Predicting growth and curve progression in the individual patient with adolescent idiopathic scoliosis: design of a prospective longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>Scoliosis is present in 3-5% of the children in the adolescent age group, with a higher incidence in females. Treatment of adolescent idiopathic scoliosis is mainly dependent on the progression of the scoliotic curve. There is a close relationship between curve progression and rapid (spinal) growth of the patient during puberty. However, until present time no conclusive method was found for predicting the timing and magnitude of the pubertal growth spurt in total body height, or the curve progression of the idiopathic scoliosis.</p> <p>The goal of this study is to determine the predictive value of several maturity indicators that reflect growth or remaining growth potential, in order to predict timing of the peak growth velocity of total body height in the individual patient with adolescent idiopathic scoliosis. Furthermore, different parameters are evaluated for their correlation with curve progression in the individual scoliosis patient.</p> <p>Methods/design</p> <p>This prospective, longitudinal cohort study will be incorporated in the usual care of patients with adolescent idiopathic scoliosis. All new patients between 8 and 17 years with adolescent idiopathic scoliosis (Cobb angle >10 degrees) visiting the outpatient clinic of the University Medical Center Groningen are included in this study. Follow up will take place every 6 months. The present study will use a new ultra-low dose X-ray system which can make total body X-rays. Several maturity indicators are evaluated like different body length dimensions, secondary sexual characteristics, skeletal age in hand and wrist, skeletal age in the elbow, the Risser sign, the status of the triradiate cartilage, and EMG ratios of the paraspinal muscle activity.</p> <p>Correlations of all dimensions will be calculated in relationship to the timing of the pubertal growth spurt, and to the progression of the scoliotic curve. An algorithm will be made for the optimal treatment strategy in the individual patient with adolescent idiopathic scoliosis.</p> <p>Discussion</p> <p>This study will determine the value of many maturity indicators and will be useful as well for other clinicians treating children with disorders of growth. Since not all clinicians have access to the presented new 3D X-ray system or have the time to make EMG's, for example, all indicators will be correlated to the timing of the peak growth velocity of total body height and curve progression in idiopathic scoliosis. Therefore each clinician can chose which indicators can be used best in their practice.</p> <p>Trial registration number</p> <p>NTR2048</p

Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis

Asymmetrical growth of the vertebrae has been implicated as one possible etiologic factor in the pathogenesis of adolescent idiopathic scoliosis. The longitudinal vertebral growth derives from the endochondral ossification of the vertebral growth plate. In the present study, the growth plates from the convex and concave side of the vertebrae were characterized by the method of histology and immunohistochemistry to evaluate the growth activity, cell proliferation, and apoptosis. Normal zoned architectures were observed in the convex side of the growth plate and disorganized architectures in the concave side. The histological grades were significantly different between the convex and the concave side of the growth plate in the apex vertebrae (P < 0.05). The histological difference was also found significant statistically between end vertebrae and apex vertebrae in the concave side of vertebral growth plates (P < 0.05). The proliferative potential indexes and apoptosis indexes of chondrocytes in the proliferative and hypertrophic zone in the convex side were significantly higher than that in the concave side in the apex vertebral growth plate (P < 0.05). There was a significant difference of the proliferative potential index (proliferating cell nuclear antigen, PCNA index) between convex side and concave side at the upper end vertebra (P < 0.05). The difference of the proliferative potential index and apoptosis index were found significant statistically in the concave side of the vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). The same result was also found for the apoptosis index (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling assay, TUNEL index) in the convex side of vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). Some correlation were found between radiographic measurements and proliferation and apoptosis indexes. The difference in histological grades and cellular activity between the convex and concave side indicated that the bilateral growth plate of the vertebrae in AIS patients have different growth kinetics which may affect the curve progression

Differential Proteome Analysis of Bone Marrow Mesenchymal Stem Cells from Adolescent Idiopathic Scoliosis Patients

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. The cause and pathogenesis of scoliosis and the accompanying generalized osteopenia remain unclear despite decades of extensive research. In this study, we utilized two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) to analyze the differential proteome of bone marrow mesenchymal stem cells (BM-MSCs) from AIS patients. In total, 41 significantly altered protein spots were detected, of which 34 spots were identified by MALDI-TOF/TOF analysis and found to represent 25 distinct gene products. Among these proteins, five related to bone growth and development, including pyruvate kinase M2, annexin A2, heat shock 27 kDa protein, γ-actin, and β-actin, were found to be dysregulated and therefore selected for further validation by Western blot analysis. At the protein level, our results supported the previous hypothesis that decreased osteogenic differentiation ability of MSCs is one of the mechanisms leading to osteopenia in AIS. In summary, we analyzed the differential BM-MSCs proteome of AIS patients for the first time, which may help to elucidate the underlying molecular mechanisms of bone loss in AIS and also increase understanding of the etiology and pathogenesis of AIS