[Etiopathogenesis of adolescent idiopathic scoliosis and new molecular concepts].

Centre de recherche, CHU Sainte-Justine, Laboratoires de Génétique Moléculaire et de Biologie Cellulaire et Tissulaire des Maladies Musculo-Squelettiques, 3175, chemin de la Côte-Ste-Catherine, Montréal (Québec), H3T 1C5 Canada.
Medecine sciences: M/S (Impact Factor: 0.52). 12/2007; 23(11):910-6. DOI: 10.1051/medsci/20072311910
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Scoliosis is diagnosed as idiopathic in 70 % of structural deformities affecting the spine in children and adolescents, probably reflecting our current misunderstanding of this disease. By definition, a structural scoliosis should be the result of some primary disorder. The goal of this article is to give a comprehensive overview of the currently proposed etiological concepts in idiopathic scoliosis regarding genetics, molecular biology, biomechanics, and neurology, with particular emphasis on adolescent idiopathic scoliosis (AIS). Despite the fact that numerous potential etiologies for idiopathic scoliosis have been formulated, the primary etiology of AIS remains unknown. Beyond etiology, identification of prognostic factors of AIS progression would probably be more relevant in our daily practice, with the hope of reducing repetitive exposure to radiation, unnecessary brace treatments, psychological implications, and costs-of-care related to follow-up in low-risk patients.
    Journal of Children s Orthopaedics 02/2013; 7(1):11-16.
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    ABSTRACT: Idiopathic scoliosis is a three-dimensional deformation of the spine. As its name suggests, its pathogenesis remains poorly understood. Enhanced comprehension of its pathogenesis would be likely to improve current therapeutic results. While the hereditary and genetic origin of scoliosis appears unassailable and several chromosomes are known to be involved in transmission, the role assumed by each individual chromosome remains uncertain, and the mechanisms leading to the expression of scoliosis have yet to be determined. Even though a large number of pathogenetic hypotheses have been put forward and numerous studies carried out, none of these hypotheses have won unanimous approval, and the controversy remains persistent. The objective of this paper is to identify the existing hypotheses and to group them within large-scale etiological categories. We examined the Pubmed and Goggle databases using as keywords "idiopathic scoliosis" and "pathogenesis". The search was limited to articles in English and French. The vicious cycle hypothesis is markedly preponderant. However, no existing pathogenetic model adequately accounts for the formation of scolioses. We are proposing four main pathogenetic mechanisms: asymmetric bone growth dysregulation, susceptibility of bones to deformation, abnormal passive spinal system maintenance and disturbed active spinal system maintenance.
    Annals of physical and rehabilitation medicine 01/2012; 55(2):128-38.
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    ABSTRACT: INTRODUCTION: The association of scoliosis and spondylolisthesis is well documented in literature; the nature and modalities of the relationship of the two pathologies are variable and not always clear. Also, etiologic particulars of scoliosis associated with spondylolisthesis are not well defined, even in cases where scoliosis is called idiopathic. In this paper, we review previous literature and discuss the different aspects of the mutual relationship of scoliosis and spondylolisthesis in the adolescent age. MATERIALS AND METHODS: It is a common notion that the highest occurrence of scoliosis associated with spondylolisthesis is at the lumbar level, both in adolescent and in adult patients. It is probable that the scoliosis that is more heavily determined by the presence of spondylolisthesis is at the lumbar level and presents curve angle lower than 15° Cobb and mild rotation. The scoliosis with curve value over 15° Cobb that is present at the lumbar level in association with spondylolisthesis probably is not prominently due to spondylolisthesis: in these cases, spondylolisthesis is probably only partially responsible for scoliosis progression with a spasm mechanism and/or due to rotation of slipping "olisthetic" vertebra. DISCUSSION: We think that the two pathologies should be treated separately, as stated by many other authors, but we would highlight the concept that, whatever be the scoliosis curve origin, spasm, olisthetic or mixed together, this origin has no influence on treatment. The curves should be considered, for all practical effects, as so-called idiopathic scoliosis. We think that generally patient care should be addressed to treat only spondylolisthesis or only scoliosis, if it is necessary on the basis of clinical findings and therapeutic indications of the isolated pathologies, completely separating the two diseases treatments. CONCLUSIONS: Scoliosis should be considered as an independent disease; only in the case of scoliosis curve progression over time, associated scoliosis must be treated, according to therapeutic principles of the care of any so-called idiopathic scoliosis of similar magnitude, and a similar approach must be applied in the case of spondylolisthesis progression or painful spondylolisthesis.
    European Spine Journal 05/2012; · 2.47 Impact Factor