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Maximizing bone formation in posterior spine fusion using rhBMP‐2 and zoledronic acid in wild type and NF1 deficient mice

Spinal pseudarthrosis is a well described complication of spine fusion surgery in NF1 patients. Reduced bone formation and excessive resorption have been described in NF1 and anti‐resorptive agents may be advantageous in these individuals. In this study, 16 wild type and 16 Nf1+/− mice were subjected to posterolateral fusion using collagen sponges containing 5 µg rhBMP‐2 introduced bilaterally. Mice were dosed twice weekly with 0.02 mg/kg zoledronic acid (ZA) or sterile saline. The fusion mass was assessed for bone volume (BV) and bone mineral density (BMD) by microCT. Co‐treatment using rhBMP‐2 and ZA produced a significant increase (p < 0.01) in BV of the fusion mass compared to rhBMP‐2 alone in both wild type mice (+229%) and Nf1+/− mice (+174%). Co‐treatment also produced a significantly higher total BMD of the fusion mass compared to rhBMP‐2 alone in both groups (p < 0.01). Despite these gains with anti‐resorptive treatment, Nf1+/− deficient mice still generated less bone than wild type controls. TRAP staining on histological sections indicated an increased osteoclast surface/bone surface (Oc.S/BS) in Nf1+/− mice relative to wild type mice, and this was reduced with ZA treatment. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1090–1094, 2014.