The effects of varenicline on lumbar spinal fusion in a rat model.

Abstract

BACKGROUND CONTEXT:

Smoking is detrimental to obtaining a solid spinal fusion mass with previous studies demonstrating its association with pseudoarthrosis in patients undergoing spinal fusion. Varenicline is a pharmacologic adjunct used in smoking cessation which acts as a partial agonist of the same nicotinic receptors activated during tobacco use. However, no clinical or basic science studies to date have characterized if varenicline has negative effects on spinal fusion and bone healing by itself.

PURPOSE:

Our study's aim was to elucidate whether varenicline affects the frequency or quality of posterolateral spinal fusion in a rodent model at an endpoint of 12 weeks.

STUDY DESIGN:

Randomized control trial.

PATIENT SAMPLE:

Fourteen male Lewis rats randomly separated into two experimental groups.

OUTCOME MEASURES:

Manual palpation of fusion segment, radiography, μCT imaging, and four-point bend.

METHODS:

Fourteen male Lewis rats were randomly separated into two experimental groups undergoing L4-L5 posterior spinal fusion procedure followed by daily subcutaneous injections of human dose varenicline or saline (control) for 12 weeks postsurgery. Spine samples were explanted, and fusion was determined via manual palpation of segments by two independent observers. High-resolution radiographs were obtained to evaluate bridging fusion mass. μCT imaging was performed to characterize fusion mass and consolidation. Lumbar spinal fusion units were tested in four-point bending to evaluate stiffness and peak load. Study funding sources include $5000 OREF Grant. There were no applicable financial relationships or conflicts of interest.

RESULTS:

At 3 months postsurgery, 12 out of 14 rats demonstrated lumbar spine fusion (86% fused) with no difference in fusion frequency between the varenicline and control groups as detected by manual palpation. High-resolution radiography revealed six out of seven rats (86%) having complete fusion in both groups. μCT showed no significant difference in bone mineral density or bone fraction volume between groups in the region of interest. Biomechanical testing demonstrated no significant different in the average stiffness or peak loads at the fusion site of the varenicline and control groups.

CONCLUSION:

Based on the results of our rat study, there is no indication that varenicline itself has a detrimental effect on the frequency and quality of spinal fusion.

• Authors: Jason R Kang, Juliane D Glaeser, Brian Karamian, Linda Kanim, Zachary NaPier, Jayme Koltsov, Timothy Thio, Khosrowdad Salehi, Hyun W Bae, Ivan Cheng
• Journal: The spine journal : official journal of the North American Spine Society (Spine J) Vol. 20 Issue 2 Pg. 300-306 (02 2020) ISSN: 1878-1632 [Electronic] United States
• PMID: 31377475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Smoking Cessation Agents
• Varenicline

Topics

• Animals
• Bone Regeneration (drug effects)
• Lumbar Vertebrae (surgery)
• Male
• Postoperative Complications (etiology)
• Random Allocation
• Rats
• Rats, Inbred Lew
• Smoking Cessation Agents (adverse effects)
• Spinal Fusion (adverse effects)
• Varenicline (adverse effects)