Calcified Tissue International

, Volume 80, Issue 4, pp 259–267

Bone Formation Zones in Heterotopic Ossifications: Histologic Findings and Increased Expression of Bone Morphogenetic Protein 2 and Transforming Growth Factors ß2 and ß3


    • Clinic of Traumatology and OrthopedicsUniversity of Tartu
  • A. Arend
    • Department of AnatomyUniversity of Tartu
  • D. Gunnarsson
    • Department of Molecular BiologyUmeå University
  • R. Ulfsparre
    • Department of Molecular BiologyUmeå University
  • S. Suutre
    • Department of AnatomyUniversity of Tartu
  • T. Haviko
    • Clinic of Traumatology and OrthopedicsUniversity of Tartu
  • G. Selstam
    • Department of Molecular BiologyUmeå University

DOI: 10.1007/s00223-007-9000-x

Cite this article as:
Toom, A., Arend, A., Gunnarsson, D. et al. Calcif Tissue Int (2007) 80: 259. doi:10.1007/s00223-007-9000-x


Heterotopic ossifications (HOs) formed after total endoprosthetic replacement of the hip joint were collected during revision surgery (n = 7). Tissues collected during regular hip arthroplasty (n = 12) were used as reference. Histomorphometric analysis was performed for assessment of bone formation activity in HOs and reference bone. HOs were dissected with histological guidance into three zones: formed bone, zone of active bone formation, and zone with fibrous connective and fibrocartilagineous tissue. Relative expression of the mRNA for bone morphogenetic protein 2 (BMP-2), transforming growth factor ß2 (TGF-ß2), and TGF-ß3 was determined by reverse-transcription polymerase chain reaction relative to ß-actin. Expression of all three growth factors was higher than in orthotopic bone. Similarly, the osteoid surface density was increased in HOs. The levels of all growth factors were higher in the zone of active bone formation or remodeling than in the zone of formed bone. In matured HOs, the osteoid surface density as well as mRNA levels were lower, although still significantly raised, indicating that bone formation slows down after 2 years. Immunohistochemical analysis demonstrated the presence of TGF-ß1, TGF-ß2, TGF-ß3, and BMP-2 proteins in the zone of bone formation. We conclude that bone formation after heterotopic bone induction is initially intense, slows down within 2 years, and thereupon continues as active remodeling mainly on the border of HO. Our data indicate that BMP-2, TGF-ß2, and TGF-ß3 are involved in bone formation in HO.


Bone formation zoneHeterotopic ossificationTotal hip arthroplastyBone morphogenetic protein 2Transforming growth factors ß2 and ß3

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© Springer Science+Business Media, LLC 2007