Intraosseous BMP implants in rabbits. Inhibitory effect on bone formation

Acta Orthop Scand. 1999 Feb;70(1):77-83. doi: 10.3109/17453679909000963.

Abstract

The bone harvest chamber is a model for rapid spontaneous bone healing in rabbits. We have previously shown inhibition of bone formation by using BMP-2 on a collagen carrier in this intraosseous model, despite bone formation when depositing BMP-2 on a similar carrier subfascially in the same animals. The doses were 12 and 0.6 micrograms/5 mm3 chamber volume. As these findings conflicted with most other experiments dealing with the skeletal response to BMP-2, we repeated the previous experiments with variations. We studied: 1) a lower BMP-2 dose, 2) a different type of BMP (BMP-7/OP-1), 3) a different carrier (hydroxyapatite), 4) a different chamber construction allowing contact with extraskeletal tissue and 5) BMP-2 on the original collagen carrier in an acutely inserted chamber in rats. We also studied the border between the BMP-2 implant and the preexisting bone to see whether BMP-2 caused premature differentiation of the callus so that proliferation was stopped and a bone cyst formed. The low dose of BMP-2 reduced tissue ingrowth and tended to reduce bone formation. BMP-7 showed the same inhibitory effects as BMP-2. BMP-2 on a hydroxyapatite carrier also inhibited bone formation in the chamber. In the chamber that allowed contact with extraskeletal tissue, we observed no effects of BMP-2. The border between the BMP-2 implant and the preexisting bone did not look like a cyst wall. BMP-2, from the same batch, on a similar collagen carrier, regularly increased bone formation in the acutely inserted bone chamber in rats, thereby excluding major defects in the BMP-2 implants. The inhibition in this specific model is a consistent finding and not due to an overdose, a specific BMP-type, a specific carrier or premature callus differentiation.

Publication types

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

MeSH terms

  • Animals
  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bony Callus / drug effects
  • Collagen
  • Drug Carriers
  • Drug Evaluation, Preclinical
  • Drug Implants
  • Durapatite
  • Osteogenesis / drug effects*
  • Rabbits
  • Rats
  • Transforming Growth Factor beta*

Substances

  • Biocompatible Materials
  • Bmp2 protein, rat
  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Drug Carriers
  • Drug Implants
  • Transforming Growth Factor beta
  • Collagen
  • Durapatite