104. Effects of cannabinoids on spinal fusion in a rat model

Abstract

<h3>BACKGROUND CONTEXT</h3> The opioid epidemic is a public health crisis causing significant morbidity, mortality and economic costs nationwide. As a result, discovering alternative forms of pain management is becoming imperative. Medical marijuana is an option for a nonopioid analgesic and is under investigation for potential uses in fields such as oncology and chronic pain, but it is yet to be studied in the surgical setting. Specifically, its effects on bone healing are not fully understood, significantly affecting its potential analgesic efficacy for postorthopaedic surgical care. <h3>PURPOSE</h3> The goal of this this study is to determine the effect of cannabis derivatives, D9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on bone healing. The effects of marijuana on spinal arthrodesis specifically have yet to be investigated. We hypothesized that THC and CBD will not decrease bone healing in a rat model for spinal fusion. <h3>STUDY DESIGN/SETTING</h3> A basic science study utilizing a validated experimental model to assess spinal fusion performed on rats. <h3>PATIENT SAMPLE</h3> N/A (Sprague-Dawley rats were used for this basic science study). <h3>OUTCOME MEASURES</h3> Manual palpation was done to assess strength of the L4-L5 arthrodesis on all rats. Twelve rats underwent lumbar three-dimensional micro-computed tomography (μCT) imaging and histological analysis. The remaining half were subjected to quantitative polymerase chain reaction (qPCR) analyses which are currently pending. The μCT bone analysis was comprised of quantifying the ratio of bone volume (BV) to total volume (TV) within each volume of interest (VOI), as well as bone mineral density (BMD) and tissue mineral density (TMD) for the corresponding VOI. During follow-up, one animal from the saline and one from the combination group were lost due to wound dehiscence. Kruskal-Wallis test followed by Dunn's multiple comparisons test was performed using GraphPad Prism. Two-tailed values of p < 0.05 were considered statistically significant. <h3>METHODS</h3> Animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC). Twenty-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone graft (4 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed under surgical microscopy. The animals were divided into four groups of 6, each receiving 0.1ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5 mg/kg CBD (combo). Eight weeks postsurgery, animals were euthanized and fusions were assessed. <h3>RESULTS</h3> The combination treatment group had the highest fusion rates, with 66.7% demonstrating full fusion and 33.3% demonstrating partial fusion. This was followed by the THC group demonstrating 60% of rats with full fusion, 20% with partial fusion, and 20% with no fusion. Fusion rates were lower in the CBD and saline groups. However, the fusion rates were not significantly different between the treatment groups based on our manual palpation scoring. Callus formation was visually more extensive in THC and Combo treatments on μCT 3D reconstruction images. This observation was confirmed though μCT data, in which bone volume fraction (BV/TV) was significantly higher for the CBD and THC treatment groups compared to the saline treatment group (P <0.05). BMD and TMD values were higher for all cannabis treatment groups compared to the saline treatment group, though not statistically significant. <h3>CONCLUSIONS</h3> This study preliminarily demonstrates that CBD and THC have no adverse effect on bone regeneration and rate of spinal fusion in rats. Cannabinoids may possess osteoinductive properties which require further investigation. Future larger animal studies should further investigate the effects of cannabinoid receptor agonists on bone healing and formation, with additional exploration of cannabinoid receptor agonists as a potential alternative approach to postoperative analgesia following spinal fusion and other procedures requiring bone formation. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.