Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1. +/−. ) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1. +/−. mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1

Congenital pseudarthrosis of the tibia (CPT) is a rare but well recognised condition. Obtaining union of the pseudarthrosis in these children is often difficult and may require several surgical procedures. The treatment has changed significantly since the review by Hardinge in 1972, but controversies continue as to the best form of surgical treatment. This paper reviews these controversies.

Cite this article: Bone Joint J 2013;95-B:1027–34.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of congenital pseudarthrosis of the tibia has been investigated in only one previous study, with promising results. The aim of this study was to determine whether rhBMP-2 might improve the outcome of this disorder. We reviewed the medical records of five patients with a mean age of 7.4 years (2.3 to 21) with congenital pseudarthrosis of the tibia who had been treated with rhBMP-2 and intramedullary rodding. Ilizarov external fixation was also used in four of these patients. Radiological union of the pseudarthrosis was evident in all of them at a mean of 3.5 months (3.2 to 4) post-operatively. The Ilizarov device was removed after a mean of 4.2 months (3.0 to 5.3). These results indicate that treatment of congenital pseudarthrosis of the tibia using rhBMP-2 in combination with intramedullary stabilisation and Ilizarov external fixation may improve the initial rate of union and reduce the time to union.

Further studies with more patients and longer follow-up are necessary to determine whether this surgial procedure may significantly enhance the outcome of congenital pseudarthrosis of the tibia, considering the refracture rate (two of five patients) in this small case series.