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 -deficient mice (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 × 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 β-N-acetylglucosaminidase (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 . Clinical Relevance: Considering that >65% of patients undergoing arthroplasty have insufficient or low levels of total 25D and that 25D levels can be replenished with ease using a U.S. Food and Drug Administration (FDA)-approved, oral 25D 3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.