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Using a murine model that features localized double inactivation of the <jats:italic>Nf1<\/jats:italic> gene in an experimental tibial fracture, we tested the effects of recombinant human bone morphogenetic protein\u20102 (rhBMP\u20102) and\/or the bisphosphonate zoledronic acid (ZA). Tibiae were harvested at 3 weeks for analysis, at which time there was negligible healing in un\u2010treated control fractures (7% union). In contrast, rhBMP\u20102 and rhBMP\u20102\/ZA groups showed significantly greater union (87% and 93%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01 for both). Treatment with rhBMP\u20102 led to a 12\u2010fold increase in callus bone volume and this was further increased in the rhBMP\u20102\/ZA group. Mechanical testing of the healed rhBMP\u20102 and rhBMP\u20102\/ZA fractures showed that the latter group had significantly higher mechanical strength and was restored to that of the un\u2010fractured contralateral leg. Co\u2010treatment with rhBMP\u20102\/ZA also reduced fibrous tissue infiltration at the fracture site compared to rhBMP alone (<jats:italic>p<\/jats:italic>\u2009=\u20090.068). These data support the future clinical investigation of this combination of anabolic and anti\u2010resorptive agents for the treatment of NF1 pseudarthrosis. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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