title: Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs.
abstract: BACKGROUND
  Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient α-l-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disk degeneration, leading to spinal cord compression and kypho-scoliosis. The objective of this study was to establish the nature and rate of progression of cervical vertebral bone disease in MPS I using a canine model.
  
  
  METHODS
  C2 vertebrae were obtained post-mortem from normal and MPS I dogs at 3, 6 and 12 months-of-age. Morphometric parameters and mineral density for the vertebral trabecular bone and odontoid process were determined using micro-computed tomography. Vertebrae were then processed for paraffin histology, and cartilage area in both the vertebral epiphyses and odontoid process were quantified.
  
  
  RESULTS
  Vertebral bodies of MPS I dogs had lower trabecular bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) than normals at all ages. For MPS I dogs, BV/TV, Tb.Th and BMD plateaued after 6 months-of-age. The odontoid process appeared morphologically abnormal for MPS I dogs at 6 and 12 months-of-age, although BV/TV and BMD were not significantly different from normals. MPS I dogs had significantly more cartilage in the vertebral epiphyses at both 3 and 6 months-of-age. At 12 months-of-age, epiphyseal growth plates in normal dogs were absent, but in MPS I dogs they persisted.
  
  
  CONCLUSIONS
  In this study we report reduced trabecular bone content and mineralization, and delayed cartilage to bone conversion in MPS I dogs from 3 months-of-age, which may increase vertebral fracture risk and contribute to progressive deformity. The abnormalities of the odontoid process we describe likely contribute to increased incidence of atlanto-axial subluxation observed clinically. Therapeutic strategies that enhance bone formation may decrease incidence of spine disease in MPS I patients.
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Chiaro
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Baron
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Del Alcazar
authors.forename: Patricia
authors.initials: P
authors.lastname: O'Donnell
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Elliott
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Ponder
authors.forename: Mark E
authors.initials: ME
authors.lastname: Haskins
authors.forename: Lachlan J
authors.initials: LJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000000981:diagnostic imaging / Q000473:pathology; D002574:Cervical Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D004285:Dogs; D008059:Mucopolysaccharidosis I / Q000000981:diagnostic imaging / Q000473:pathology*; D009809:Odontoid Process / Q000000981:diagnostic imaging / Q000473:pathology; D013122:Spinal Diseases / Q000000981:diagnostic imaging / Q000473:pathology*; D014057:Tomography, X-Ray Computed
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