Background: The role of bone morphogenetic proteins
(BMPs) in osseous repair has been demonstrated in numerous animal
models. Recombinant human osteogenic 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 Investigational Device
Exemption to establish both the safety and efficacy of this BMP in
the treatment of tibial nonunions. The study also compared the 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, partially 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 in 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 with 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 events were recorded, and sera were screened for antibodies
to OP-1 and type-I collagen at each outpatient visit.
Results: At 9 months following the operative procedures (the
primary end-point of this study), 81% of the OP-1-treated
nonunions (n = 63) and 85% of those receiving
autogenous bone (n = 61) were judged by clinical criteria
to have been treated successfully (p = 0.524). By radiographic
criteria, at this 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 observation,
and there was no statistically significant difference in outcome
between the two groups of patients at this point (p = 0.939).
All patients experienced 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 pain 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.