Type V osteogenesis imperfecta: a new form of brittle bone disease

J Bone Miner Res. 2000 Sep;15(9):1650-8. doi: 10.1359/jbmr.2000.15.9.1650.

Abstract

Osteogenesis imperfecta (OI) is commonly subdivided into four clinical types. Among these, OI type IV clearly represents a heterogeneous group of disorders. Here we describe 7 OI patients (3 girls), who would typically be classified as having OI type IV but who can be distinguished from other type IV patients. We propose to call this disease entity OI type V. These children had a history of moderate to severe increased fragility of long bones and vertebral bodies. Four patients had experienced at least one episode of hyperplastic callus formation. The family history was positive for OI in 3 patients, with an autosomal dominant pattern of inheritance. All type V patients had limitations in the range of pronation/supination in one or both forearms, associated with a radiologically apparent calcification of the interosseous membrane. Three patients had anterior dislocation of the radial head. A radiodense metaphyseal band immediately adjacent to the growth plate was a constant feature in growing patients. Lumbar spine bone mineral density was low and similar to age-matched patients with OI type IV. None of the type V patients presented blue sclerae or dentinogenesis imperfecta, but ligamentous laxity was similar to that in patients with OI type IV. Levels of biochemical markers of bone metabolism generally were within the reference range, but serum alkaline phosphatase and urinary collagen type I N-telopeptide excretion increased markedly during periods of active hyperplastic callus formation. Qualitative histology of iliac biopsy specimens showed that lamellae were arranged in an irregular fashion or had a meshlike appearance. Quantitative histomorphometry revealed decreased amounts of cortical and cancellous bone, like in OI type IV. However, in contrast to OI type IV, parameters that reflect remodeling activation on cancellous bone were mostly normal in OI type V, while parameters reflecting bone formation processes in individual remodeling sites were clearly decreased. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations affecting glycine codons or splice sites. In conclusion, OI type V is a new form of autosomal dominant OI, which does not appear to be associated with collagen type I mutations. The genetic defect underlying this disease remains to be elucidated.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alkaline Phosphatase / blood
  • Biomarkers
  • Birth Weight
  • Body Weight
  • Bone Density
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology*
  • Child
  • Child, Preschool
  • Female
  • Fibroblasts
  • Genes, Dominant
  • Humans
  • Hyperplasia / pathology
  • Infant, Newborn
  • Karyotyping
  • Male
  • Mutation
  • Osteogenesis Imperfecta / classification*
  • Osteogenesis Imperfecta / diagnostic imaging
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / pathology*
  • Radiography
  • Terminology as Topic

Substances

  • Biomarkers
  • Alkaline Phosphatase