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
\nfrustrating conditions encountered in pediatric orthopaedics
\nbecause of the difficulty in achieving healing.
\nNumerous treatment options have been explored with varying
\ndegrees of success1-19. Although some reports have demonstrated
\nsuccessful healing7,9,19, it is very difficult to restore the
\nnormal structural and functional integrity of the bone such as
\nthat which occurs after treatment of other types of fractures in
\nchildren. Advances in molecular biology have provided a better
\nunderstanding of the mechanisms of fracture-healing as well
\nas possible new solutions for the problem, including the use
\nof bone morphogenetic protein (BMP)20-24. In a controlled,
\nprospective, randomized study of 124 tibial nonunions (in
\n122 adult patients) treated with insertion of an intramedullary
\nrod and recombinant human (rh) BMP-7, no significant
\ndifference (p = 0.939) was noted between the BMP group
\nand the group that received an intramedullary rod and autogenous
\niliac crest bone grafts20. In a prospective, randomized,
\ncontrolled, single-blind study of 450 patients with an
\nopen tibial fracture, patients who were treated with rhBMP-
\n2 (1.50 mg/mL) had significantly (p = 0.005) superior results
\ncompared with patients who were treated with intramedullary
\nnail fixation and routine soft-tissue management as dictated
\nby the injury21. These two large clinical series suggest
\nthat BMPs may be a good alternative to autogenous iliaccrest
\nbone-grafting.
\nBone morphogenetic proteins have shown promising
\nresults in experimental animal models, and their clinical efficacy
\nhas been shown in the treatment of adult tibial nonunions
\nand in spinal fusion20-24. They have not been tested in
\nchildren because of uncertainty as to the effect on adjacent
\nphyses and because of concern about unexpected reactions.
\nThe use of BMP to treat congenital pseudarthrosis of the tibia
\nis a logical approach because the results from both animal
\nstudies and human trials have suggested that BMP is efficacious
\nin bone-healing. This prospective study was undertaken
\nto determine the clinical efficacy and safety of the use of
\nrhBMP-7 for the treatment of congenital pseudarthrosis of the
\ntibia in skeletally immature patients and to compare the results
\nwith those of previously published studies in which autogenous
\niliac-crest bone grafts have been used in conjunction
\nwith various fixation methods.