The inhibitory effect of zoledronate on early-stage osteoinduction by recombinant human bone morphogenetic protein 2 in an osteoporosis model

Growth Factors. 2015;33(3):220-8. doi: 10.3109/08977194.2015.1058259. Epub 2015 Jun 23.

Abstract

This study evaluated the effect of the combined treatment of intravenous zoledronic acid (ZA, 0.08 mg/kg) and rhBMP-2 (5 µg) on osteogenesis in a calvarial defect model of ovariectomized SD rats. New bone formation was evaluated 4 or 8 weeks after calvarial defect implantation using micro-CT and histology. Micro-CT results revealed that the rhBMP-2 group showed significantly higher calvarial defect coverage ratio compared with the ZA + rhBMP-2 group at 4 weeks. In addition, bone formation indices were significantly lower in ZA + rhBMP-2 group when compared with the rhBMP-2 group after 4 weeks, which indicates a negative effect of ZA on the initial bone formation and the bone quality. At 8 weeks, the negative effect induced by ZA treatment was alleviated as time passed. Histological examination showed similar results to the micro-CT measurements. In conclusion, although ZA treatment lowered the new bone formation induced by rhBMP-2 initially, as time passed, the negative effect was decreased.

Keywords: Bone morphogenetic protein-2; calvarial defect model; osteogenesis; zoledronic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Bone Remodeling / drug effects
  • Diphosphonates / therapeutic use*
  • Disease Models, Animal
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Osteogenesis / drug effects*
  • Osteoporosis / drug therapy*
  • Osteoporosis / pathology
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / therapeutic use
  • Skull / metabolism*
  • Skull / surgery
  • Transforming Growth Factor beta / therapeutic use*
  • Wound Healing / drug effects
  • X-Ray Microtomography
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Bone Morphogenetic Protein 2
  • Diphosphonates
  • Imidazoles
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Zoledronic Acid