Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation

J Bone Miner Res. 2017 Sep;32(9):1884-1892. doi: 10.1002/jbmr.3180. Epub 2017 Jun 26.

Abstract

In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research.

Keywords: BISPHOSPHONATE TREATMENT; MATRIX MINERALIZATION; OSTEOCYTE LACUNAE; OSTEOGENESIS IMPERFECTA TYPE V; QUANTITATIVE BACKSCATTERED ELECTRON IMAGING.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Bone Density* / drug effects
  • Bone Density* / genetics
  • Calcinosis* / diagnostic imaging
  • Calcinosis* / drug therapy
  • Calcinosis* / genetics
  • Calcinosis* / metabolism
  • Cancellous Bone / diagnostic imaging
  • Cancellous Bone / metabolism
  • Child
  • Child, Preschool
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Cortical Bone / diagnostic imaging
  • Cortical Bone / metabolism
  • Diphosphonates / administration & dosage*
  • Female
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Osteocytes* / metabolism
  • Osteocytes* / pathology
  • Osteogenesis Imperfecta* / diagnostic imaging
  • Osteogenesis Imperfecta* / drug therapy
  • Osteogenesis Imperfecta* / genetics
  • Osteogenesis Imperfecta* / metabolism
  • Osteogenesis* / drug effects
  • Osteogenesis* / genetics
  • Pamidronate

Substances

  • COL1A2 protein, human
  • Collagen Type I
  • Diphosphonates
  • IFITM5 protein, human
  • Membrane Proteins
  • collagen type I, alpha 1 chain
  • Pamidronate

Supplementary concepts

  • Osteogenesis imperfecta, type 2A