Improved union and bone strength in a mouse model of NF1 pseudarthrosis treated with recombinant human bone morphogenetic protein‐2 and zoledronic acid

Tibial pseudarthrosis associated with Neurofibromatosis type 1 (NF1) is an orthopedic condition with consistently poor clinical outcomes. Using a murine model that features localized double inactivation of the Nf1 gene in an experimental tibial fracture, we tested the effects of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and/or the bisphosphonate zoledronic acid (ZA). Tibiae were harvested at 3 weeks for analysis, at which time there was negligible healing in un‐treated control fractures (7% union). In contrast, rhBMP‐2 and rhBMP‐2/ZA groups showed significantly greater union (87% and 93%, p  < 0.01 for both). Treatment with rhBMP‐2 led to a 12‐fold increase in callus bone volume and this was further increased in the rhBMP‐2/ZA group. Mechanical testing of the healed rhBMP‐2 and rhBMP‐2/ZA fractures showed that the latter group had significantly higher mechanical strength and was restored to that of the un‐fractured contralateral leg. Co‐treatment with rhBMP‐2/ZA also reduced fibrous tissue infiltration at the fracture site compared to rhBMP alone ( p  = 0.068). These data support the future clinical investigation of this combination of anabolic and anti‐resorptive agents for the treatment of NF1 pseudarthrosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:930–936, 2018.