L’effet des différents facteurs de croissance sur la viabilité et la prolifération des ostéoblastes scoliotiques

Résumé: La Scoliose Idiopathique de l’Adolescent (SIA) est une condition débilitante qui peut avoir comme résultat une douleur importante, une altération du fonctionnement quotidien et une détérioration de la qualité de vie. Pour les patients qui ne répondent pas au traitement conservateur, la fusion vertébrale, en utilisant des greffes osseuses, est devenue un traitement de choix pour stabiliser la colonne. Des connaissances plus pointues à propos des facteurs impliqués dans l’ostéogénèse et la formation de l’os peuvent raccourcir le processus de guérison et permettre aux patients de réintégrer leurs activités dans un laps de temps plus court. Les plaquettes peuvent jouer un rôle important dans la première étape de la guérison des fractures car elles sont une source autologue de plusieurs facteurs de croissance qui soutiennent la prolifération et la différenciation des ostéoblastes in vivo et in vitro. Au cours des dernières années, plusieurs tentatives ont été réalisées afin de trouver des traitements additionnels pour : 1) Raccourcir le temps de guérison des fractures relativement long ; 2) Obtenir une plus courte période de convalescence pour les patients qui ont besoin de prothèses ; 3) Corriger plus facilement plusieurs maladies congénitales; 4) Améliorer le processus de fusion vertébrale et 5) Développer de nouvelles approches thérapeutiques, notamment au niveau des processus régularisant le remodelage osseux et la régénération des tissus osseux. Dans le cadre de la présente étude, j’ai étudié la contribution possible du facteur de croissance de l’insuline (IGF) et du facteur vasculaire endothélial de croissance (VEGF) sur la maturation de l’ostéoblaste scoliotique dans des cultures cellulaires in vitro et j’ai comparé les résultats avec celles obtenues dans les mêmes conditions mais en stimulant les ostéoblastes avec de la mélatonine. Cette étude préliminaire a été réalisée sur des échantillons d’os récoltés de quatre patients atteints par la Scoliose Idiopathique de l‘Adolescent (SIA), ainsi que sur des échantillons d’os issus de quatre sujets témoins (cas traumatiques). Les résultats montrent que l’IGFs et le VEGFs possèdent une action d’inhibition sur la prolifération d’ostéoblastes scoliotiques et non scoliotiques, et que cette action est proportionnelle à la concentration de ces facteurs. Les ostéoblastes scoliotiques tendent à avoir une prolifération cellulaire plus rapide et plus élevée que les témoins non scoliotiques. De façon générale les ostéoblastes provenant de patients scoliotiques ont une ostéogénèse in vitro plus accélérée que le sujet non scoliotique. De plus, il semble que la mélatonine joue un rôle physiologique dans la différenciation de l’ostéoblaste scoliotique et elle semble aider à avoir une différenciation plus précoce que chez les non traités. Les ostéoblastes scoliotiques expriment un défaut d’expression de l’IGF 1 et d’IGF 1R en présence de la mélatonine. En conclusion, le VEGF A et l’IGF 1 peuvent également promouvoir la différenciation et la prolifération des ostéoblastes humains scoliotiques en culture primaire.Abstract: The Adolescent Idiopathic Scoliosis (AIS) is a debilitating condition and as a result often produces significant pain, impaired daily functioning and a deterioration of the quality of life. For patients who do not respond to conservative treatment, spinal fusion using bone grafts has become a treatment of choice to stabilize the spine. The more accurate knowledge of the factors involved in osteogenesis and the bone formation can shorten the healing process and reintegrate patients into their daily activities in a shorter period of time. Platelets can play an important role in the first stage of the healing of fractures and they are a source of several autologous growth factors that support the proliferation and differentiation of osteoblasts in vivo and in vitro. A wide variety of techniques and approaches have been investigated for performing spinal fusion, yet surgeons continue to investigate alternative methods with the goal of improving surgical outcome and minimizing morbidity. We can use these methods to: 1.Reduce the relatively long time needed for healing fractures 2. Patients with prosthesis could benefit of a shorter convalescent time 3. Several congenital diseases could be easier to correct and 4. We could stimulate the vertebral fusion 5. Develop new therapeutic techniques, including that of the processes regulating bone remodelling and regeneration of bone tissue. In the present study, we tried to find whether the insulin growth factor (IGF) and the vascular endothelial growth factor (VEGF) have an influence on the scoliotic osteoblasts in vitro cell cultures and we compared the results with those obtained in the same condition but by stimulating osteoblasts with melatonin. This preliminary study was performed on osteoblasts cultured from four patients affected by Adolescent Idiopathic Scoliosis (AIS) and four controls. In all cases of AIS, bone specimens were obtained from the vertebral body or spinous process (in accordance with the surgical procedure performed). Our results show that IGFs as well as VEGF have an inhibitive effect on the proliferation of scoliotic and non-scoliotic cells and the effect is proportional with the growth factor concentration. In general osteoblasts cultured from scoliotic patients have an in vitro osteogenesis quicker than the subject without scoliosis. Moreover, it appears that melatonin plays a physiological role in the differentiation of scoliotic osteoblasts and it appears to help differentiate earlier than in the untreated group. We found that the expression of IGF 1 and IGF 1R in scoliotic osteoblasts was impaired in the presence of melatonin. In conclusion, VEGF A and IGF both can influence the cell differentiation and proliferation of human scoliotic osteoblasts in primary cell culture

SpineCor treatment for Juvenile Idiopathic Scoliosis: SOSORT award 2010 winner

<p>Introduction</p> <p>Juvenile idiopathic scoliosis is a condition used to describe patients who are least 4 years of age but younger than 10 when the deformity is first identified. In these patients, the condition is usually progressive and those that are diagnosed at five years or younger have a high chance of progression to a large curve, with additional pulmonary and cardiac complications. The main form of conservative treatment for juvenile scoliosis is the use of a bracing system. This prospective interventional study was conducted to evaluate the effectiveness of the Dynamic SpineCor orthosis for juvenile idiopathic scoliosis as well as to evaluate the stability of the spine after the weaning point.</p> <p>Material and Methods</p> <p>For this study, 150 juvenile patients were treated by the SpineCor orthosis between 1993 and 2009. Of these, 67 patients had a definite outcome and 83 are still actively being treated. To determine the effectiveness of the brace the <b>OUTCOME </b>criteria recommended by the SRS was used.</p> <p>Results</p> <p>The results from our study showed that of the 67 patients with a definite outcome, 32.9% corrected their Cobb angle by at least 5° and 10.5% had a stabilization of their Cobb angle. Within the patients with a definite outcome, 37.3% of patients where recommended for surgery before authorized end of treatment. For this group of patients, surgery was postponed. Looking at the stability of the curves 2 years after the end of the treatment, we found 12.5% of the patients continued their correction without the brace being used and 71.4% remained stable.</p> <p>Discussion</p> <p><b>From our study we can clearly see that the effectiveness of the SpineCor orthosis in obtaining and maintaining the neuromuscular integration of the corrective movement can be achieved effectively for juvenile patients</b>. Over 75% of all patients that finished the treatment had remained stable with a few continuing to correct their Cobb angle after the use of the SpineCor orthosis was discontinued.</p> <p>Conclusion</p> <p>Our conclusion from this study is that the SpineCor orthosis is a very effective method of treatment of juvenile idiopathic scoliosis. The results obtained also indicate that treatment outcomes are better with early bracing. Most encouraging perhaps is the fact that the positive outcome appears to be maintained in the long term, and that surgery can be avoided or at least postponed.</p

2011 SOSORT guidelines: Orthopaedic and Rehabilitation treatment of idiopathic scoliosis during growth

<p>Abstract</p> <p>Background</p> <p>The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT), that produced its first Guidelines in 2005, felt the need to revise them and increase their scientific quality. The aim is to offer to all professionals and their patients an evidence-based updated review of the actual evidence on conservative treatment of idiopathic scoliosis (CTIS).</p> <p>Methods</p> <p>All types of professionals (specialty physicians, and allied health professionals) engaged in CTIS have been involved together with a methodologist and a patient representative. A review of all the relevant literature and of the existing Guidelines have been performed. Documents, recommendations, and practical approach flow charts have been developed according to a Delphi procedure. A methodological and practical review has been made, and a final Consensus Session was held during the 2011 Barcelona SOSORT Meeting.</p> <p>Results</p> <p>The contents of the document are: methodology; generalities on idiopathic scoliosis; approach to CTIS in different patients, with practical flow-charts; literature review and recommendations on assessment, bracing, physiotherapy, Physiotherapeutic Specific Exercises (PSE) and other CTIS. Sixty-five recommendations have been given, divided in the following topics: Bracing (20 recommendations), PSE to prevent scoliosis progression during growth (8), PSE during brace treatment and surgical therapy (5), Other conservative treatments (3), Respiratory function and exercises (3), Sports activities (6), Assessment (20). No recommendations reached a Strength of Evidence level I; 2 were level II; 7 level III; and 20 level IV; through the Consensus procedure 26 reached level V and 10 level VI. The Strength of Recommendations was Grade A for 13, B for 49 and C for 3; none had grade D.</p> <p>Conclusion</p> <p>These Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method. According to results, it is possible to understand the lack of research in general on CTIS. SOSORT invites researchers to join, and clinicians to develop good research strategies to allow in the future to support or refute these recommendations according to new and stronger evidence.</p