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Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion

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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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Acknowledgments

The authors would like to acknowledge Deirdre Campbell D.Eng, Russel Nord, BS, Micheal Peterkin, BS and Steven B. Doty, PhD for their invaluable assistance in the completion of this project.

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Authors and Affiliations

  1. Spinal Surgical Service, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, USA

    Ashish D. Diwan, Frank P. Cammisa Jr, Harvinder S. Sandhu & Joseph M. Lane

  2. Department of Orthopaedic Surgery, University of California at Davis, Sacramento, CA, USA

    Safdar N. Khan & Joseph M. Lane

  3. St George Hospital, University of New South Wales, Sydney, Australia

    Ashish D. Diwan & Joseph M. Lane

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  1. Ashish D. Diwan
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  2. Safdar N. Khan
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  3. Frank P. Cammisa Jr
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  4. Harvinder S. Sandhu
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  5. Joseph M. Lane
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Correspondence to Safdar N. Khan.

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Diwan, A.D., Khan, S.N., Cammisa, F.P. et al. Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion. Eur Spine J 19, 931–939 (2010). https://doi.org/10.1007/s00586-009-1263-7

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  • DOI: https://doi.org/10.1007/s00586-009-1263-7

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