Dose-Dependent Resorption of Allograft by rhBMP-2 Uncompensated by New Bone Formation-A Canine Study With Implants
Rasmus Cleemann1, Joan E Bechtold2, Mette Sorensen3
1Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark; Elective Surgery Center, Silkeborg Regional Hospital, Silkeborg, Denmark.
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.
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