Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions - A prospective, randomized clinical trial comparing rhOP-1 with fresh bone autograft

Background: The role of bone morphogenetic proteins (BMPs) in osseous repai r has been demonstrated in numerous animal models. Recombinant human osteog enic protein-1 (rhOP-1 or BMP-7) has now been produced and was evaluated in a clinical trial conducted under a Food and Drug Administration approved I nvestigational Device Exemption to establish both the safety and efficacy o f this BMP in the treatment of tibial nonunions. The study also compared th e clinical and radiographic results with this osteogenic molecule and those achieved with fresh autogenous bone. Materials and Methods: One hundred and twenty-two patients (with 124 tibial nonunions) were enrolled in a controlled, prospective, randomized, partial ly blinded, multi-center clinical trial between February, 1992, and August, 1996, and were followed at frequent intervals over 24 months. Each patient was treated by insertion of an intramedullary rod, accompanied by rhOP-1 i n a type I collagen carrier or by fresh bone autograft. Assessment criteria included the severity of pain at the fracture site, the ability to walk wi th full weight-bearing, the need for surgical re-treatment of the nonunion during the course of this study, plain radiographic evaluation of healing, and physician satisfaction with the clinical course. In addition, adverse e vents were recorded, and sera were screened for antibodies to OP-l and type -1 collagen at each outpatient visit. Results: At 9 months following the operative procedures (the primary end-po int of this study), 81% of the OP-1-treated nonunions (n = 63) and 85% of t hose receiving autogenous bone (n = 61) were judged by clinical criteria to have been treated successfully (p = 0.524). By radiographic criteria, at t his same time point, 75% of those in the OP-1-treated group and 84% of the autograft-treated patients had healed fractures (p = 0.218). These clinical results continued at similar levels of success throughout 2 years of obser vation, and there was no statistically significant difference in outcome be tween the two groups of patients at this point (p = 0.939). All patients ex perienced adverse events. Forty-four percent of patients in each treatment group had serious events, none of which were related to their bone grafts. More than 20% of patients treated with autografts had chronic donor site pa in following the procedure. Conclusions: rhOP-1 (BMP-7), implanted with a type I collagen carrier, was a safe and effective treatment for tibial nonunions. This molecule provided clinical and radiographic results comparable with those achieved with bone autograft, without donor site morbidity.