Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint Infection

Background: Despite recent advances, infection remains the most common etiology of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D) deficiency correlates with the frequency of periprosthetic joint infection (PJI). We endeavored to examine whether 25D(3) deficiency leads to increased bacterial burden in vivo in an established mouse model of PJI and, if so, whether this effect can be reversed by preoperative 25D(3) supplementation. Methods: Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D-3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D(3)-deficientmice (n = 20) were "rescued" with 1 intraperitoneal dose of 25D(3) at 3 days before surgery. A stainless steel implant was inserted into the knee joint and the joint space was inoculated with bioluminescent Staphylococcus aureus (1 x 10(3) colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D(3) levels 3 days before surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21, and CFUs were quantified after culture. Myeloperoxidase (MPO) and beta-N-acetylglucos-aminidase (NAG) were assayed to look at neutrophil infiltration and activated tissue macrophage recruitment, respectively. Results: Serum values confirmed 25D(3) deficiency and repletion of the 25D(3)-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D(3)-deficient group. CFU counts from the joint tissue and implant were also significantly greater in this group (p < 0.05). Rescue treatment significantly decreased bacterial burden and neutrophil infiltration (p < 0.05). Compared with the 25D(3)-sufficient and 25D(3)-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D(3)-deficient group. Conclusions: This study demonstrated in vivo in a mouse model of PJI that (1) 25D(3) deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D(3).