RHBMP2 AND PAMIDRONATE IN EXPERIMENTAL ALLOGRAFTED GAP IMPLANTS – CATASTROPHIC RESULTS

Abstract

Introduction: Bone grafts should be biocompatible, mechanically stable and be replaced with new bone over time. BMP’s are known to increase bone formation around allografted implants, but have also been associated with increased graft resorption and implant instability. Bone resorption can be inhibited by bisphosphonates.

We hypothesized that topical bisphosphonate (Pamidronate, Mayne Pharma) in combination with rhBMP2 (InductOs, Wyeth) would give increased mechanical implant fixation and increased new bone formation without excessive allograft resorption. We looked at both porous-coated Ti implants and HA-coated implants.

Methods: Four 2.5 mm gap implants were inserted into the proximal humeri of each of 16 dogs. The gap around each implant was filled with fresh frozen impacted allograft with or without intervention treatment. Half the dogs received Ti-implants, the other half HA-implants. The 4 treatment groups were:

1. allograft alone (control)

2. allograft + rhBMP2

3. allograft + pamidronate

4. allograft + rhBMP2 + pamidronate (combination)

The observation time was 4 weeks.

Results: For both the Ti and HA subgroup, the control-group had significantly better mechanical fixation than all other groups by push-out test. The fixation was twofold higher in the control group than the rhBMP2-group and more than 20-fold higher than the pamidronate group and combined group. The HA implants were twice as well fixed as the Ti implants with corresponding treatment.

The HA implants had less fibrous tissue and more new bone compared to the Ti implants. The fractions of allograft were the same.

The rhBMP2 group had more new bone and much less fibrous tissue than the mechanically superior control group. However, there was almost no allograft left in the rhBMP2 group due to extreme resorption.

The addition of pamidronate seemed to freeze bone metabolism around the implants. Neither in the pamidronate group nor in the combination group was there anything but minor new bone growth. The allograft was preserved. In the pamidronate group there was a dense, thick fibrous capsule around the implants. This was not the case in the combined rhBMP2-pamidronate group, and is most likely a positive effect of the rhBMP2.

Discussion: Topical pamidronate and rhBMP2 in combination and alone greatly weakened the mechanical fixation of the implants. The experiment confirms previous reports of mechanical instability of implants when BMPs are added to periimplanteric defects. Pamidronate alone had catastrophic effects on bone metabolism and implant fixation in this experiment.

The negative results with rhBMP2 may be due to over dosage, which warrants further preclinical testing. Despite the limitations of this animal study with non-loaded implants, the results encourage extreme caution in adjuvant therapies of arthroplastic surgery.