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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 55 - 55
1 Dec 2022
Duarte MP Joncas J Parent S Labelle H Barchi S Mac-Thiong J
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To compare preoperative and postoperative Health Related Quality of Life (HRQoL) scores in operated Adolescent Idiopathic Scoliosis (AIS) patients with and without concomitant isthmic spondylolisthesis.

A retrospective study of a prospective cohort of 464 individuals undergoing AIS surgery between 2008 and 2018 was performed. All patients undergoing surgery for AIS with a minimum 2-year follow-up were included. We excluded patients with prior or concomitant surgery for spondylolisthesis. HRQoL scores were measured using the SRS-22 questionnaire. Comparisons were performed between AIS patients with vs. without concomitant spondylolisthesis treated non-surgically.

AIS surgery was performed for 36 patients (15.2 ±2.5 y.o) with concomitant isthmic spondylolisthesis, and 428 patients (15.5 ±2.4 y.o) without concomitant spondylolisthesis. The two groups were similar in terms of age, sex, preoperative and postoperative Cobb angles. Preoperative and postoperative HRQoL scores were similar between the two groups. HRQoL improved significantly for all domains in both groups, except for pain in patients with spondylolisthesis. There was no need for surgical treatment of the spondylolisthesis and no slip progression during the follow-up duration after AIS surgery.

Patients undergoing surgical treatment of AIS with non-surgical management of a concomitant isthmic spondylolisthesis can expect improvement in HRQoL scores, similar to that observed in patients without concomitant spondylolisthesis.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 54 - 54
1 Dec 2022
Pereira Duarte M Joncas J Parent S Duval M Chemaly O Brassard F Mac-Thiong J Barchi S Labelle H
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There is a significant positive association between hours of brace wear and rate of success in the treatment of Adolescent Idiopathic Scoliosis (AIS). The abandon rate reported in the literature averages 18%. In a recent randomized trial conducted at our center; the abandon rate was 4%. We aim to document the abandon rate towards brace treatment during the COVID-19 pandemic and its impact on AIS progression.

We reviewed a database of AIS patients recruited between March and September 2020. Inclusion criteria were patients with AIS under brace treatment according to SRS criteria. The patients were divided in 2 cohorts: those with a self-reported good adherence to treatment and those who voluntarily abandoned treatment during follow-up. Patients with irregular adherence were excluded. Data analysis included age, gender, Risser stage, type of brace, Cobb angles at first visit and last follow-up (mean 11 months) and % of progression. Unpaired student tests were used for comparison.

154 patients met inclusion criteria. 20 patients were excluded due to irregular adherence. 89 patients (age: 12.1 y.o. ±1.4) reported good adherence to treatment, while 45 patients (age: 12.6 y.o. ±1.5) abandoned treatment, an abandon rate of 29%. The cohort of compliant patients started treatment with a mean main thoracic (MT) curve of 26° and finished with 27°. The mean difference between measurements was +0.65°±7.5; mean progression rate was −4.6%. However, patients who abandoned treatment started with a mean MT curve of 28° and finished with 33°, with a mean increase of +5°±8 and a mean progression rate of −11%. The differences between the 2 cohorts were statistically significant (p=0.002). Five (5) patients from the abandon group were offered for surgery because of curve progression.

The abandon rate of brace treatment in AIS significantly increased during the first wave of COVID-19 pandemic. Patients who voluntarily discontinued treatment had significant increases in curve progression and surgical indication rates.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 69 - 69
1 Nov 2016
Beausejour M Brousselle A Breton M Eshiemokhai M Saran N Labelle H Parent S Mac-Thiong J Ouellet J
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Referral patterns in spine clinic of young patients with suspected scoliosis is suboptimal with 19% of late referrals and 42% of inappropriate referrals. Patients' triage and prioritisation in spine clinic is a strategy to ensure that health care allocation is done according to the level of health needs, favoring effective management and efficient use of health care resources use. The objective of the study is to elaborate a model for triage and prioritisation of young patients in spine clinic based on expert consensus and literature on best practices.

This projects was structured in three parts: 1)We documented best evidence. We conducted a review of empirical studies evaluating triage and prioritisation initiatives in order to identify key components for intervention success. 2)We elaborate a model of health care delivery with the professionals of a local paediatric spine clinic. In this model, the triage and prioritisation algorithm was developed from list of potential factors (demographics, signs and perceived symptoms, provisional diagnoses and known co-morbidities, results of preliminary physical examination and radiological findings) that was submitted to five paediatric orthopaedic surgeons for rating according to their potential relevance to orient prioritisation decisions. 3) We compared the professionals' model of health care delivery to the literature synthesis in order to propose the best model.

Seven key components of triage and prioritisation systems were identified: centralised review of referral requests, list of consensual objectives criteria for triage, fast track evaluation of urgent cases, selection of cases for management at point of triage, cases prioritisation to main consultant, multidisciplinary evaluation and alternatives pathways. The consensual decision algorithm confirmed that cases who should be seen in priority are immature patients presenting with a significant trunk deformity. In addition, presence of persisting neurological symptoms, severe incapacitating pain or night pain, as well as abnormal scan or MRI findings were considered as urgent/PI priority. Cases characteristics for evaluation by nurse practitioners as well as alternative pathways of management were defined. Acceptability, compatibility, clinical relevance and discriminant capacity of the new model of health care delivery were satisfactorily demonstrated.

Consensus was easily reached between the five respondents on factors supporting decisions to prioritise patients in spine clinic for suspected spinal deformity. Refinements to the initially proposed model according the identified key features from the literature, led to a final model of health care delivery that is evidence-base, feasible and coherent with the local context. Future implementation of this model should facilitate timely and appropriate health care delivery and best use of health care resources according to patients' needs.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 48 - 48
1 Jun 2012
Moreau A Yuan Q Akoume M Karam N Taheri M Bouhanik S Rompre P Bagnall K Labelle H Poitras B Rivard C Grimard G Parent S
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Introduction

From the many human studies that attempt to identify genes for adolescent idiopathic scoliosis (AIS), the view emerging is that AIS is a complex genetic disorder with many predisposing genes exhibiting complex phenotypes through environmental interactions. Although advancements in genomic technology are transforming how we undertake genetic and genomic studies, only some success has been reached in deciphering complex diseases such as AIS. Moreover, the present challenge in AIS research is to understand the causative and correlative effects of discovered genetic perturbations. An important limitation to such investigations has been the absence of a method that can easily stratify patients with AIS.

To overcome these challenges, we have developed a functional test that allows us to stratify patients with AIS into three functional subgroups, representing specific endophenotypes. Interestingly, in families with multiple cases of AIS, a specific endophenotype is shared among the affected family members, indicating that such a transmission is inherited. Moreover, increased vulnerability to AIS could be attributable to sustained exposure to osteopontin (OPN), a multifunctional cytokine that appears to be at the origin of the Gi-coupled receptor signalling dysfunction discovered in AIS. We examined the molecular expression profiles of patients with AIS and their response to OPN.

Methods

Osteoblasts isolated from patients with AIS were selected for each functional subgroup and compared with osteoblasts obtained from healthy matched controls. We used the latest gene chip human genome array Affymetrix (HuU133 Plus 2.0 array) that allows for the analysis of the expression level of 38 000 well characterised human genes. Raw data were normalised with robust multiarray analysis method. Statistical analysis was done by the EB method with FlexArray software. Selection criteria for in-depth analysis include the magnitude of change in expression (at least □} 3-fold) and 5% false discovery rate as stringency selection. Validation of selected candidate genes was done by qPCR and at the protein level by Western blot and ELISA methods. Plasma OPN concentrations were measured by ELISA on a group of 683 consecutive patients with AIS and were compared with 262 healthy controls and 178 asymptomatic offspring, born from at least one scoliotic parent, and thus considered at risk of developing the disorder. The regulation of OPN signalling pathway in normal and AIS cells were validated in vitro by cellular dielectric spectroscopy (CDS).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 42 - 42
1 Jun 2012
Fendri K Patten S Zaouter C Parent S Labelle H Edery P Moldovan F
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Introduction

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity. It occurs mainly in girls and progresses during pre-pubertal and pubertal growth, which is a crucial period for bone mass acquisition. The cause and molecular mechanisms of AIS are not clear; at present the consensus is that AIS has a multifactor cause, with many genetic factors. During the past 5 years, considerable effort has been devoted to identify a gene or genes that cause a predisposition to AIS. Many loci for this disorder have been mapped to different chromosome regions, but no genes have been clearly identified as being responsible for AIS, and, most importantly, the resulting protein defects remain to be shown. We aimed to identify the gene(s) that could be involved in AIS and to validate their involvement by both genetic and functional analyses.

Methods

A large multiplex AIS French family was chosen for this study on the basis of clinical and radiological data. Whole genome genotyping of the 20 members of this family led to the mapping of a dominant disease-causing gene to two critical genomic intervals (Edery and colleagues, Eur J Hum Genet, accepted [2011]), but the causative mutation remains to be identified. In parallel, gene expression profiling was investigated by microarray analysis in RNA samples isolated from osteoblasts derived from healthy individuals and those with AIS. RNA samples were extracted from osteoblasts, purified, fluorescently labelled, and then hybridised to gene expression microarrays with the Illumina expression BeadChips technology containing more than 46 000 probes for the human genome (HumanHT-12). Data analysis in R version 2.10.1 (Bioconductor packages oligo and limma) was done, and genes that had at least 1·5-fold change in expression were considered differentially regulated relative to controls. AIS candidate genes within the critical intervals were selected on the basis of their mRNA expression in AIS individuals and by their known functions. The coding regions of these candidate genes were then sequenced to identify potential mutations. The biological activity of mutant proteins is under evaluation by in-vivo functional studies in zebrafish.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 593 - 593
1 Nov 2011
Nault M Parent S Roy-Beaudry M de Guise JA Labelle H
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Purpose: Prediction of progression is actually impossible in adolescent idiopathic scoliosis (AIS). Potential risk factor to consider at first visit might be morphologic parameters of the spine. The objective of this study was to compare 3D morphologic parameters of the spine in a non evolutive an in an evolutive group of AIS.

Method: A retrospective cohort study was done. Two groups were recruited with sample size based on a difference of 5 degrees for rotation parameters. First group were all surgical patients (n=19) and second group non evolutive patient (n=18). Inclusion criteria were

Risser sign of 0 or 1

Cobb angle between 11 and 40 degrees

AP and lateral radiograph available.

Exclusion criteria were

limb length discrepancy

syndromic or congenital scoliosis.

All spines were reconstructed in 3D with AP and lateral radiographs of the first visit and measurements were performed on the reconstruction. There were 4 categories of measurements done: Cobb angle, wedging, rotation, slenderness. Student t test were performed.

Results: There was no statistical difference between the two groups for Cobb angle in maximal plane, for lordosis and kyphosis. Differences were found for wedging of the apical disk in 3D plane (S=5,4° vs NE= 0,7° with p=0,04). For coronal orientation of the apex (S=7,8° vs NE=0,1° with p=0,01). For axial orientation of inferior junctional vertebrae (S=1,9° vs 0,1° with p=0,007). For torsion (S=−4,1° vs NE= – 1,2° with p=0,03). For ratio between height and width of T6 (S=51% vs NE=53,6% with p=0,04).

Conclusion: This study give for the first time some 3D morphologic parameters that could be use in the prediction of AIS. Some limitations exist such as the small sample size and the low level of significance. In the future those parameters will be used in the development of a prediction model base on those keys parameters that will confirm the actual findings.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 500 - 501
1 Nov 2011
Parent S Deschênes S Charron G Beaudoin G Labelle H Miron M Dubois J
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Purpose of the study: Recent studies have shown that the incidence of certain cancers would be due to ionising radiation received during diagnostic radiological explorations. It is thus important to optimise dosimetry. In this context, slot scanners have demonstrated potential for generating images with a quality comparable with conventional systems but with a considerable reduction in dose. We wanted to verify this proposition.

Material and method: Radiographs were obtained in 50 scoliosis patients (posteroanterior and lateral incidences) using the slot scanner (EOS, Biospace) and with a conventional machine (FCR-7501S, Fuji). A dosimeter was placed on the patient after each exam. Phantoms were used to adjust radiographic parameters for each system in order to obtain comparable quality images. Patient images were then acquired ad the dose calculated at several entry points. These measures were used to compare skin radiation and to initialise a Monte-Carlo simulation calculating the effective dose. Two orthopaedic surgeons and two radiologists then evaluated the visibility of the structures of interest using a standard check list. They read the images in random order and were blinded to all information concerning the patient and the system used to acquire the images. Visibility was noted on a non-parametric scale with 4 levels. Wilcoxon’s test was used to compare the visibility scores.

Results: Mean radiation of the skin in the thoracoab-dominal region varied from 0.11 to 0.30 mGy (effective dose 0.057 mSv) for the EOS and 0.73 to 2.47 mGy (effective dose 0.460 mSv) for the FCR-7501S. EOS provided significantly superior visibility for all structures (frontal view, p< 0.006), lateral view p< 0.04) except for the posterior arch of the lumbar vertebrae in the lateral view for which visibility was superior for FCR-7501S (p< 0.003).

Discussion: Using the slot scanner, the patients received 6 to 9 times less radiation to the skin for the thoracoab-dominal region and an 8-fold reduction in effective dose than with the conventional system. In addition, the doses presented in the literature for the same exam are much higher than reported for EOS.

Conclusion: The EOS slot scanner offers image quality which is globally superior to conventional systems while considerably reducing radiation dose.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 284 - 284
1 Jul 2011
Nault M Parent S Roy-Beaudry M Rivard M Labelle H
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Purpose: In pediatric orthopedics, Risser sign is used to assess skeletal maturity. Two grading system exist for the Risser sign, one US and one European. In adolescent idiopathic scoliosis (AIS) the curve acceleration phase begin at a digital skeletal age (DSA) score between 400 – 425. The objective was to asses the disagreement between both grading system and evaluate the best estimator of the curve acceleration phase.

Method: One hundred twenty-one AIS patients had a PA and lateral X-rays of the spine and a left hand and wrist X-ray. Risser sign was measured according to both grading system and bone age was calculated according to Tanner-Whitehouse III method. Kappa statistics were done to evaluate concordance between US and Euro-pean grading system and 2 multiple linear regression models were performed to find which stage best predicts the beginning of the rapid acceleration phase.

Results: Kappa statistic between the US and European system was 0.517 (moderate agreement). US Risser 1 was the best predictor of the curve acceleration phase. DSA scores predicted with Risser 1 were 425 and 445 for US and European system respectively.

Conclusion: American and European Risser grading system use different criteria to define 6 stages of a same sign. This is reflected in our study with a moderate agreement between both grading systems. US Risser 1 is the stage that best predicts the beginning of the rapid acceleration phase and a close follow up should be made at the beginning of the iliac apophysis ossification.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 10 - 10
1 Mar 2010
Glavas PP Mac-Thiong J Parent S de Guise JA Labelle H
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Purpose: To determine the reliability of six measurement techniques for lumbosacral kyphosis.

Method: Using custom computer software, four raters evaluated 60 standing lateral radiographs of the lumbosacral spine during two sessions at a one week interval. The sample size consisted of 20 normal, 20 low and 20 high grade spondylolisthetic subjects. Six parameters were included for analysis: Boxall’s slip angle; Dubousset’s lumbosacral angle (LSA); the Spinal Deformity Study Group’s (SDSG) LSA; dysplastic SDSG LSA; sagittal rotation (SR); kyphotic Cobb angle (k-Cobb). Intra- and inter- rater reliability for all parameters was assessed using intra-class correlation coefficients (ICC). Correlations between parameters and slip percentage were evaluated with Pearson coefficients.

Results: The intra-rater ICC’s for all the parameters ranged between 0.81 and 0.97 and the inter-rater ICC’s were between 0.74 and 0.98. All parameters except sagittal rotation showed a medium to large correlation with slip percentage. Dubousset’s LSA and the kyphotic Cobb angle showed the largest correlations (r=−0.78 and r=−0.50, respectively). Sagittal rotation was associated with the weakest correlation (r=−0.10). All other parameters had medium correlations with percent slip (r=0.31 to 0.43).

Conclusion: All measurement techniques provided substantial to almost perfect inter- and intra- rater reliability. Dubousset’s LSA showed the strongest correlation with slip grade. However, this parameter does not reflect the local dysplastic changes that occur in lower L5 and upper S1 endplates. A longitudinal study evaluating the best suited parameter for predicting the risk of progression and response to surgical treatment is warranted.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 28 - 28
1 Mar 2010
Parent S Wang Z Mac-Thiong J Petit Y Labelle H
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Purpose: To determine the relationship between sacral morphology and developmental L5/S1 spondylolisthesis in children and adolescent.

Method: A radiographic study was conducted to investigate sacral morphology in developmental L5/S1 spondylolisthesis in a pediatric and adolescent population. The lateral standing radiographs of 131 subjects, aged 6 to 20 years old with developmental L5-S1 spondylolisthesis (91 low grade and 40 high grade) were analyzed with a dedicated software allowing to measure the following parameters, which were analyzed for each subject by the same individual and compared to an age and sex-matched cohort of 120 asymptomatic subjects: the sacral table index (STI), the sacral table angle (STA), the sacral kyphosis (SK), S1 superior angle, S2 inferior angle, and grade of spondylolisthesis. Student t tests were used to compare the parameters between the curve types.

Results: This study demonstrated that STA is significantly smaller (p< 0.01) in children and adolescents with L5-S1 spondylolisthesis compared to a similar control group. Furthermore, STA is significantly smaller in high grade spondylolisthesis when compared to subjects with low grade. There is also a significant difference in segmental sacral morphology (S1 and S2 anatomy) in the spondylolisthesis group. Increasing sacral kyphosis is also found to be significantly associated with spondylolisthesis.

Conclusion: The sagittal sacral morphology is a constant anatomic variable specific to each normal individual. The anatomy of the sacrum in children and aldolescentss with L5-S1 spondylolisthesis is particular and different from a control group. This study suggests that sacral anatomy may have a direct influence on the development of spondylolisthesis: a lower STA and higher sacral kyphosis may be two factors predisposing to vertebral slip in developmental spondylolisthesis.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 431 - 431
1 Aug 2008
Moldovan F Letellier K Azeddine F Lacroix G Wang D Turgeon I Grimard G Labelle H Moreau A
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Introduction: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, which appears to be caused by a melatonin signalling dysfunction proved recently in osteoblasts. This pathology occurs and progresses during the time of pre-puberty and puberty growth. This period is known to be under the hormonal control and coincides with many biological changes related to the secretion of estrogens, of which estradiol (E2) is the most active. The female prevalence of AIS disease is clearly evident. Indeed, in Quebec the spine deformities considered clinically significant (at least 11° of deformity) are found in a girl:boy ratio of approximately 2:1 for reduced scoliosis, and this ratio increases to 10:1 for scoliosis of more than 30o of deformation. However, the reason for this female prevalence as well as the role of estrogens and estrogen receptors in AIS is not clear despite the fact that these hormones are known for their impact on bone and bone growth, including the spine.

The purpose of the present study was to investigate the role of E2 on the responsiveness of the AIS cells to the melatonin, to determine the expression of estrogens receptors (ERα and ERβ) in AIS tissues and to clarify the impact of estrogen receptor gene polymorphisms in the pathogenesis of AIS.

Methodology: The effects of oestrogen on the AIS osteoblasts (n=10) response to the melatonin was determined by measuring the reduction of forskolin-induced cAMP accumulation. The forskolin treated osteoblasts were incubated in the presence of increasing amounts of melatonin (10–11 to 10-5 M) with or without physiological concentrations (10-10 M) of 17-β-estradiol for 16 hours, and the intracellular cAMP measured by radio-immunoassay using Biotrak Kit. Using RT-PCR, we determined ERα and ERβ mRNA expression in osteoblasts from AIS patients (n=14). Polymorphisms of the first intron of the ERα gene, which contains the XbaI and PvuII polymorphisms, were investigated by PCR following digestion with restriction enzyme and using the genomic DNA from lymphocytes isolated from scoliotic patients (n=33). Using the restriction enzymes XbaI and PvuII, the allelic variants XX, Xx, xx, PP, Pp, and pp were identified in 33 AIS patients (uppercase letters represent absence, and lowercase letters represent presence of restriction sites).

Results: The intracellular level of cAMP was significantly increased (p< 0.01) in the presence of a physiological concentration of 17-β-estradiol (10-10 M) when compared to the level observed in the presence of melatonin alone (10-9 M) (melatonin + estradiol: 109.46 ± 20.07; melatonin 76.09 ± 12.32 (mean ± SD)). As previously described by Dr Moreau’s team, the same pattern (three type of response to melatonin) takes place in the presence of 17-β-estradiol. We observed the loss of ERβ gene expression in 8/ 14 AIS patients contrasting with ERα gene expression that was found in all AIS patients. The XbaI and PvuII polymorphisms were found in 70% (23/33) and 80% (26/33) of the cases respectively. Of the 33 cases, 21 presented both digestion sites, 24 presented PvuII digestion site (6 homozygote, 18 heterozygote) and 23 (8 homozygote, 15 heterozygote) presented XbaI digestion site. The allelic variants were found as follows: XX: n=8, Xx: n=15, xx: n=8, PP: n=6, Pp: n=18 and pp: n=6. Classified by their location in the spine, seven right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and nine right thoracic-left lumbar were found among the patients presenting PvuII positive polymorphism. Among the patients with XbaI positive polymorphism, six right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and eight right thoracic left lumbar were found.

Conclusion: These results show the antagonistic effects of the 17-β-estradiol on AIS osteoblasts response to the melatonin. Thus estrogens interference with melatonin signalling activity would act as a triggering or aggravating factor in the pathogenesis of AIS. At the molecular level, it is possible that estrogens attenuate the response of AIS cells to melatonin through the desensitization of melatonin receptors. The loss of ERβ expression in a significant number of AIS patients appears to be important for the change of the ERα/ERβ receptors ratio that consequently may perhaps alter estrogens signalling pathways. The XbaI and PvuII polymorphisms are present in a significant number of AIS patients but this was not dependant of the curve pattern. These results clearly support the interplays and crosstalk between estrogens and melatonin signalling pathways in AIS aetiopathogenesis.

Supported by the Fondation Yves Cotrel, Institut de France


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 442 - 442
1 Aug 2008
Moreau A Azeddine B Labelle H Poitras B Rivard C Ouellet J Grimard G
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Introduction: Spinal deformities and scoliosis in particular, represent the most prevalent type of orthopaedic deformities in children and adolescents. At present, the most significant problem for clinicians is that there is no proven method or test available to identify children or adolescents at risk of developing AIS or to identify which of the affected individuals are at risk of progression. As a consequence, the application of current treatments, such as bracing or surgical correction, has to be delayed until a significant deformity is detected or until a significant progression is clearly demonstrated, resulting in a delayed and less optimal treatment. Among patients with AIS needing treatment, 80% to 90% will be treated by brace and 10% will need surgery to correct the deformity by spinal instrumentation and fusion of the thoracic and/or lumbar spine. About 15000 such surgeries are done every year in North America, resulting in significant psychological and physical morbidity. Moreover, there is no pharmacotherapy available to either prevent or reduce spinal deformities due mainly to our limited knowledge of AIS aetiopathogenesis. We have recently reconciled the role of melatonin in AIS aetiopathogenesis by demonstrating a melatonin signalling dysfunction occurring in a cell autonomous manner in cells derived from AIS patients exhibiting severe scoliotic deformities. This defect could potentially explain the majority of abnormalities reported in AIS since melatonin receptors and signalling activities are normally found in all tissues and systems affected in AIS, thus offering a very innovative and unifying concept to explain the aetiology of AIS. Moreover, several lines of evidence suggested that inactivation of Gi proteins by an increased phosphorylation of serine residues could be at the source of this signalling defect in AIS. The goals of that study were to assess the possibility to establish a molecular classification of AIS patients and to demonstrate the feasibility to correct this melatonin signalling defect in cells of AIS patients using therapeutic compounds.

Methods: Primary cell cultures were prepared from musculoskeletal tissues of AIS patients (n=150) and age- and gender-matched controls (n=35) obtained intra-operatively. An informed consent was obtained for each subject as approved by our Institutional Ethical Committee. The osteoblasts, the bone-forming cells, were selected to assess whether or not an alteration of melatonin signalling pathway occurs in AIS and accordingly to identify which component of the melatonin transduction machinery could be involved. Co-immunoprecipitation experiments with membrane extracts were performed to identify interacting molecules with key components of melatonin signal transduction machinery. The functionality of melatonin signalling was assessed by investigating the ability of Gi proteins to inhibit stimulated adenyl cyclase activity in osteoblast cultures. Inhibition curves of cAMP production were generated by adding melatonin to the forskolin-containing samples in concentrations ranging from 10-11M to 10-5M in a final volume of 1 ml of _-MEM media containing 0.2% bovine serum albumin (BSA) alone or in presence of 2.5 _M of therapeutic compound A or therapeutic compound B (the nature of both compounds tested cannot be disclosed at this stage). The cAMP content was determined using an enzyme immunoassay kit (Amersham-Pharmacia Biosciences). All assays were performed in duplicate. A non-parametric test, the Wilcoxon matched pairs test was performed to verify the significance between 2 means. Significance was defined as P< 0.05.

Results: Osteoblasts from patients with AIS showed a lack or a markedly reduced inhibition of forskolin-stimulated adenyl cyclase activity by melatonin generating three distinct response-curves corresponding to three functional groups. In order to identify candidate genes involved in AIS aetiopathogenesis, we focused our attention on known kinases and phosphatases modulating Gi protein functions and characterised their interacting partners. Interestingly, PKC_ was initially targeted owing to its property to phosphorylate Gi proteins in vitro. Indeed, in normal osteoblast interactions occurring between MT2 melatonin receptor and RACK1 (a cytosolic protein that bind to and stabilises the actives form of PKC and permits its translocation to different sites within the cells) and PKC_ were detected although those interactions among different AIS patients were altered. Interestingly, treatment with compound A or B rescued melatonin signal defect in cells derived from 36% and 47% of AIS patients respectively. Overall, melatonin signal transduction was restored in cells of 64% of AIS patients (23/36) when treated by one of these therapeutic compounds.

Conclusions: The functional classification of AIS patients is correlated at the molecular level by distinct interactions between key molecules normally involved in melatonin signal transduction in spite that these patients exhibited the same curve type (right thoracic, Lenke type 1). Collectively, these data strongly argue that traditional curve pattern classification is not a relevant stratification of AIS patients to identify its genetic causes. Moreover, using that molecular system we have demonstrated also the possibility to identify therapeutic compounds to rescue the melatonin signalling defect observed in AIS without any prior knowledge of mutations in any defective genes causing AIS because we are measuring a function.

Research project supported by La Fondation Yves Cotrel de l’Institut de France


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 118 - 118
1 Mar 2008
Labelle H Roussouly P Gollogly S Berthonnaud E Labelle H Weidenbaum M
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This study using digitized radiographs and custom software demonstrates that patients with spondylolysis and low-grade spondylolisthesis have increased Pelvic and L5 Incidence as well as a more vertically oriented L5-S1 intervertebral disc than patients without radiographic abnormality of the spine. We propose that shear across the more vertical L5-S1 disc may underlie the etiology of spondylolysis when Pelvic Incidence is high, while a “nutcracker” mechanism may be involved when Pelvic Incidence is low.

The purpose of this study was to assess whether differences exist in sagittal alignment between normal controls and patients with spondylolysis or low-grade isthmic spondylolisthesis.

Standing PA and lateral spine radiographs from eighty-two consecutive patients with spondylolysis or low-grade spondylolisthesis (Average age nineteen, range 15–44) were retrospectively compared with those from one hundred and sixty normal volunteers. The films were digitized with a VIDAR scanner and key landmarks were determined. Customized software was then used to measure geometric indices. Pelvic Incidence (PI), Sacral Slope (SS), Pelvic Tilt (PT), and L5-S1extension angle were compared between seventy-two patients with high PI (> 45°) versus ten patients with low PI (< 45°). Average high-PI vs. low-PI values were, respectively: PI (67.32° vs. 43.13°), SS (51.08° vs. 38.05°), PT (16.23° vs. 5.08°), and L5-S1ext (−8.69° vs. −9.57°). Furthermore, the range of values for L5-S1extension in the low-PI subgroup was much narrower (−17.81° to 0.93°) than that for the high-PI subgroup (−31.58° to 38.12°).

This study demonstrates that patients with spondylolysis and low-grade spondylolisthesis have increased Pelvic and L5 incidence, a more vertically oriented L5-S1 intervertebral disc, and less segmental extension between L5 and S1 than patients without radiographic abnormality of the spine. We propose that different mechanisms underlie the etiology of spondylolysis depending on the magnitude of the Pelvic Incidence. These data highlight the importance of seeing localized lumbosacral spine disorders in the context of global alignment of the entire spine and pelvis.

Funding: This research was assisted by support from the Spinal Deformity Study Group

This research was funded by an educational/research grant from Medtronic Sofamor Danek


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 100 - 101
1 Mar 2008
Wu H Poncet P Harder J Cheriet F Labelle H Zernicke R Ronsky J
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The pathogenesis of scoliosis progression remains poorly understood. Seventy-two subject data sets, consisting of four successive values of Cobb-angle and lateral deviations at apices for six and twelve-months intervals in the coronal plane, were used to train and test an artificial neural network (ANN) to predict spinal deformity progression. The accuracies of the trained ANN (3-4-1) for training and testing data were within 3.64° (±2.58°) and 4.40° (±1.86°) of Cobb angles, and within 3.59 (±3.96) mm and 3.98 (±3.41) mm of lateral deviations, respectively. The adapted technique for predicting the scoliosis deformity progression has promising clinical applications.

Scoliosis is a common and poorly understood three-dimensional spinal deformity. The study purpose is to predict scoliosis progression at six and twelve months intervals in the future using successive spinal indices with an artificial neural network (ANN).

The adapted ANN technique enables earlier detection of scoliosis progression with high accuracy. Improved prediction of scoliosis progression will impact bracing or surgical treatment decisions, and may decrease hazardous X-ray exposure.

Seventy-two data sets from adolescent idiopathic scoliosis subjects recruited at the Alberta Children’s Hospital were used in this study. Data sets composed of four successive values of Cobb angles and lateral deviations at apices for six and twelvemonth intervals (coronal plane) were extracted to train and test a specific ANN for predicting scoliosis progression.

Progression patterns in Cobb angles (n = 10) and lateral deviations (n = 8) were successfully identified. The accuracies of the trained ANN (3-4-1) with the training and testing data sets were 3.64° (±2.58°) and 4.40° (±1.86°) of Cobb angles, 3.59 (±3.96) mm and 3.98 (±3.41) mm of lateral deviations, respectively. These results are in close agreement with those using cubic spline extrapolation techniques (3.49° ± 1.85° and 3.31 ± 4.22 mm) and adaptive neuro-fuzzy inference system (3.92° ±3.53° and 3.37 ±3.95 mm) for the same testing data.

ANN can be a promising technique for prediction of scoliosis progression with substantial improvements in accuracy over current techniques, leading to potentially important implications for scoliosis monitoring and treatment decisions.

Funding: AHFMR, CIHR, Fraternal Order of Eagles, NSERC, GEOIDE.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 36 - 36
1 Mar 2008
Grimard G Lacroix G Labelle H Poitras B
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The aim of this study is to compare the adulthood quality of life of subjects with adolescent idiopathic scoliosis who have had surgery to subjects without. Inclusion criteria were being operated or having not operated but having a scoliosis with a Cobb angle ≥ 35° at the last visit. Self-administered questionnaires (five) were sent to all eligible patients. A total of two hundred and four had surgery. The mean Rolland score for subjects was significantly higher for the group who had surgery. The only variable affecting physical component of the SF-36 was the alcohol consumption. The EuroQol score was predicted by the marital status, people being married having a better score. In conclusion, there is not significant difference in the quality of life in adulthood between the subjects with AIS whether they had surgery or not. Subjects who had surgery tend to be less in pain than people not operated on.

The aim of this study is to compare adulthood quality of life of patients with AIS who have had surgery to subjects without.

Overall, there is not significant difference in the quality of life in adulthood between the subjects with AIS whether they had surgery or not. Subjects who had surgery tend to be less in pain than people not operated on.

This preliminary study will help the health professionals involved with the management of patients with AIS make clinical decisions and better understand the long-term quality of life in idiopathic scoliosis.

Among the two hundred and ninety-nine AIS responding, two hundred and four had surgery and ninety-five none and their mean Cobb angle was respectively fifty-eight and forty-four degrees. All patients had a follow up more than twenty years. There was no significant difference as for sex, life status, education, working areas, alcoholism, smoking habits, chronic illness and reproductive health between the two groups. Same proportion of subjects in both groups had no back pain (≅30%); but more non-operated subjects had physiotherapy and/or chiropractic treatments (p< 0.001). The mean Rolland score for subjects was significantly higher for the group who had surgery (p = 0.02). Using multiple regression analysis, the only variable affecting physical component of the quality of life measured with the SF-36 was the alcohol consumption whereas the psychological of the SF-36 was predicted by alcohol consumption as well and the gender. The quality of life measured by the EuroQol was predicted mainly by the marital status, people being married having a better score.

The study was designed as a comparative retrospective cohort study. Subjects referred for Adolescent Idiopathic Scoliosis between 1960 and 1979 to Sainte-Justine Hospital were entered into the cohort. Inclusion criteria were being operated or having not operated but having a scoliosis with a Cobb angle ≥ 35° at the last visit.

A self-administered questionnaire was sent to all eligible patients. The questionnaires that were used were all reliable and valid. More specifically the instruments used were the Oswestry, Roland, SF-36, Quebec Back Pain Disability Scale, Scoliosis Research Society and the EuroQol-5D.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 36 - 36
1 Mar 2008
Mac-Thiong J Labelle H Charlebois M Huot M de Guise J
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This study evaluated the sagittal alignment of the spine and pelvis in adolescent idiopathic scoliosis. The pelvic configuration influenced the lumbar lordosis but was not associated with the thoracic kyphosis or with the curve type. The pelvic incidence in adolescent idiopathic scoliosis was higher than that reported in the literature for normal adolescents and was closer to the values of pelvic incidence found in adults. The role of the PI in the pathogenesis of AIS needs to be explored in a comparative study involving AIS patients and normal adolescents.

The purpose of this study was to evaluate the sagittal alignment of the spine and pelvis in adolescent idiopathic scoliosis (AIS) based on the curve type.

Five sagittal parameters were retrospectively evaluated on lateral radiographs for one hundred and sixty AIS patients: thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). The patients were classified according to their coronal curve type. ANOVA was used to compare the parameters between the curve types and Pearson’s coefficients were used to investigate the relationship between all parameters.

The TK was significantly lower for King I, II and III curves as compared to lumbar curves. The LL was higher for lumbar curves, although not significantly. No significant change between the groups was observed for SS, PT and PI. The PI was significantly correlated to LL, SS and PT for all groups. The LL was strongly related to the SS in all cases but not with the TK, except for thoracolumbar curves.

The TK mostly depended on the spinal deformity while the LL was mainly influenced by the pelvic configuration. The scoliotic curve type was not associated with a specific pattern of sagittal pelvic configuration. The PI was significantly higher than that reported in the literature for normal adolescents.

The role of the PI in the pathogenesis of AIS needs to be explored in a comparative study involving AIS patients and normal adolescents.

Further study is needed to evaluate the prognostic value of the PI in AIS.

Funding: This research was funded by the Canadian Institute of Health Research.

Please contact author for figures and/or diagrams.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 149 - 150
1 Mar 2008
Grimard G Ouellet J Lévesque L Labelle H Poitras B Moreau A Moldovan F Azzedine B Wang D Turgeon I Leclerc S Letellier K Rivard C
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Purpose: Recently, we highlighted a dysfunction in the melatonin signalling pathway in the osteoblasts from adolescent idiopathic scoliosis patients (AIS). The objective of this project is to verify if in the cells coming from the SIA patients, estrogens interfere with melatonin signalling pathways and to identify mechanisms through which these effects are carried out.

Methods: The effects of estrogens on the melatonin signalling pathway, in osteoblasts from AIS patients (n=7), were determined by measuring the capacity of the Gi proteins to inhibit the accumulation of cAMP. The osteoblasts were incubated in the presence of increasing amounts of melatonin (10–11 to 10–5 M) with or without 17-& #946;-estradiol in physiological concentrations (10–10 M) (n=7). Moreover, coimmunoprecipitations using anti-phosphoserine antibodies were carried out and then followed with a Western blot in order to detect melatonin receptors (MT1 and MT2).

Results: The intracellular level of cAMP is higher in the presence of a physiological concentration of 17-& #946;-estradiol among scoliotic patients compared to the level observed in the presence of melatonin alone. Moreover, the preliminary results of the coimmunoprecipitations seem to show an increase in the phosphorylation of proteins interacting with MT1 and MT2 receptors. The precise nature of these proteins remains to be identified.

Conclusions: These results seem to show the antagonistic effects of the 17-& #946;-estradiol on the melatonin signalling pathway in the osteoblasts from AIS patients. However, more cAMP dosages in the presence and absence of 17-& #946;-estradiol are underway so as to increase the number of patients. The results of this study could contribute to the development of the first molecular screening tests as well as the development of new therapeutic approaches.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 101 - 101
1 Mar 2008
Bergeron C Cheriet F Thiong J Labelle H
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This research sought a mathematical model to relate the postero-anterior (PA) and lateral (LAT) views of the spinal curve in scoliosis in an attempt to justify the acquisition of only One X-ray, thereby reducing patient exposure to harmful X-radiation while preserving complete 3D characterization of the spine. Using powerful developments in functional statistics and machine learning, no such relation could be found. Thus, this research sustained the clinical decision to acquire two biplanar X-rays and supported current research in 3D spinal curvature analysis.

Scoliosis is monitored through full spinal X-rays, and this serial protocol causes an increased incidence of cancer development. This research sustains the clinical decision at Hôpital Sainte-Justine in Montréal and elsewhere to acquire postero-anterior (PA) and lateral (LAT) X-rays, despite the increased exposure to X-radiation. Indeed, geometrically, these two views are required to reconstruct the spine in 3D. However, under the assumption of strong physiological patterns between the PA and LAT views of the spinal curve, one of these X-rays may be redundant for some or all patients. The purpose of this study was to seek this a priori assumption.

To this end, a database consisting of three hundred and sixty-nine spinal reconstructions from distinct patients was used. Two powerful geometric modeling approaches were exploited: functional data analysis and minimum noise fractions. These resulted in five comprehensive, uncorrelated and noise-insensitive features in each plane. Simple linear regression yielded no relation that was statistically significant (p< 0.05) and genereralizable to a set of previously unseen samples. Therefore, nonlinear relational modeling was attempted using support vector regression, a recent advance in machine learning theory. This tool was incapable of identifying a robust regression, suggesting that the PA and LAT views are mathematically independent. Thus, this study highlights the necessity of two biplanar X-rays to evaluate scoliotic deformities and fully characterize spinal shape. Further, this study supports the practical insufficiency observed by clinical staff with respect to current 2D scoliosis classifications that has resulted in current efforts to propose 3D classification schemes.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 101 - 101
1 Mar 2008
Mac-Thiong J Labelle H Berthonnaud É Betz RR
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When evaluating and treating patients with spinal disorders, a significant knowledge of the normal spinopelvic balance is of primary importance. This study documents the spinopelvic balance in normal children and adolescents, and describes a scheme of correlations between morphological, shape and orientation parameters of the spine and pelvis. It is found that the pelvic incidence regulates the sacral slope and pelvic tilt. In addition, shape and orientation parameters of adjacent anatomical regions are interdependent, and their relationships result in a stable posture with minimum energy expenditure.

Evaluate the correlations between spinopelvic parameters in normal children and adolescents.

Seven parameters were evaluated from the lateral standing radiographs of two hundred and eighty-two normal subjects aged three to eighteen years old: thoracic kyphosis (TK), thoracic tilt (TT), lumbar lordosis (LL), lumbar tilt (LT), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). Statistical analysis was performed using Pearson’s coefficients.

The mean PI (morphological parameter) was 49.0±11.3°. The mean values for shape parameters were 41.4±8.5°, 48.0±12.0° and 44.3±11.2° for SS, LL and TK, respectively. The mean values for orientation parameters were 7.5±8.1°, −7.0±5.1° and −2.6±5.0° for PT, LT and TT, respectively. There was no significant difference between males and females. PI was significantly related to SS and PT. Significant correlations were found between orientation and shape parameters of adjacent anatomical regions.

This study describes a scheme of correlations between morphological, shape and orientation parameters of the spine and pelvis. It is found that the pelvic incidence regulates the sacral slope and pelvic tilt. In addition, shape and orientation parameters of adjacent anatomical regions are interdependent, and their relationships result in a stable posture with minimum energy expenditure.

This study presents a postural model in order to better understand the spinopelvic balance in normal children and adolescents. This model could help to evaluate the influence of pelvic morphology on the progression and treatment of pediatric spinal deformities.

This research was funded by an educational/research grant from Medtronic Sofamor Danek, by the Canadian Institute of Health Research, by the Fonds de Recherche en Santé du Québec and by the Fondation de recherche et d’éducation en orthopédie de Montréal (FREOM).


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 5 | Pages 646 - 651
1 Sep 1992
Labelle H Guibert R Joncas J Newman N Fallaha M Rivard C

We have reviewed 185 articles published since 1966 to assess the scientific evidence for methods of treatment for lateral epicondylitis of the elbow. Of the 185 articles, 78 discussed treatment, but since the natural history of the syndrome is uncertain we considered only those series with concurrent control groups. Only 18 of these were randomised and controlled studies. We then graded these papers for scientific validity, using the methods of Chalmers et al (1981). The mean score of the 18 articles was only 33%, with a range from 6% to 73%. A minimum of 70% is required for a valid clinical trial, and we therefore concluded that there was insufficient scientific evidence to support any of the current methods of treatment. There were too many methodological differences to allow a quantitative meta-analysis, but our qualitative review established the importance of the natural evolution of the syndrome and of the placebo effect of all treatments. Properly designed, controlled trials are needed.