Effect of bone morphogenetic protein-2, demineralized bone matrix and systemic parathyroid hormone (1-34) on local bone formation in a rat calvaria critical-size defect model

J Periodontal Res. 2013 Apr;48(2):243-51. doi: 10.1111/jre.12001. Epub 2012 Sep 13.

Abstract

Aim: To determine the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) soak-loaded on to an absorbable collagen sponge (ACS) to induce local bone formation compared with the clinical reference demineralized bone matrix (DBM) and to investigate potential additive/synergistic effects of exogenous parathyroid hormone (PTH).

Methods: Critical-size (8 mm), through-through calvaria osteotomy defects in 160 adult male Sprague-Dawley rats were randomized to receive one of eight interventions: rhBMP-2/ACS, DBM, ACS, or serve as controls (empty defects) combined or not with systemic PTH. Ten animals from each group were followed for 4 and 8 wks for radiographic and histometric analysis. Multivariable analysis was used to assess the effect of experimental intervention and healing time on local bone formation.

Results: In the multivariable analysis, rhBMP-2/ACS exhibited significantly greater histologic bone formation than control (β ± SE: 54.76 ± 5.85, p < 0.001) and ACS (β ± SE: 9.14 ± 3.31, p = 0.007) whereas DBM showed significantly less bone formation than control (β ± SE: -32.32 ± 8.23, p < 0.001). Overall, PTH did not show a significant effect on bone formation (β ± SE: 2.72 ± 6.91, p = 0.70). No significant differences in histological defect closure were observed between 4 and 8 wks for all but the control group without PTH.

Conclusion: rhBMP-2/ACS significantly stimulates local bone formation whereas bone formation appears significantly limited by DBM. Systemic application of PTH provided no discernible additive/synergistic effects on local bone formation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Absorbable Implants
  • Animals
  • Bone Demineralization Technique
  • Bone Diseases / diagnostic imaging
  • Bone Diseases / surgery*
  • Bone Matrix / transplantation*
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Collagen
  • Craniotomy / methods
  • Drug Carriers
  • Drug Synergism
  • Humans
  • Male
  • Microscopy, Polarization
  • Osteogenesis / drug effects
  • Parathyroid Hormone / therapeutic use*
  • Radiography
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / therapeutic use
  • Skull / diagnostic imaging
  • Skull / drug effects*
  • Time Factors
  • Tissue Preservation / methods
  • Transforming Growth Factor beta / therapeutic use*
  • Wound Healing / drug effects

Substances

  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Parathyroid Hormone
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Collagen