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.
The Centre for Children's Bone Health, Sydney Children's Hospital Network, Sydney, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
Justin
J
Bobyn
Anton
A
Rasch
Mikulec
M
Kathy
David G
DG
Little
Aaron
A
Schindeler
D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D009456:Neurofibromatosis 1 / Q000601:surgery; D025542:Neurofibromin 1 / Q000235:genetics*; D010012:Osteogenesis; D011542:Pseudarthrosis / Q000188:drug therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D013123:Spinal Fusion / Q000009:adverse effects*; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D007093:Imidazoles; D025542:Neurofibromin 1; D011994:Recombinant Proteins; D000077211:Zoledronic Acid
NF1; neurofibromatosis; scoliosis; spine fusion