title: Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion.
abstract: A novel rat model was used to investigate the effect of nitric oxide synthase inhibition in posterior spinal fusion augmented with recombinant human bone morphogenetic protein-2. Nitric oxide (NO) has important physiological functions including the modulation of fracture healing. Recombinant human BMP-2 (rhBMP-2) enhances spinal fusion. It is not known whether nitric oxide has a role in rhBMP-2 enhanced spinal fusion and remodeling. A novel rat intertransverse fusion model was created using a defined volume of bone graft along with a collagen sponge carrier, which was compacted and delivered using a custom jig. The control groups consisted of a sham group (S, n = 20), an autograft + carrier group (A, n = 28) and a group consisting of 43 microg of rhBMP-2 mixed with autograft + carrier (AB, n = 28). Two experimental groups received a nitric oxide synthase (NOS) inhibitor, N (G)-nitro L-arginine methyl ester, in a dose of 1 mg/ml ad lib in the drinking water (AL, n = 28) and one of these experimental groups had rhBMP-2 added to the graft mixture at the time of surgery (ALB, n = 28). Rats were killed at 22 and 44 days, spinal columns subjected to radiology, biomechanics and histology. On a radiographic score (0-4) indicating progressive maturation of bone fusion mass, no difference was found between the A and AL groups, however, there was a significant enhancement of fusion when rhBMP-2 was added when compared to the A group (P < 0.001). However, on day 44, the ALB group showed significantly less fusion progression when compared to the AB group (P < 0.01). There was a 25% (P < 0.05) more fusion-mass-area in day 44 of ALB group when compared to day 44 of the AB group indicating that NOS inhibition delayed the remodeling of the fusion mass. Biomechanically, the rhBMP-2 groups were stiffer at all time points compared to the NOS inhibited groups. Decalcified histology demonstrated that there was a delay in graft incorporation whenever NOS was inhibited (AL and ALB groups) as assessed by a 5 point histological maturation score. In a novel model of rat intertransverse process fusion, nitric oxide synthase modulates rhBMP-2 induced corticocancellous autograft incorporation.
authors.affiliation: Spinal Surgical Service, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, USA.
authors.forename: Ashish D
authors.initials: AD
authors.lastname: Diwan
authors.forename: Safdar N
authors.initials: SN
authors.lastname: Khan
authors.forename: Frank P
authors.initials: FP
authors.lastname: Cammisa
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Sandhu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lane
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D016025:Bone Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000502:physiology* / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods*; D014182:Transplantation, Autologous / Q000379:methods*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011993:Recombinant Fusion Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase