Pathogenesis of progressive adolescent idiopathic scoliosis. Platelet activation and vascular biology in immature vertebrae: an alternative molecular hypothesis.
Altered paraspinal muscle activity was suggested by Lowe et al (2002) to explain a relationship between Cobb angle changes and platelet calmodulin level changes in adolescent idiopathic scoliosis (AIS). We formulate an alternative platelet-skeletal hypothesis which involves: (1) a small scoliosis curve; (2) axial loads transmitted directly from the intervertebral discs to vertebral body growth plates (endplate physes) as axial inward bulges that create mechanical micro-insults; (3) the latter cause dilatation of juxta-physeal vessels and, in deforming vertebrae, vascular damage with exposure of subendothelial collagen and other agonist proteins; (4) subject to predisposition, platelet activation with calmodulin changes occurs within dilated vessels of deforming vertebral bodies; (5) the activated platelets in juxta-physeal vessels release growth factors that, after extravasation, abet the hormone-driven growth of the already mechanically-compromised vertebral endplate physes to promote the relative anterior spinal overgrowth and curve progression of AIS. The hypothesis links several fields in each of which research within ethical restraints is suggested to refute it.
Burwell
Richard Geoffrey
RG
The Centre for Spinal Studies and Surgery, University Hospital Nottingham, United Kingdom. burwell@bun.com
Dangerfield
Peter Hugh
PH
D000293:Adolescent; D001792:Blood Platelets / Q000378:metabolism; D002147:Calmodulin / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism; D006728:Hormones / Q000502:physiology; D006801:Humans; D015539:Platelet Activation / Q000502:physiology*; D012600:Scoliosis / Q000209:etiology*; D013131:Spine / Q000502:physiology*; D013314:Stress, Mechanical
D002147:Calmodulin; D006133:Growth Substances; D006728:Hormones