title: Micro CT Analysis of Spine Architecture in a Mouse Model of Scoliosis.
abstract: OBJECTIVE
  Mice homozygous for targeted deletion of the gene encoding fibroblast growth factor receptor 3 (FGFR3(-/-)) develop kyphoscoliosis by 2 months of age. The first objective of this study was to use high resolution X-ray to characterize curve progression in vivo and micro CT to quantify spine architecture ex vivo in FGFR3(-/-) mice. The second objective was to determine if slow release of the bone anabolic peptide parathyroid hormone related protein (PTHrP-1-34) from a pellet placed adjacent to the thoracic spine could inhibit progressive kyphoscoliosis.
  
  
  METHODS
  Pellets loaded with placebo or PTHrP-1-34 were implanted adjacent to the thoracic spine of 1-month-old FGFR3(-/-) mice obtained from in house breeding. X rays were captured at monthly intervals up to 4 months to quantify curve progression using the Cobb method. High resolution post-mortem scans of FGFR3(-/-) and FGFR3(+/+) spines, from C5/6 to L4/5, were captured to evaluate the 3D structure, rotation, and micro-architecture of the affected vertebrae. Un-decalcified and decalcified histology were performed on the apical and adjacent vertebrae of FGFR3(-/-) spines, and the corresponding vertebrae from FGFR3(+/+) spines.
  
  
  RESULTS
  The mean Cobb angle was significantly greater at all ages in FGFR3(-/-) mice compared with wild type mice and appeared to stabilize around skeletal maturity at 4 months. 3D reconstructions of the thoracic spine of 4-month-old FGFR3(-/-) mice treated with PTHrP-1-34 revealed correction of left/right asymmetry, vertebral rotation, and lateral displacement compared with mice treated with placebo. Histologic analysis of the apical vertebrae confirmed correction of the asymmetry in PTHrP-1-34 treated mice, in the absence of any change in bone volume, and a significant reduction in the wedging of intervertebral disks (IVD) seen in placebo treated mice.
  
  
  CONCLUSIONS
  Local treatment of the thoracic spine of juvenile FGFR3(-/-) mice with a bone anabolic agent inhibited progression of scoliosis, but with little impact on kyphosis. The significant improvement in IVD integrity suggests PTHrP-1-34 might also be considered as a therapeutic agent for degenerative disk disorders.
authors: Bone Engineering Labs, Research Institute-McGill University Health Centre , Montreal, QC , Canada ; Department of Medicine, McGill University , Montreal, QC , Canada.
authors: Chan
authors: C
authors: Gao
authors: Bone Engineering Labs, Research Institute-McGill University Health Centre , Montreal, QC , Canada ; Department of Kinesiology and Physical Education, McGill University , Montreal, QC , Canada.
authors: Brian P
authors: BP
authors: Chen
authors: Bone Engineering Labs, Research Institute-McGill University Health Centre , Montreal, QC , Canada ; Department of Medicine, McGill University , Montreal, QC , Canada.
authors: Michael B
authors: MB
authors: Sullivan
authors: Bone Engineering Labs, Research Institute-McGill University Health Centre , Montreal, QC , Canada ; Biotechnology Program, University of British Columbia , Burnaby, BC , Canada.
authors: Jasmine
authors: J
authors: Hui
authors: Department of Surgery, McGill University , Montreal, QC , Canada.
authors: Jean A
authors: JA
authors: Ouellet
authors: Bone Engineering Labs, Research Institute-McGill University Health Centre , Montreal, QC , Canada ; Department of Medicine, McGill University , Montreal, QC , Canada ; Department of Surgery, McGill University , Montreal, QC , Canada.
authors: Janet E
authors: JE
authors: Henderson
authors: Department of Surgery, McGill University , Montreal, QC , Canada.
authors: Neil
authors: N
authors: Saran
keywords: fibroblast growth factor receptor 3 deficiency; histology; micro-computed tomography; parathyroid hormone-related peptide treatment; progressive kyphoscoliosis; radiography