Treatment of congenital pseudarthrosis of the tibia with recombinant human bone morphogenetic protein-7 (rhBMP-7). A report of five cases

Abstract

Congenital pseudarthrosis of the tibia is one of the most frustrating conditions encountered in pediatric orthopaedics because of the difficulty in achieving healing. Numerous treatment options have been explored with varying degrees of success1-19. Although some reports have demonstrated successful healing7,9,19, it is very difficult to restore the normal structural and functional integrity of the bone such as that which occurs after treatment of other types of fractures in children. Advances in molecular biology have provided a better understanding of the mechanisms of fracture-healing as well as possible new solutions for the problem, including the use of bone morphogenetic protein (BMP)20-24. In a controlled, prospective, randomized study of 124 tibial nonunions (in 122 adult patients) treated with insertion of an intramedullary rod and recombinant human (rh) BMP-7, no significant difference (p = 0.939) was noted between the BMP group and the group that received an intramedullary rod and autogenous iliac crest bone grafts20. In a prospective, randomized, controlled, single-blind study of 450 patients with an open tibial fracture, patients who were treated with rhBMP- 2 (1.50 mg/mL) had significantly (p = 0.005) superior results compared with patients who were treated with intramedullary nail fixation and routine soft-tissue management as dictated by the injury21. These two large clinical series suggest that BMPs may be a good alternative to autogenous iliaccrest bone-grafting. Bone morphogenetic proteins have shown promising results in experimental animal models, and their clinical efficacy has been shown in the treatment of adult tibial nonunions and in spinal fusion20-24. They have not been tested in children because of uncertainty as to the effect on adjacent physes and because of concern about unexpected reactions. The use of BMP to treat congenital pseudarthrosis of the tibia is a logical approach because the results from both animal studies and human trials have suggested that BMP is efficacious in bone-healing. This prospective study was undertaken to determine the clinical efficacy and safety of the use of rhBMP-7 for the treatment of congenital pseudarthrosis of the tibia in skeletally immature patients and to compare the results with those of previously published studies in which autogenous iliac-crest bone grafts have been used in conjunction with various fixation methods.