Friday, September 28, 2018 4:05 PM–5:05 PM abstracts: basic science of spinal fusion: 233. Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model

Abstract

BACKGROUND CONTEXT Opioid use is prevalent for management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in-vitro, and one previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. PURPOSE To study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. STUDY DESIGN/SETTING Preclinical animal study. PATIENT SAMPLE A total of 24 adult New Zealand white rabbits. OUTCOME MEASURES Assessment of fusion was done by manual palpation, plain radiographs, micro-computed tomography (microCT), and histology. METHODS A total of 24 adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received four-weeks preoperative and six-weeks postoperative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and four-weeks postoperatively to ensure adequate levels. The control group (n=12) received only perioperative pain control as necessary. All animals received a bilateral L5-L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the six-week postoperative time point for analysis. RESULTS A total of 12 animals in control group and 11 animals in the opioid group were available for analysis at the end of six weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=.09), lower trabecular number (p=.02) and higher trabecular separation (p=.02) as compared to control. Histological analysis found areas of incorporation of autograft, and unincorporated graft fragments in both groups. In the control group, there was remodeling of de-novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de-novo woven bone, and hypertrophied osteoblasts seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histological findings of relatively immature fusion mass in the opioid group. CONCLUSIONS Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at six-weeks in this rabbit spinal fusion model. These preliminary results lay foundation for further research to investigate underlying cellular mechanisms, temporal fusion process, and dose-duration relationship of opioids responsible for our findings.