Modulation of spine fusion with BMP-2, MEK inhibitor (PD0325901), and zoledronic acid in a murine model of NF1 double inactivation

Background Spine fusion is a common procedure for the treatment of severe scoliosis, a frequent and challenging deformity associated with Neurofibromatosis type 1 (NF1). Moreover, deficiencies in NF1-Ras-MEK signaling affect bone formation and resorption that in turn impacts on spine fusion outcomes. Methods In this study we describe a new model for AdCre virus induction of Nf1 deficiency in the spines of Nf1flox/flox mice. The virus is delivered locally to the mouse spine in a fusion procedure induced using BMP-2. Systemic adjunctive treatment with the MEK inhibitor (MEKi) PD0325901 and the bisphosphonate zoledronic acid (ZA) were next trialed in this model. Results AdCre delivery resulted in abundant fibrous tissue (Nf1null +393%, P Conclusions These data not only support the utility of an AdCre-virus induced knockout spine model, but also support further investigation of MEKi and ZA as adjunctive therapies for improving BMP-2 induced spine fusion in the context of NF1.