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

摘要

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.