A Differential Hypofunctionality of Gαi Proteins Occurs in Adolescent Idiopathic Scoliosis and Correlates with the Risk of Disease Progression.

Adolescent idiopathic scoliosis is the most prevalent spine deformity and the molecular mechanisms underlying its pathophysiology remain poorly understood. We have previously found a differential impairment of melatonin receptor signaling in AIS osteoblasts allowing the classification of patients into three biological endophenotypes or functional groups (FG1, FG2 and FG3). Here, we provide evidence that the defect characterizing each endophenotype lies at the level of Gαi proteins leading to a systemic and generalized differential impairment of Gi-coupled receptor signaling. The three Gαi isoforms exhibited a selective serine phosphorylation patterns for each AIS endophenotype resulting in a differential reduction in Gαi protein activity as determined by cellular dielectric spectroscopy and small interfering RNA methods. We found that one endophenotype (FG2) with phosphorylated Gαi1 and Gαi2 was consistently associated with a significantly high risk of spinal deformity progression when compared to the other two endophenotypes (FG1 and FG3). We further demonstrated that each endophenotype is conserved among affected family members. This study expands our understanding of the mechanism underlying the Gi-coupled receptor signaling dysfunction occurring in AIS and provides the first evidence for its hereditary nature. Collectively, our findings offers a new perspective on Gαi hypofunctionality in a human disease by revealing specific serine phosphorylation signatures of Gαi isoforms that may facilitate the identification of AIS patients at risk of spinal deformity progression.

Effect of natural sagittal trunk lean on standing balance in untreated scoliotic girls.

BACKGROUND: Generally, scoliotic girls have a tendency to lean further back than a comparable group of non-scoliotic girls. To date, no study has addressed how standing balance in untreated scoliotic girls is affected by a natural backwardly or forwardly inclined trunk. METHODS: 27 able-bodied young girls and 27 young girls with a right thoracic curve were classified as leaning forward or backward according to the median of their trunk sagittal inclination. Participants stood upright barefoot. Trunk and pelvis orientations were calculated from 8 bony landmarks. Upright standing balance was assessed by 9 parameters calculated from the excursion of the center of pressure and the free moment. FINDINGS: In the anterior-posterior direction, backward scoliotic girls had a greater center of pressure range (P=0.036) and speed (P=0.015) by 10.4mm and 2.8mm/s respectively than the forward scoliotic group. Compared to their matching non-scoliotic group, the backward scoliotic girls stood more on their heels by 14.6mm (P=0.017) and display greater center of pressure speed by 2.5mm/s (P=0.028). Medio-lateral center of pressure range (P=0.018) and speed (P=0.008) were statistically higher by 8.7mm and 3.6mm/s for the backward group. Only the free moment RMS was significantly larger (P=0.045) for the backward scoliotic group when compared to the forwardly inclined scoliotic group. INTERPRETATION: Only those with a backward lean displayed statistically significant differences from both forward scoliotic girls and non-scoliotic girls. Untreated scoliotic girls with an exaggerated back extension could profit more from postural rehabilitation to improve their standing balance.

Head and trunk moments of inertia of able-bodied and unbraced scoliotic girls.

OBJECTIVE: The purposes of this study were to estimate head and trunk's (HT) radii of gyration (K) and moments of inertia (I) in able-bodied and unbraced scoliotic girls using an angular momentum method, to test if the use of mean ratios calculated in this study and given by de Leva present similar values compared to the experimental data, and to determine how these methods behave in estimation of scoliotic HT's K and I with variable Cobb angles. BACKGROUND: Scoliotic HT's I estimated from anthropometric tables can lead to error in joint muscle moment calculations. METHOD: Twenty-one unbraced scoliotic and 20 able-bodied girls participated. HT's I values were calculated using an angular momentum method. RESULTS: Angular momentum method provided greater HT's I for the scoliotic group compared with the able-bodied girls. HT's I obtained by the mean ratios calculated from this study were close to the measured values. Compared with the experimental I, de Leva method provided significantly lower I in the scoliotic group. Scoliotic HT's K and I obtained from angular momentum method showed greater correlations with the Cobb angles. CONCLUSION: The use of mean ratios obtained in this study to estimate HT's K values in unbraced scoliotic girls could overcome the drawbacks of current anthropometric methods. APPLICATION: These results can be used to calculate more precise moments of force during daily activities in scoliotic girls with mild scoliosis and to improve the design of corrective flexible body braces prescribed in cases of rapid interventions in young patients of moderate spinal deformities.

Three-dimensional vertebral wedging and pelvic asymmetries in the early stages of adolescent idiopathic scoliosis.

BACKGROUND CONTEXT: Scoliosis is a three-dimensional (3D) deformation of the spine and the pelvis. Although the relation between the pelvic asymmetries and scoliosis progression was proposed by several authors, it has not been documented over time in adolescent idiopathic scoliosis (AIS). PURPOSE: The objective was to determine whether vertebral wedging and pelvic asymmetries progress in the early stages of AIS before any orthopedic treatment. STUDY DESIGN: The study design included an observational cohort study. PATIENT SAMPLE: Nineteen AIS girls participated in this study. OUTCOME MEASURES: The outcome measures were pelvic and spine geometries from simultaneous biplanar radiographs. METHODS: At the diagnosis, the girls (12.6±1.3 years) had a Cobb angle of 13.9°±6.0°. At the end of their observation period (11 months on average), the scoliosis progressed to 20.5°±5.5°. Bone 3D geometry was reconstructed from biplanar radiographs. Sagittal and frontal wedgings were calculated for five vertebral levels, namely, at the apex and at the two vertebral bodies above and below it. The pelvic geometry was described using five 3D homologous right-left lengths to estimate pelvic asymmetries. Paired t tests were performed on vertebral wedging and pelvic asymmetries to assess their progression between the two evaluations. Principal component (PC) analyses were applied to determine whether vertebral wedging or pelvic asymmetries were predominant at each evaluation. RESULTS: Vertebral wedging was present at the diagnosis (1.76°-5.92°) and generally did not progress until brace prescription. The mean difference between the right and left pelvic normalized lengths was 1.4% and 2.4% for the initial and final evaluations, respectively. Results revealed the width of the right pelvis to be superior by 3%, and this asymmetry progressed to 4.0%. Principal component analysis revealed that initial vertebral wedging was present in seven out of eight parameters of the first three PCs, whereas at the final examination, vertebral wedging and pelvic asymmetries were evenly present. CONCLUSIONS: Our study confirms the presence of vertebral wedging at the early stages of scoliosis. This is the first to document the association between spinal and pelvic deformities over time. Pelvic asymmetries could be responsible for trunk muscle imbalances and lead to reduced neuromuscular control reported in AIS patients. These results could influence body brace fitting.

Three-dimensional vertebral wedging in mild and moderate adolescent idiopathic scoliosis.

BACKGROUND: Vertebral wedging is associated with spinal deformity progression in adolescent idiopathic scoliosis. Reporting frontal and sagittal wedging separately could be misleading since these are projected values of a single three-dimensional deformation of the vertebral body. The objectives of this study were to determine if three-dimensional vertebral body wedging is present in mild scoliosis and if there are a preferential vertebral level, position and plane of deformation with increasing scoliotic severity. METHODOLOGY: Twenty-seven adolescent idiopathic scoliotic girls with mild to moderate Cobb angles (10° to 50°) participated in this study. All subjects had at least one set of bi-planar radiographs taken with the EOS® X-ray imaging system prior to any treatment. Subjects were divided into two groups, separating the mild (under 20°) from the moderate (20° and over) spinal scoliotic deformities. Wedging was calculated in three different geometric planes with respect to the smallest edge of the vertebral body. RESULTS: Factorial analyses of variance revealed a main effect for the scoliosis severity but no main effect of vertebral Levels (apex and each of the three vertebrae above and below it) (F = 1.78, p = 0.101). Main effects of vertebral Positions (apex and above or below it) (F = 4.20, p = 0.015) and wedging Planes (F = 34.36, p<0.001) were also noted. Post-hoc analysis demonstrated a greater wedging in the inferior group of vertebrae (3.6°) than the superior group (2.9°, p = 0.019) and a significantly greater wedging (p≤0.03) along the sagittal plane (4.3°). CONCLUSIONS: Vertebral wedging was present in mild scoliosis and increased as the scoliosis progressed. The greater wedging of the inferior group of vertebrae could be important in estimating the most distal vertebral segment to be restrained by bracing or to be fused in surgery. Largest vertebral body wedging values obtained in the sagittal plane support the claim that scoliosis could be initiated through a hypokyphosis.

Pelvic morphology, body posture and standing balance characteristics of adolescent able-bodied and idiopathic scoliosis girls.

The purpose of this study was to determine how pelvic morphology, body posture, and standing balance variables of scoliotic girls differ from those of able-bodied girls, and to classify neuro-biomechanical variables in terms of a lower number of unobserved variables. Twenty-eight scoliotic and twenty-five non-scoliotic able-bodied girls participated in this study. 3D coordinates of ten anatomic body landmarks were used to describe pelvic morphology and trunk posture using a Flock of Birds system. Standing balance was measured using a force plate to identify the center of pressure (COP), and its anteroposterior (AP) and mediolateral (ML) displacements. A multivariate analysis of variance (MANOVA) was performed to determine differences between the two groups. A factor analysis was used to identify factors that best describe both groups. Statistical differences were identified between the groups for each of the parameter types. While spatial orientation of the pelvis was similar in both groups, five of the eight trunk postural variables of the scoliotic group were significantly different that the able-bodied group. Also, five out of the seven standing balance variables were higher in the scoliotic girls. Approximately 60% of the variation is supported by 4 factors that can be associated with a set of variables; standing balance variables (factor 1), body posture variables (factor 2), and pelvic morphology variables (factors 3 and 4). Pelvic distortion, body posture asymmetry, and standing imbalance are more pronounced in scoliotic girls, when compared to able-bodied girls. These findings may be beneficial when addressing balance and ankle proprioception exercises for the scoliotic population.

Head and trunk mass and center of mass position estimations in able-bodied and scoliotic girls.

Anthropometric tables are not applicable to calculate the scoliotic trunk mass and center of mass (COM). The purposes of this study were: (1) to estimate the head and trunk mass and COM in able-bodied and scoliotic girls using a force plate method, (2) to estimate head and trunk COM offset compared to those of the body, and (3) the use of mean ratios to estimate the head and trunk COM calculated in this study and that calculated according to a conventional three-dimensional (3D) method compared to the measured values. Twenty-one scoliotic and twenty able-bodied girls participated. The subjects stood upright with arms beside the trunk on a force plate that collected data at 60 Hz for a period of 5s. The anteroposterior and mediolateral positions of the body COM were obtained from the mean center of pressure values. The height of the body COM was estimated by the reaction board method. Afterwards a body segment was displaced and changes in force plate readings were recorded and applied to estimate the head and trunk mass and COM. Trunk offset was defined as the difference between the COM of the body and head and trunk. The measured head and trunk COM was compared to values obtained by the mean ratios calculated from this study and given by the conventional 3D method. The relative head and trunk mass and the anteroposterior trunk offset were larger in scoliotic girls. The force plate method gave similar results to measured COM values for both groups underlying its capability to provide a more accurate estimation of COM related values. Thus, the use of mean ratios of 0.5538 and 0.6438 obtained in this study to estimate the head and trunk mass and COM position in scoliotic girls can overcome the main drawbacks of current anthropometric methods, if direct measurements cannot be taken.

Pelvis morphology, trunk posture and standing imbalance and their relations to the Cobb angle in moderate and severe untreated AIS.

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis and usually affects young girls. Studies mostly describe the differences between scoliotic and non-scoliotic girls and focus primarily on a single set of parameters derived from spinal and pelvis morphology, posture or standing imbalance. No study addressed all these three biomechanical aspects simultaneously in pre-braced AIS girls of different scoliosis severity but with similar curve type and their interaction with scoliosis progression. The first objective of this study was to test if there are differences in these parameters between pre-braced AIS girls with a right thoracic scoliosis of moderate (less than 27°) and severe (more than 27°) deformity. The second objective was to identify which of these parameters are related to the Cobb angle progression either individually or in combination of thereof. Forty-five scoliotic girls, randomly selected by an orthopedic surgeon from the hospital scoliosis clinic, participated in this study. Parameters related to pelvis morphology, pelvis orientation, trunk posture and quiet standing balance were measured. Generally moderate pre-brace idiopathic scoliosis patients displayed lower values than the severe group characterized by a Cobb angle greater than 27°. Only pelvis morphology and trunk posture were statistically different between the groups while pelvis orientation and standing imbalance were similar in both groups. Statistically significant Pearson coefficients of correlation between individual parameters and Cobb angle ranged between 0.32 and 0.53. Collectively trunk posture, pelvis morphology and standing balance parameters are correlated with Cobb angle at 0.82. The results suggest that spinal deformity progression is not only a question of trunk morphology distortion by itself but is also related to pelvis asymmetrical bone growth and standing neuromuscular imbalance.

Iliac crest orientation and geometry in able-bodied and non-treated adolescent idiopathic scoliosis girls with moderate and severe spinal deformity.

PURPOSE: To identify pelvic rotation and/or distortion in able-bodied and untreated AIS girls with moderate and severe scoliosis and verify association of pelvic morphological changes with Cobb angle increase. METHODS: The 3D coordinates of nine anatomic bony landmarks were identified to estimate pelvic orientation using a Flock of Birds system. The distances between the first sacral vertebral body (S1) and each of the eight iliac spine landmarks in all three planes were calculated to identify pelvic distortion. Analysis of variance was used to assess pelvic orientation and determine pelvic distortion. Pearson coefficients of correlation were used to identify any relationships between Cobb angle and pelvic morphological parameters. RESULTS: Pelvic orientation was similar in able-bodied and scoliotic girls regardless of the severity of the spinal deformity. Significant differences were observed in pelvic morphology between AIS with severe untreated scoliosis and those with a moderate scoliosis for the right anterosuperior iliac spines (ASIS), the tip of the superior iliac crest (TSIC) and the widest tip of the iliac crest (WTIC) widths from S1. Statistically significant correlations were observed between the Cobb angles and the iliac crest distances measured from S1. CONCLUSIONS: Differences in iliac spine geometries occurred in the transverse plane correlating to Cobb angles which suggest altered bone growth in AIS girls. Such findings could indicate right thoracic spinal deformity as a result of pelvic torsion.

Relationship between oscillations about the vertical axis and center of pressure displacements in single and double leg upright stance.

OBJECTIVES: The purposes of this study are to assess the relationship of the center of pressure (CoP) displacement parameters along the mediolateral and anteroposterior axes to whole-body oscillations about the vertical axis during single or double leg upright stance and to determine whether sensory deprivation and stance modify balance stability about the vertical axis and in the horizontal plane. DESIGN: Eleven male adults stood on a force plate during conditions in which stance (single/double) and/or vision (normal/reduced) were modified independently. The dependent variables were CoP range, CoP velocity, and free moment (TZ) range. R-squared coefficients (R) were applied to assess the relationship between CoP and TZ range, whereas multifactor analysis of variances were used to assess the differences among conditions. RESULTS: R between CoP and TZ parameters varied from 0.16 to 0.69 for three of the four conditions, suggesting that different postural mechanisms controlled CoP displacements and body axial rotations. Single leg stance with reduced vision condition revealed a higher R between CoP velocity and TZ range. TZ range was approximately seven times greater when stance was modified to single limb stance, whereas reduced vision had no effect. CONCLUSIONS: Postural control mechanisms seem to be different for the free moment (TZ) than for the CoP displacements.

Cell-based screening test for idiopathic scoliosis using cellular dielectric spectroscopy.

STUDY DESIGN: A cell-based assay was developed to identify asymptomatic children at risk of developing idiopathic scoliosis (IS) and to stratify IS patients at an earlier stage in order to better predict their clinical outcome. Clinical validation of this assay was performed by testing IS patients at different stages, healthy control subjects, and asymptomatic offspring, born from at least one scoliotic parent, who are considered at risk of developing this disorder. OBJECTIVE: Our goal was to develop and validate a clinical test for IS using cellular dielectric spectroscopy (CDS) and peripheral blood mononuclear cells (PBMCs). SUMMARY OF BACKGROUND DATA: We have previously demonstrated the occurrence of a melatonin signaling dysfunction in osteoblasts obtained from severely affected IS patients using a cAMP assay. This led us to stratify IS patients into 3 functional subgroups. METHODS: A group of 44 patients with IS was compared with 42 healthy control subjects and 31 asymptomatic at-risk children. PBMCs were obtained after centrifugation on a Ficoll-gradient. Melatonin signal transduction was measured by CDS in the presence of varying concentrations of melatonin or iodomelatonin. RESULTS: Osteoblasts from distinct functional subgroups were retested using CDS, allowing their classification into the same functional subgroups with both ligands as initially demonstrated using a cAMP assay. Clinical data obtained with CDS and PBMCs showed 100% specificity and 100% sensitivity because melatonin signaling impairment was observed only in IS patients and not in healthy controls. Assessment of the risk of developing a scoliosis in asymptomatic children was determined by CDS in 33% of asymptomatic children at risk, which was confirmed clinically within 24 months. CONCLUSION: This cell-based assay can serve as a presymptomatic screening test to identify asymptomatic children at risk of developing IS and may be used to improve stratification of patients, which in turn allow clinicians to predict their clinical outcome. Moreover, this functional blood test is advantageous because it can be performed without prior knowledge of specifically mutated genes causing IS.

Influence of orthopedic implant structure on adjacent bone density and on stability.

We evaluated the ability of a porous metallic interbody fusion implant made with porous nitinol (PNT) to achieve intervertebral fusion and the capacity of stabilization at the implantation site 3, 6, and 12 months after implantation. Sixteen sheep each received 1 PNT implant and 1 titanium (TiAIV) cage at intervertebral lumbar levels L2-L3 and L4-L5; 3 other sheep were used as untreated controls. The TiAIV cage was used as a control implant. After animal sacrifice, computed tomography was used to study peri-implant bone mineral density (BMD), and histologic slices were used to evaluate implant osseointegration. BMD around PNT implants was close to physiological (control value) BMD, whereas BMD around TiAIV cages was usually higher (sclerosis) than physiological BMD. Histologic analysis showed better osseointegration with PNT implants than with TiAIV cages. Sclerosis might result from bone acting to stabilize implants in their implantation sites. Compared with PNT implants, TiAIV cages seemed to be unstable in their implantation sites. For PNT implants, osseointegration was successful, and surrounding BMD was close to physiologic BMD.

[Etiopathogenesis of adolescent idiopathic scoliosis and new molecular concepts]. / Récents progrès dans l'étiopathogénie de la scoliose idiopathique de l'adolescent et nouveaux concepts moléculaires.

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis that affects a significant number of young teenagers, mainly females (0.2-6 % of the population). Historically, several hypothesis were postulated to explain the aetiology of AIS, including genetic factors, biochemical factors, mechanics, neurological, muscular factors and hormonal factors. The neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS has generated great interest. This hypothesis stems from the fact that experimental pinealectomy in chicken, and more recently in rats maintained in a bipedal mode, produces a scoliosis. The biological relevance of melatonin in idiopathic scoliosis is controversial since no significant decrease in circulating melatonin level has been observed in a majority of studies. Analysis of melatonin signal transduction in musculoskeletal tissues of AIS patients demonstrated for the first time a defect occurring in a cell autonomous manner in different cell types isolated from AIS patients suffering of the most severe form of that disease. These results have led to a classification of AIS patients in three different functional groups depending on their response to melatonin, suggesting that the cause of AIS involves several genes. Molecular analysis showed that melatonin signaling dysfunction is triggered by an increased phosphorylation of Gi proteins inactivating their function. This discovery has led to development of a first scoliosis screening assay. This test, using blood sample, is currently in clinical validation process in Canada and could be used for screening children at high risk of developing AIS.

Simulation of an anterior spine instrumentation in adolescent idiopathic scoliosis using a flexible multi-body model.

Anterior spinal instrumentation is an alternative option to posterior instrumentation for surgical treatment of adolescent idiopathic scoliosis (AIS). However, optimal instrumentation configuration and strategies are not yet clearly defined. A biomechanical kinematic model using flexible mechanism was developed to study instrumentation strategies. Preoperative 3D reconstruction of scoliotic patient's spine was used to define the patient-specific geometry of the model. Mechanical properties were adjusted to consider the discectomy and surgical manoeuvres were reproduced. Anterior spine surgeries of ten patients were simulated and results were compared to immediate post-operative data and showed differences of <5 degrees for the Cobb angles. The validated model was used to find optimal instrumentation configurations for one patient prior to surgery. Six strategies were tested out of which the optimal one was identified while two were not recommended for surgery since screw forces exceeded published pullout forces. This study demonstrates the possibility to simulate anterior spine instrumentations.

Free moment contribution to quiet standing in able-bodied and scoliotic girls.

Adolescent idiopathic scoliosis girls are known to display standing imbalance. In addition to a motor deficit problem, the axial torsion of the spine and trunk torsion could reflect an imbalance around the vertical axis. Unlike the excursion of the center of pressure (COP), the forces and moments were rarely addressed to characterize the quiet standing balance. Nonetheless, one dynamical parameter, called free moment (T(V)), representing the vertical torque on the feet can reflect the oscillation around the vertical axis associated to the standing imbalance. The objectives of this study were to test if the free moment variability can be utilized to characterize standing balance in a group of able-bodied and non-treated scoliotic girls and to determine if it was associated with that of the COP among each group of subjects tested. Forty-six adolescent girls with half of them presenting an adolescent idiopathic scoliosis were tested during quiet standing balance. Standing balance was assessed with the subjects standing upright and bare feet on a force plate. RMS and range of COP excursions and free moment were calculated. The scoliotic group displayed higher variability in COP excursion by about 24% than the able-bodied girls. Similarly, the T(V) RMS (P = 0.00136) and range (P = 0.00197) were statistically higher by about 42% in the scoliotic group. The variability of T(V) was associated with that of the COP in both groups. In the medio-lateral direction, the significant correlations between the RMS and range of the free moment and those of the COP were about 0.7 for the able-bodied group and 0.5 for the medio-lateral COP range for the scoliotic group girls. Along the antero-posterior axis, the only statistically significant correlations were observed for the scoliotic group. The free moment variability about the COP measured during quiet standing can be suggestive of an asymmetry control of the trunk around the vertical axis during standing balance. Its variability was more pronounced in scoliotic girls and was associated with the antero-posterior COP variability reflecting both biomechanical and motor control deficits. Free moment calculation could be a supplement insight into the standing balance of scoliotic subjects.

Assessment of the paraspinal muscles of subjects presenting an idiopathic scoliosis: an EMG pilot study.

BACKGROUND: It is known that the back muscles of scoliotic subjects present abnormalities in their fiber type composition. Some researchers have hypothesized that abnormal fiber composition can lead to paraspinal muscle dysfunction such as poor neuromuscular efficiency and muscle fatigue. EMG parameters were used to evaluate these impairments. The purpose of the present study was to examine the clinical potential of different EMG parameters such as amplitude (RMS) and median frequency (MF) of the power spectrum in order to assess the back muscles of patients presenting idiopathic scoliosis in terms of their neuromuscular efficiency and their muscular fatigue. METHODS: L5/S1 moments during isometric efforts in extension were measured in six subjects with idiopathic scoliosis and ten healthy controls. The subjects performed three 7 s ramp contractions ranging from 0 to 100% maximum voluntary contraction (MVC) and one 30 s sustained contraction at 75% MVC. Surface EMG activity was recorded bilaterally from the paraspinal muscles at L5, L3, L1 and T10. The slope of the EMG RMS/force (neuromuscular efficiency) and MF/force (muscle composition) relationships were computed during the ramp contractions while the slope of the EMG RMS/time and MF/time relationships (muscle fatigue) were computed during the sustained contraction. Comparisons were performed between the two groups and between the left and right sides for the EMG parameters. RESULTS: No significant group or side differences between the slopes of the different measures used were found at the level of the apex (around T10) of the major curve of the spine. However, a significant side difference was seen at a lower level (L3, p = 0.01) for the MF/time parameter. CONCLUSION: The EMG parameters used in this study could not discriminate between the back muscles of scoliotic subjects and those of control subject regarding fiber type composition, neuromuscular efficiency and muscle fatigue at the level of the apex. The results of this pilot study indicate that compensatory strategies are potentially seen at lower level of the spine with these EMG parameters.

Melatonin signaling dysfunction in adolescent idiopathic scoliosis.

STUDY DESIGN: In vitro assays were performed with bone-forming cells isolated from 41 patients with adolescent idiopathic scoliosis and 17 control patients exhibiting another type of scoliosis or none. OBJECTIVE: To determine whether a dysfunction of the melatonin-signaling pathway in tissues targeted by this hormone is involved in adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomy in chicken has led to the formation of a scoliotic deformity, thereby suggesting that a melatonin deficiency may be at the source of adolescent idiopathic scoliosis. However, the relevance of melatonin in the etiopathogenesis of that condition is controversial because most studies have reported no significant change in circulating levels of melatonin in patients with adolescent idiopathic scoliosis. METHODS: Primary osteoblast cultures prepared from bone specimens obtained intraoperatively during spine surgeries were used to test the ability of melatonin and Gpp(NH)p, a GTP analogue, to block cAMP accumulation induced by forskolin. In parallel, melatonin receptor and Gi protein functions were evaluated by immunohistochemistry and by coimmunoprecipitation experiments. RESULTS: The cAMP assays demonstrated that melatonin signaling was impaired in osteoblasts isolated from adolescent idiopathic scoliosis patients to different degrees allowing their classification in 3 distinct groups based on their responsiveness to melatonin or Gpp(NH)p. CONCLUSION: Melatonin signaling is clearly impaired in osteoblasts of all patients with adolescent idiopathic scoliosis tested. Classification of patients with adolescent idiopathic scoliosis in 3 groups based on functional in vitro assays suggests the presence of distinct mutations interfering with the melatonin signal transduction. Posttranslational modifications affecting Gi protein function, such as serine residues phosphorylation, should be considered as one possible mechanism in the etiopathogenesis of AIS.

The effect of intraoperative traction during posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective study comparing patients having traction and a control group not having traction during posterior spinal instrumentation and fusion (PSIF) for adolescent idiopathic scoliosis (AIS). OBJECTIVE: To evaluate the effect of intraoperative traction on surgical correction of AIS. SUMMARY OF BACKGROUND DATA: When the Cotrel-Dubousset instrumentation system was introduced, the use of intraoperative traction was advocated. However, there is no specific report documenting the effect of intraoperative traction on the correction of AIS. METHODS: The medical and radiologic records of 140 AIS patients treated by PSIF were reviewed. Forty of these patients had intraoperative traction using a head halter associated with lower extremity skin traction. The radiologic outcome was compared between the two groups intraoperatively (before instrumentation with the first rod) and after surgery using Student t tests (level of significance = 0.05). RESULTS: The intraoperative and postoperative corrections of the coronal primary Cobb angle were similar for both groups, although the patients in the traction group had smaller preoperative Cobb angles and more flexible curves and were instrumented with more screws. The postoperative thoracic kyphosis was significantly increased in both groups. The lumbar lordosis at the 1-year follow-up was maintained in the control group, but it was significantly decreased in the traction group. CONCLUSION: The authors do not recommend the routine use of intraoperative traction using a head halter combined with skin traction for all AIS patients undergoing PSIF. However, it could be helpful in selected cases, such as in patients having pelvic obliquity and requiring instrumentation of the pelvis.

SpineCor--a non-rigid brace for the treatment of idiopathic scoliosis: post-treatment results.

The objective of this study was to assess the success of treatment during the follow-up of a group of 195 idiopathic scoliosis (IS) patients consecutively treated with the SpineCor system. A survival analysis was performed to estimate the cumulative probability of success during treatment, at follow-up and for the combined treatment and follow-up period. Success was defined as either a correction or stabilization of +/-5 degrees or more, and failure as a worsening of more than 5 degrees. The patient cohort was categorized before treatment into curves less than 30 degrees (group 1), and curves greater than 30 degrees (group 2). The survival analysis indicated a cumulative probability of success that increased during treatment with the patient wearing the brace (Year 1: 0.30, 0.39; Year 2: 0.62, 0.79; Year 3: 0.92, 0.89, for groups 1 and 2 respectively). During the post-treatment follow-up period, there was a stabilization (Year 1 post-treatment: 0.94, 0.89; Year 2 post-treatment: 0.85, 0.81), with an overall probability of success of 0.92 and 0.88 after 4 years of combined treatment and post-treatment follow-up. For the 29 patients who had a minimum follow-up of 2 years (initial Cobb angle: 30 degrees +/-9 degrees ), the trend during treatment was a decrease in spinal curvature at 3 months, with a mean difference of 10 degrees (SD 5 degrees ); at termination of treatment a mean difference of 7 degrees (SD 7 degrees ); and at the time of the 1- and 2-year follow-ups there was a difference of 4 degrees (SD 7 degrees ) and 5 degrees (SD 7 degrees ) respectively, with reference to the initial out of brace condition. At 2 years follow-up there was an overall correction of greater than 5 degrees for 55% of the patients, 38% had a stabilisation and 7% had worsened by more than 5 degrees. This initial cohort of patients demonstrated a general trend of initial decrease in spinal curvature in brace, followed by a correction and/or stabilisation at the end of treatment, which was maintained through 1, and 2 years' follow-up.