in AIS patients. Search terms included “brace treatment” or “bracing,” “idiopathic scoliosis,” and “curve regression” or “curve reduction.” Inclusion criteria were studies recruiting patients with AIS undergoing brace treatment and one of the study outcomes must be curve regression or reduction, defined as > 5° reduction in coronal Cobb angle of a major curve upon bracing completion. Exclusion criteria were studies including non-AIS patients, studies not reporting p-value or confidence interval, animal studies, case reports, case series, and systematic reviews. The GRADE approach to assessing quality of evidence was used to evaluate each publication. Results. After abstract and full-text screening, 205 out of 216 articles were excluded. The 11 included studies all reported occurrence of curve regression among AIS patients who were braced. Regression rate ranged from 16.7% to 100%. We found evidence that bracing is effective in achieving curve regression among compliant AIS patients eligible for bracing, i.e. curves of 25° to 40°. A similar effect was also found in patients with major curve sizes ranging from 40° to 60° when combined with scoliosis-specific exercises. There was also evidence showing that a low apical vertebral body height ratio, in-brace correction, smaller pre-brace Cobb angle, and daily pattern of brace-wear compliance predict curve regression after bracing. Conclusion. Bracing provides a corrective effect on scoliotic curves of AIS patients to achieve curve regression, given there is high compliance rate and the incorporation of exercises. Cite this article: Bone Joint J 2024;106-B(3):286–292

Introduction. Previous work has shown that C57BL/6 mice develop scoliosis when rendered bipedal. Our previous work suggested that tamoxifen (TMX) might change the natural course of scoliosis when administered before scoliotic curves develop. We analysed whether the incidence of scoliosis or the magnitude of curves may be decreased by the administration of tamoxifen after curves are observed. Methods. 20 female, 3-week-old C57BL/6 mice underwent amputations of forelimbs and tails at 3 weeks, 18 of which were included in analyses. Posteroanterior scoliosis radiographs were obtained at week 20, and scoliotic curves were recorded. After week 20, all mice received 10 mg TMX per L of daily water supply for 20 weeks. The course of deformities in this group (week 20 group) was compared with that of previous study groups (receiving TMX from week 3; week 3 group). Results. At week 20, overall, upper thoracic (UT), thoraco-lumbar (TL), and double curve scoliosis rates were similar in both groups, but the thoracic (T) scoliosis rate was lower in the week 3 group. At week 40, although T, TL, and double curve scoliosis rates were similar between groups, overall rate and the rates of UT scoliosis were significantly lower in week 3 group (table). We recorded no significant change of curve rates in week 20 group apart from the TL rate, which showed a significant increase (p=0·025). Mean Cobb angles were similar in both study groups (p>0·05) at 20 and 40 weeks. Conclusions. This study has shown that TMX administered after scoliotic changes are observed seems to be less effective compared with prior TMX protocol in C57BL/6 mice model. This information is important for the planning of possible pharmacological intervention in human beings

Pedicle screw constructs (PSC) in scoliosis are a recently established and widely accepted method of managing scoliotic curves posteriorly. There is a perceived improved coronal and rotational correction when compared to other posterior only constructs. With continued use of this method, the authors and deformity surgeons in general have become aware of persistent thoracic hypokyphosis. This review of 3 years of scoliosis cases using PSC looks at four different implant strategies utilised to manage this problem and our current practice. These strategies were:. All titanium 5.5 mm rod diameter (Expedium, Depuy spine). All titanium 5.5 mm rod diameter with periapical washers (Expedium, Depuy spine). All titanium 6.0 mm rod diameter (Pangea, Synthes). Titanium pedicle screws with 5.5 mm diameter cobalt chrome rods (Expedium Depuy spine). We have reviewed our outcomes with these strategies with respect to thoracic hypokyphosis. Strategy 1 had the highest rate of hypokyphosis on postoperative radiographs. Strategy 4 seems to have the best correction of coronal and sagittal plane abnormality post operatively. As a consequence, our current practice is the use of titanium pedicle screws and 5.5 mm diameter cobalt chrome rods when managing scoliosis with a pedicle screw construct

Much debate exists over the value of exercise therapy for treating adolescent idiopathic scoliosis (AIS). This study aims to address the current evidence. An extensive search was carried out using the common medical databases, limiting results to clinical trials in English involving humans with defined outcome measures. 155 papers were identified and after applying strict inclusion criteria 12 papers remained for further analysis. These included 9 prospective cohort trials, 2 retrospective cohort trials and one case series. No randomised controlled trials were identified. Although all of the papers concluded an improvement in scoliotic curve after exercise therapy, not one of the papers had reliable methods or results to validate their conclusions. Identified shortcomings included, poor compliance with outpatient exercise regimes with no clear indication of who assessed for curve improvement, how it was assessed or what experience they had, nor was observer error for Cobb angle measurement taken into account. Additionally only a few of the studies had sound statistical analysis and no study could comment on whether the improvements seen were maintained after the exercise regime. Four previous systematic reviews have been performed finding favourable results for exercise therapy, but these were written by authors involved in the original research, adding significant reviewer bias. This systematic review has revealed only poor and low level evidence supporting the use of exercise therapy for treating AIS. Well designed controlled trials with randomisation are required to validate exercise therapy as an effective treatment option and as an appropriate use of NHS funds

Introduction. Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children, and its cause is unknown. Recently, researchers have traced a defect in the gene CHD7 to AIS. CHD7 encodes for a chromodomain helicase of the DNA-binding domain protein family and is thought to have a crucial role in many basic cellular functions. However, the functional role of CHD7 in AIS is still elusive. In this study, we investigated the potential pathogenic effect of gene defects in CHD7 in vivo by evaluating their effect on spine formation and development in zebrafish. Methods. To investigate the function of the CHD7 encoded protein, we generated an antisense morpholino oligonucleotide against the CHD7 gene to disrupt the translation of the gene transcripts and knockdown the levels of its protein. The morpholino was injected into single-cell stage zebrafish embryos. The injected fish were allowed to develop and were then assessed for distinct phenotypes reminiscent of scoliosis by histological stains. Results. Knockdown of CHD7 resulted in a spectrum of ocular and heart anomalies. We noted that 26% of the zebrafish morphants exhibited curvature of the body axis at early stages. Histological stains of the vertebrae at later stages revealed that the spine of the zebrafish morphant had abnormal kinks rather than scoliotic curves. These defects were accompanied by reduced vertebral mineralisation around the kink area. The CHD7 morphant also showed severe cranial nerve abnormalities and had missing or malformed otolith—a part of the vestibular system analogous to the human ear. Conclusions. Our findings indicate a key role of CHD7 in eye, heart, and ear development but not in the onset of skeletal deformities as observed in scoliosis. Our results are similar to the congenital abnormities associated with CHD7 mutations in the CHARGE syndrome. Acknowledgments. This study is supported by the Yves Cotrel Fondation

Introduction. The response of the intervertebral disc to asymmetric forces may accelerate degeneration through changes in the matrix. Macroscopically, the disc sustains structural changes that may play a part in the progression of a scoliotic curve. Molecularly, disc degeneration is the outcome of the action of matrix metalloproteases (MMPs), members of a family of enzymes that bring about the degradation of extracellular matrix components. In this study we measured in vivo the expression of MMPs in a rat scoliotic intervertebral disc and studied the effect of the degree of the deformity on their production. Methods. Asymmetric forces were applied in the intervertebral disc between the ninth and tenth vertebrae at the base of a rat tail with the use of a mini Ilizarov external fixator, under anaesthesia. Animals were categorised into three groups according to the degree of the deformity. In group I, the deformity that was applied on the intervertebral disc was 10°, in group II 30°, and in group III 50°. All the animals used were female Wistar rats before adulthood, to take into account the effect of growth for the study of intervertebral disc changes. The intact intervertebral discs outside the fixator were used as controls. After the rats' death on day 35, the tails were prepared and analysed with an immunohistochemical protocol for chromogenic detection and location of MMPs 1 and 12 in tissue sections of the intervertebral discs. Results. We recorded an increase of the concentration of the MMPs in all groups compared with controls. The quantity of the MMPs increased as the degree of the deformity progressed. MMPs were detected mainly in fibrocartilage cells of the degenerative part, which were formed as result of the compression forces. We detected a differentiation of a large number of disc cells into chondrocytes at the transitional zone of the intervertebral disc adjacent to the vertebral end plates. Conclusions. The application of asymmetric forces on the intervertebral discs of a rat tail results in an increase of MMP expression in the disc cells. The amount of MMPs produced is proportional to the degree of the deformity and has an asymmetrical pattern of distribution into the intervertebral disc

AIS is present in 3–5% of the general population. Large curves are associated with increased pain and reduced quality of life. However, no information is available on the impact of smaller curves, many of which do not reach secondary care. The objective of this project was to identify whether or not there is any hidden burden of disease associated with smaller spinal curves. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a population-based birth cohort that recruited over 14,000 pregnant women from the Bristol area between 1991–1992 and has followed up their offspring regularly. At aged 15 presence or absence of spinal curvature ≥6degrees was identified using the validated DXA Scoliosis Measure in 5299 participants. At aged 18 a structured pain questionnaire was administered to 4083 participants. Chi-squared was used to investigate any association between presence of a spinal curve at aged 15 and self-reported pain at aged 18 years. Sensitivity analyses were performed by rerunning analyses after excluding those who were told at aged 13 they had a spinal curve (n=27), and using a higher spinal curve cut-off of ≥10degrees. Full data was available for 3184 participants. Of these, 56.8% were female, and 4.2% non-white reflecting the local population. 202 (6.3%) had a spinal curve ≥6degrees and 125 (3.9%) had a curve ≥10degrees. The mean curve size was 12degrees. 140/202 (69.3%) had single curves, and 57.4% of these were to the right. In total 46.3% of the 3184 participants reported aches and pains that lasted for a day or longer in the previous month, consistent with previous literature. 16.3% reported back pain. Those with spinal curves ≥6degrees were 42% more likely to report back pain than those without (OR 1.42, 95%CI 1.00 to 2.02, P=0.047). In addition, those with spinal curves had more days off school, were more likely to avoid activities that caused their pain, were more likely to think that something harmful is happening when they get the pain, and were more afraid of the pain than people without spinal curves (P<0.05). Sensitivity analyses did not change results. We present the first results from a population-based study of the impact of small spinal curves and identify an important hidden burden of disease. Our results highlight that small scoliotic curves that may not present to secondary care are nonetheless associated with increased pain, more days off school and avoidance of activities

Introduction. Autonomic nerve system (ANS) regulates intercostal vascular nutrition (internal mammary artery), and its pathological status leads to developmental asymmetry of the trunk and rib cage, and consequently producing scoliotic deformity of the spine. The aim of this study is to investigate the possible causation of idiopathic scoliosis in development abnormalities of ANS. Methods. We evaluated samples taken from 12 patients with idiopathic scoliotic deformities and a control set of three patients without scoliotic deformity. We examined the samples of autonomic nerves taken from convexity and concavity of the scoliotic deformity during the patients' surgical correction by the transthoracic approach. We used the electronmicroscopic method to analyse samples, and the morphometric method for statistical evaluation. Results. Evaluation of the samples taken from scoliotic convexity and the control samples of non-scoliotic patients showed normal findings in autonomic nerve structures. We detected significant morphological changes in all scoliotic samples taken from concavity. These changes were mostly in myelin vaginas with abnormalities and compression of the axon fibre, massive lesion and separation of the myelin sheath, vacualisation of cytoplasma of the Schwann cells, and condensation of the cytoblast. By morphometric measurements we found 23·71% of myelinised nerve fibres (MNF), 12·21% of unmyelinised nerve fibres (UNF), and 5·0% of Schwann cells (SC) in samples taken from scoliotic convexity, and 29·9% of MNF, 19·9% of UNF, and 16·7% of SC in control non-scoliotic samples. We recorded 17·36% of MNF, 5·82% of UNF, and 5·27% of SC in samples taken from concavity. Conclusions. We noted abnormalities in structure of ANS in concave side of scoliotic curves, and statistically significant differences between both sides of scoliotic deformity (convexity and concavity). Furthermore, we recorded discrepancies between scoliotic samples and non-scoliotic control samples. The abnormalities, mostly in the myelinated fibres, might be originated by the primary genetic lesion and thus could affect the development of scoliosis. The abnormalities of ANS can produce changes in internal mammary artery, and consequently can lead to the abnormal blood supply of vertebrae as well as anterior wall chest. These abnormalities of ANS could lead to the scoliotic origin in growing spine

Introduction. Calmodulin probably has a regulatory role in muscle contraction and its antagonism may decrease the magnitude and progression of scoliosis. A separate study has shown that tamoxifen (TMX), a known antagonist, is effective in altering the natural history in an avian model; however, whether the same effect is conceivable in mammals is unknown. We aimed to analyse whether the natural course of scoliosis in mice may be altered by the administration of TMX. Methods. 60 female, 3-week-old, C57BL/6 mice underwent amputations of forelimbs and tails. 57 mice were assigned to three groups: control group, no medications; TMX group, 10 mg TMX/L drinking water; and combined group, 10 mg TMX plus 10 mg trifluoperazine (TFP)/L drinking water. PA scoliosis radiographs were taken at 20 and 40 weeks and evaluated for presence and magnitude of spinal curves. Results. Four mice were lost to follow-up in the TMX group. Overall scoliosis rate was significantly lower in the TMX group (33%) than in the control (90%) and combined (68%) groups (p=0·001) at week 40. Similarly, upper thoracic scoliosis rate was lower in the TMX group (27%) than in control (74%) and combined (47%) groups (p=0·01). The thoracic scoliosis rate was also lower in the TMX group (7%) group than in control (63%) and combined (26%) groups (p=0·001). Combined drug group had lower thoracic and lumbar Cobb angles (17·50° [□}3·45]) than did the control group (29·40° [□}5·98]; p=0·031). Furthermore, double curve incidence at week 40 was lower in TMX group (12%) than in control (74%) and combined (47%) groups (p=0·001). Triple curve incidence was lower in combined (0%) and TMX (6%) groups than in the control group (15%), but this result was not significant (p=0·167). Conclusions. TMX effectively decreased the incidence and magnitude of the scoliotic curves in C57BL/6 mice scoliosis model. This is a novel finding, and could be very important in opening a pathway for the conservative treatment of idiopathic scoliosis by oral drugs

Introduction. Kyphoscoliosis is defined by a structural lateral curvature of the spine of 10° or more and an excessive thoracic kyphotic curve of 40° or more. Genetic analyses of families in which two or more members had kyphoscoliosis identified a 3·5 Mb area on chromosome 5p containing three genes of the Iroquois (IRX) homeobox family, IRX1, IRX2, and IRX4, which were then sequenced. Methods. Exons and highly conserved non-coding regions (HNCRs) 500 kb upstream and downstream fromIRX1, IRX2, and IRX4 were sequenced in 46 individuals from six families. Selection of these elements was based on PhastCons Placental Mammal Conserved Elements, Multiz Alignment. Single-nucleotide polymorphism (SNP) genotypes and sequence variants were obtained from all individuals. There were 431 SNPs, 61 in IRX4 regions, 80 in IRX2 regions, and 290 in IRX1 regions. 137 SNPs were novel. Mendelian inconsistencies were detected with PEDCHECK (inconsistency rate: 1·4%; missing data: 2·8%). SNPs and individuals with greater than 10% missing rate were excluded. Association analyses (ASSOC [SAGE version 6.0.1]) of the quantitative trait with patient's largest curve, were undertaken on 391 SNPs. Results. Association analyses resulted in 12 SNPs with p values less than 0·025, 11 of which were located upstream and downstream from IRX1. The most significant p value (p=0·000382) was obtained for rs35710183 (table). Multiple variants were found surrounding IRX1. The most prominent is a single base-pair deletion in all affected individuals genotyped in one family. All individuals with kyphoscoliosis and those with scoliotic curves greater than 35° had genotypes differing from the reference (unaffected) genotype for 23 SNPs. Several of these SNPs had significant p values for the association analyses done previously. Conclusions. The phenotype of kyphoscoliosis has been linked to sequence variants that lie within regulatory regions of the IRX homeobox gene family. Further analyses to establish the relevance of these findings will be done through in-vivo and in-vitro assays. The identification of spinal genetic determinants related to axial growth and maturation will help with the understanding of spinal pathology and potentially allow for development of directed therapeutic interventions

Introduction. Forelimb and tail amputations of 3-week-old C57BL/6 mice are known to yield spinal curves similar to adolescent idiopathic scoliosis (AIS). Our previous work showed that tamoxifen produces a significant decrease in severity of these curves. Vertebral osteoporosis was thought to be related to AIS. Interestingly, a histological pilot study has shown that scoliotic mice given tamoxifen were less osteoporotic than were controls. Raloxifene is an oestrogen receptor modulator (SERM) similar to tamoxifen with a more specific effect on bone and is commonly used to treat osteoporosis. We aimed to study and compare the effects of tamoxifen and raloxifene on the rate and magnitude of scoliosis on a C57BL/6 mice model. Methods. 90 female 3-week-old C57BL/6 mice underwent amputations of forelimbs and tails. 78 were available for analysis and were grouped as control (no medications; n=24), TMX group (10 mg tamoxifen/L drinking water; n=30), and RLX group (10 mg raloxifene/L drinking water; n=241). Seven mice from each group (including scoliotic ones) were killed for histological study at week 20 after posteroanterior (PA) scoliosis radiograph examinations. The rest were killed at the end of week 40 after PA radiographs were obtained. Radiographs were assessed for presence and magnitude of spinal curves. Results. Week 20 analysis showed that lower thoracic curve rate (LTr) was higher in RLX group (p=0·029) and thoracolomber rate (TLr) was higher in TMX group (p=0·33) than in the control group. TMX group had higher upper thoracic (UT) curve magnitudes than did the control group (p=0·021). Week analysis showed similar curve rates in all groups. The RLX group had significantly decreased upper (p<0·0001) and lower (p=0·014) thoracic curve magnitudes compared with the control group. The TMX group had significantly lower UT curve magnitudes than did the control group (p=0·014). Conclusions. Raloxifene is shown to be as effective as tamoxifen in decreasing the magnitude of spinal deformities in C57BL/6 mice model. These results suggest that SERMs might be useful to prevent progression of scoliotic curves. Models of higher animals may be warranted

Introduction. Spinal deformations are a deviation of the natural arrangement of forces during growth. Environmental factors play a part in these deviations. The presence of lordosis in the thoracic spine is a causative factor in spinal deformations that needs to be addressed. Most biomechanical models of bracing have a scientific background. Has older knowledge lost its value? In living structures, all processes such as regulation of equilibrium in posture and movement use Newton's law and extended laws of Hooke for conservation of energy, momentum, and angular momentum under control of the central nervous system. Form follows function (phylogenetic and ontogenetic) in the spine as primary engine in movement in animals. The change in function in bipedals is that the coupling mechanism at the thoracolumbar joint now couples a reversed pendulum. Methods. A literature search shows a clear gap in the evolution in science on deformities during 1914–45. In 1792, Van Gesscher postulated two concepts in Observations on Deformations of the Spine (Dutch). First, the optimalisation of the balancing forces in men needs a specific optimum curvature to keep the weight of the head and shoulders above the hips. The second concept was the role of sitting in relation to changes around the discs at the thoracolumbar spine. Girls who read or knitted while sitting developed scoliosis more easily than did others. His extending (by lordosis) corrective corset was used for more than 150 years before plaster became popular. Andry described guidance and correction of growing spines with use of the moulding capability of muscular forces, with exercises and extending corsets (for so-called weak girls). Extension and avoidance of incorrect posture during sitting became a mainstay in orthopaedics (and schools). In 1907, Wullstein described experiments in young dogs to show how forced fiexion produces all characteristics of kyphotic deformities. In 1912, Murk Jansen did a critical review of all available knowledge and his own research in The Physiologic Scoliosis and its causes. Post mortem studies showed anatomical asymmetry in the left and right crura of the diaphragm, which indicated that asymmetric rotational forces in ventilation could induce predominant lateral curves. In-vivo tests show increased thoracolumbar kyphosis if siblings are put in seated positions too frequently and too soon. The stiffening in kyphosis creates a fulcrum to cantilever the opposing rotational forces to lateral curvatures. In experiments in rabbits, lower intrathoracic pressure was shown in the right pleural cavity. Common alertness of parents and teachers was underwritten. Some of this still survives. In progressed scoliosis, Sayre's method of corrective plastering in suspension and Calot's corrections in prone position under anaesthesia and plaster shelves with lordosis in bed became popular. In the Volkmann Hueter principle, the resilience of the deformable structures in the spine were identified–eg, the discs, the apophyses, and the cartilage in joints have a role in spinal deformity. Cobb drew attention to the clinical aspects of scoliosis. Roth provided a comprehensive explanation of how growth is organised and regulated by the oldest organ of animal life: the central nervous system in vertebrates. Between 1960 and 1985, Roth developed his concepts on neurovertebral and neuro-osseous growth relations and the tension-driven incongruence of growth. Roth provided new biological knowledge about how growth seems to support older clinical observations. In animal experiments, mechanical modelling, and radiological studies in scoliosis he stressed the role that growth has in the formation of the spine. A so-called short cord can indeed cause scoliosis. Recent studies with MRI in idiopathic scoliosis confirm this hypothesis. Personal observations In 2008, a study showed that forceful restoration of thoracolumbar lordosis can correct double major scoliotic curves. A consequent thoracolumbar kyphotic curve was found, and recently reproduced. The thoracolumbar lordotic intervention brace technique showed promising results. It relied on the older techniques, leaving only the fear for lordosis brought by Dickson. In personal observations, the presence of neuromuscular tightness or tension also present in progressive scoliosis as representatives of deforming and protective forces. Conclusions. Previous knowledge depicts spinal growth as result of a combination of neuro-osseous growth regulation in a very complex but understandable loco-motor system, in which external factors cause muscular reaction that obey all mechanical laws. Lifestyle factors seem to greatly affect deformations

Aims

Significant correction of an adolescent idiopathic scoliosis in the coronal plane through a posterior approach is associated with hypokyphosis. Factors such as the magnitude of the preoperative coronal curve, the use of hooks, number of levels fused, preoperative kyphosis, screw density, and rod type have all been implicated. Maintaining the normal thoracic kyphosis is important as hypokyphosis is associated with proximal junctional failure (PJF) and early onset degeneration of the spine. The aim of this study was to determine if coronal correction per se was the most relevant factor in generating hypokyphosis.

We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements.

Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p <  0.001). Scoliosis developed in virtually all DMD patients not receiving steroids once they became wheelchair-dependent, and the degree of deformity deteriorated over time.

In general, scoliosis increased at a constant rate, beginning at the time of wheelchair-dependency (p < 0.001). In some there was no scoliosis for as long as three years after dependency, but scoliosis then developed and increased at a constant rate. Some patients showed a rapid increase in the rate of progression of the curve after a few years – the clinical phenomenon of a rapidly collapsing curve over a few months.

A sagittal plane kyphotic deformity was seen in 37 of 60 patients (62%) with appropriate radiographs, with 23 (38%) showing lumbar lordosis (16 (27%) abnormal and seven (11%) normal).

This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

Cite this article: Bone Joint J 2014;96-B:100–5.