Progressive spinal deformities (notably scoliosis and spondylolisthesis) progress most rapidly during the adolescent growth spurt. In scoliosis (including neuromuscular, congenital and idiopathic forms) this progression involves increasing wedging deformity of the vertebrae and discs in the coronal plane, together with lesser magnitudes of deformity in other planes. While it appears that mechanically modulated endochondral growth is responsible in large part for the progressive vertebral wedging, the mechanism by which intervertebral discs become increasingly deformed is largely unknown and probably very different, since there is minimal growth of intervertebral discs accompanying adolescent vertebral growth. The proposed studies will determine how intervertebral discs respond to the altered stress that occurs in a skeletally immature spine with scoliosis. A skeletally immature rat tail model that has demonstrated vertebral wedging as seen in scoliosis will be extended to determine the changes in the intervertebral disc with angulation deformity and compressive loading. Three permutations of sustained compression and sustained angulation for up to 5 weeks will be compared. Loaded and/or deformed and adjacent control discs will be measured to determine morphological, structural and mechanical changes, annulus tissue composition (including convex and concave sides), protein synthesis and cellularity. Protein synthesis will be evaluated along with gene expression for major proteins involved in synthesis and degradation of disc tissue. The findings will be interpreted with reference to the overall hypothesis that the intervertebral disc component of scoliosis progression results from mechanically-mediated remodelling and degeneration of the intervertebral disc on the concave side, which is chronically more heavily loaded. The major challenges in designing early interventions clinically to prevent scoliosis progression are the unknown mechanisms of scoliosis progression during adolescence and absence of accurate tests to identify potentially progressive deformities (prognosis). The proposed work provide improved understanding of deformity progression to permit design of novel therapeutic approaches to restore symmetrical growth of the spine. These approaches may include improvements in brace design, new possibilities for muscle rehabilitation, and surgical procedures aimed at early, minimally invasive modification of spinal growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR053132-04
Application #
7647095
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2006-09-01
Project End
2010-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$318,209
Indirect Cost
Name
University of Vermont & St Agric College
Department
Orthopedics
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Stokes, Ian A F; McBride, Carole; Aronsson, David D et al. (2013) METABOLIC EFFECTS OF ANGULATION, COMPRESSION AND REDUCED MOBILITY ON ANNULUS FIBROSIS IN A MODEL OF ALTERED MECHANICAL ENVIRONMENT IN SCOLIOSIS. Spine Deform 1:161-170
Stokes, Ian A F; McBride, Carole; Aronsson, David D et al. (2011) Intervertebral disc changes with angulation, compression and reduced mobility simulating altered mechanical environment in scoliosis. Eur Spine J 20:1735-44
Aronsson, David D; Stokes, Ian A F (2011) Nonfusion treatment of adolescent idiopathic scoliosis by growth modulation and remodeling. J Pediatr Orthop 31:S99-106
Stokes, Ian A F; Sangole, Archana P; Aubin, Carl-Eric (2009) Classification of scoliosis deformity three-dimensional spinal shape by cluster analysis. Spine (Phila Pa 1976) 34:584-90
Will, Ryan E; Stokes, Ian A; Qiu, Xing et al. (2009) Cobb angle progression in adolescent scoliosis begins at the intervertebral disc. Spine (Phila Pa 1976) 34:2782-6
Villemure, Isabelle; Stokes, Ian A F (2009) Growth plate mechanics and mechanobiology. A survey of present understanding. J Biomech 42:1793-803
Stokes, I A F; McBride, C A; Aronsson, D D (2008) Intervertebral disc changes in an animal model representing altered mechanics in scoliosis. Stud Health Technol Inform 140:273-7
Stokes, I A F (2008) Stature and growth compensation for spinal curvature. Stud Health Technol Inform 140:48-51
Stokes, Ian A F (2008) Mechanical modulation of spinal growth and progression of adolescent scoliosis. Stud Health Technol Inform 135:75-83