Impact of perioperative buprenorphine administration on bacterial burden and infection-related osteolysis in a preclinical model of orthopaedic-device related infection

Purpose To investigate, in an established rodent model, whether administration of an opioid (buprenorphine) increases the risk of developing an orthopaedic-device related infection (ODRI), and whether prolonged buprenorphine administration interferes with treatment outcome for established ODRI. The primary outcome was infection status; secondary outcomes included bone morphology and implant osseointegration assessed by quantitative microCT. Methods The study comprised two arms. In the “risk study”, 20 rats received proximal tibia implants inoculated with 10 2 CFU of Staphylococcus epidermidis ; 10 were treated with buprenorphine (0,1 mg/kg s.c., once daily for five days), and 10 received saline. Animals were euthanized on day 9. MicroCT scans were performed at surgery and euthanasia. Quantitative bacteriology of bone, soft tissues, and implants was performed post-mortem. In the “interference study”, 24 rats received implants inoculated with 106 CFU of S. epidermidis; 12 were treated with buprenorphine (0,1mg/kg s.c., day 7-18) and 12 received saline. Two buprenorphine-treated animals were excluded because of a deviation from the administration protocol. All animals received cefazolin and rifampin from day 7-21. Longitudinal MicroCT scans were acquired on day 0, 9, 20, and 28. Animals were euthanized on day 28. Three animals per group underwent histopathology; the remainder were assessed by bacteriology. Results Bacteriological analyses in both arms showed no significant differences between control and treated groups in infection burden or bacterial clearance. In the interference study, persistent infection occurred in 3/12 control animals versus 7/10 buprenorphine-treated animals (p = 0.0836). An exploratory comparison between the two study arms revealed reduced bone formation under high versus moderate contamination (p = 0.0056). No statistically significant effect of buprenorphine on bone morphology was detected under high contamination, whereas under moderate contamination buprenorphine was associated with reduced bone formation. Conclusions No statistically significant increase in ODRI risk or antibiotic treatment response was detected in the buprenorphine-treated group. A non-significant trend toward higher infection persistence in buprenorphine-treated animals warrants further investigations. High bacterial load reduced bone formation, while buprenorphine did not impair short-term osseointegration or infection-related bone remodeling.