Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion |
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Authors: | Ashish D Diwan Safdar N Khan Frank P Cammisa Jr Harvinder S Sandhu Joseph M Lane |
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Institution: | (1) Spinal Surgical Service, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, USA;(2) Department of Orthopaedic Surgery, University of California at Davis, Sacramento, CA, USA;(3) St George Hospital, University of New South Wales, Sydney, Australia; |
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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 μg 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. |
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Keywords: | Spinal fusion rhBMP-2 Nitric oxide Nitric oxide synthase |
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