Abstract
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/cm3) (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.
Keywords
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Article info
Publication history
Published online: April 19, 2023
Accepted:
April 11,
2023
Received in revised form:
March 6,
2023
Received:
December 5,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
FDA device/drug status: approved (Varenicline [Chantix]).
Author disclosures: BK: Nothing to disclose. HL: Nothing to disclose. GY: Nothing to disclose. ND: Nothing to disclose. JH: Nothing to disclose. ML: Nothing to disclose. JC: Nothing to disclose. AV: Royalties: Stryker (G), Globus (D), Medtronic (E), Atlas (D), Nuvasive (C), Alphatech Spine (B), Spine Wave (B), Edwards Lifescience Corporation (B). DM: Nothing to disclose. CK: Research support: Biomet, Medtronic, Regeneration Technologies.
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