Varenicline mitigates the increased risk of pseudarthrosis associated with nicotine.

Autor: Karamian BA; Rothman Orthopaedic Institute, 925 Chestnut, 5th Floor, Philadelphia, PA, 19107, USA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA; Department of Orthopaedic Surgery, University of Utah, Salt Lake City, UT, USA. Electronic address: bkspinemd@gmail.com., Levy HA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA; Department of Orthopaedic Surgery, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA., Yalla GR; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., D'Antonio ND; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Heard JC; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Lambrechts MJ; Rothman Orthopaedic Institute, 925 Chestnut, 5th Floor, Philadelphia, PA, 19107, USA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Canseco JA; Rothman Orthopaedic Institute, 925 Chestnut, 5th Floor, Philadelphia, PA, 19107, USA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Vaccaro AR; Rothman Orthopaedic Institute, 925 Chestnut, 5th Floor, Philadelphia, PA, 19107, USA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Markova DZ; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA., Kepler CK; Rothman Orthopaedic Institute, 925 Chestnut, 5th Floor, Philadelphia, PA, 19107, USA; Department of Orthopaedic Surgery, Thomas Jefferson University, 1025 Walnut St #100, Philadelphia, PA 19107, USA.
Jazyk: angličtina
Zdroj: The spine journal : official journal of the North American Spine Society [Spine J] 2023 Aug; Vol. 23 (8), pp. 1212-1222. Date of Electronic Publication: 2023 Apr 20.
DOI: 10.1016/j.spinee.2023.04.005
Abstrakt: Background Context: High serum nicotine levels increase the risk of nonunion after spinal fusion. Varenicline, a pharmaceutical adjunct for smoking cessation, is a partial agonist designed to displace and outcompete nicotine at its receptor binding site, thereby limiting downstream activation. Given its mechanism, varenicline may have therapeutic benefits in mitigating nonunion for active smokers undergoing spinal fusion.
Purpose: To compare fusion rate and fusion mass characteristics between cohorts receiving nicotine, varenicline, or concurrent nicotine and varenicline after lumbar fusion.
Study Design: Rodent noninstrumented spinal fusion model.
Methods: Sixty eight-week-old male Sprague-Dawley rats weighing approximately 300 grams underwent L4-5 posterolateral fusion (PLF) surgery. Four experimental groups (control: C, nicotine: N, varenicline: V, and combined: NV [nicotine and varenicline]) were included for analysis. Treatment groups received nicotine, varenicline, or a combination of nicotine and varenicline delivered through subcutaneous osmotic pumps beginning two weeks before surgery until the time of sacrifice at age 14 weeks. Manual palpation testing, microCT imaging, bone histomorphometry, and biomechanical testing were performed on harvested spinal fusion segments.
Results: Control (p=0.016) and combined (p=0.032) groups, when compared directly to the nicotine group, demonstrated significantly greater manual palpation scores. The fusion rate in the control (93.3%) and combined (93.3%) groups were significantly greater than that of the nicotine group (33.3%) (p=0.007, both). Biomechanical testing demonstrated greater Young's modulus of the fusion segment in the control (17.1 MPa) and combined groups (34.5 MPa) compared to the nicotine group (8.07 MPa) (p<0.001, both). MicroCT analysis demonstrated greater bone volume fraction (C:0.35 vs N:0.26 vs NV:0.33) (p<0.001, all) and bone mineral density (C:335 vs N:262 vs NV:328 mg Ha/cm 3 ) (p<0.001, all) in the control and combined groups compared to the nicotine group. Histomorphometry demonstrated a greater mineral apposition rate in the combined group compared to the nicotine group (0.34 vs 0.24 μm/day, p=0.025).
Conclusion: In a rodent spinal fusion model, varenicline mitigates the adverse effects of high nicotine serum levels on the rate and quality of spinal fusion.
Clinical Significance: These findings have the potential to significantly impact clinical practice guidelines and the use of pharmacotherapy for active nicotine users undergoing fusion surgery.
Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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