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

Abstract

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