Dose-Dependent Resorption of Allograft by rhBMP-2 Uncompensated by New Bone Formation-A Canine Study With Implants and Zoledronate

J Arthroplasty. 2018 Apr;33(4):1215-1221.e1. doi: 10.1016/j.arth.2017.11.019. Epub 2017 Nov 16.

Abstract

Background: Impacted bone allograft is used to restore lost bone in total joint arthroplasties. Bone morphogenetic proteins (BMPs) can induce new bone formation to improve allograft incorporation, but they simultaneously invoke a seemingly dose-dependent allograft resorption mediated by osteoclasts. Bisphosphonates effectively inhibit osteoclast activity. Predicting allograft resorption when augmented with bone morphogenetic protein 2 (BMP-2), we intended to investigate whether a balanced bone metabolism was achievable within a range of BMP-2 doses with systemic zoledronate treatment.

Methods: Implants were coated with 1 of 3 BMP-2 doses (15 μg, 60 μg, and 240 μg) or left untreated. Implants were surrounded by a 2.5-mm gap filled with impacted morselized allograft. Each of the 12 dogs included received 1 of each implant (15 μg, 60 μg, 240 μg, and untreated), 2 in each proximal humerus. During the 4-week observation period, zoledronate intravenous (0.1 mg/kg) was administered to all animals 10 days after surgery as anticatabolic treatment. Implant osseointegration was evaluated by histomorphometry and mechanical push-out tests.

Results: Untreated implants had the best mechanical fixation and superior retention of allograft as compared to any of the BMP-2 implants. Both mechanical implant fixation and retention of allograft decreased significantly with BMP-2 dose increments. Surprisingly, there was no difference among the treatment groups in the amount of new bone.

Conclusion: The use of BMP-2 to augment impaction-grafted implants cannot be recommended even when combined with systemic zoledronate.

Keywords: allograft; arthroplasty; bisphosphonate; bone morphogenetic protein 2; implant fixation.

MeSH terms

  • Allografts
  • Animals
  • Bone Morphogenetic Protein 2* / administration & dosage
  • Bone Transplantation*
  • Bone and Bones / drug effects
  • Diphosphonates / administration & dosage
  • Dogs
  • Humans
  • Osseointegration / drug effects
  • Osteogenesis* / drug effects
  • Prostheses and Implants*
  • Prosthesis Design*
  • Random Allocation
  • Recombinant Proteins / administration & dosage
  • Titanium
  • Transforming Growth Factor beta* / administration & dosage
  • Transplantation, Homologous
  • Zoledronic Acid* / administration & dosage

Substances

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