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Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint
Vishal Hegde1, Erik M Dworsky, Alexandra I Stavrakis
11Department of Orthopaedic Surgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California.
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 25D3 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 25D3 supplementation.
Methods:
Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n = 20) were "rescued" with 1 intraperitoneal dose of 25D3 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 colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D3 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 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D3-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 25D3-sufficient and 25D3-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient group.
Conclusions:
This study demonstrated in vivo in a mouse model of PJI that (1) 25D3 deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D3.
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 25D3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.
Insights
Vitamin D3 deficiency increases bacterial burden and neutrophil infiltration in a mouse model of periprosthetic joint infection (PJI). Preoperative supplementation with vitamin D3 (25D3) reversed these effects, suggesting it may be a modifiable risk factor for PJI.
Area of Science:
- Orthopedics
- Infectious Disease
- Endocrinology
Background:
- Infection is a leading cause of arthroplasty failure.
- Low vitamin D (25-hydroxyvitamin D or 25D) levels correlate with periprosthetic joint infection (PJI) risk.
Purpose of the Study:
- To investigate if 25D deficiency increases bacterial burden in vivo in a mouse model of PJI.
- To determine if preoperative 25D3 supplementation can reverse this effect.
Main Methods:
- Mice received vitamin D3-sufficient or deficient diets for 6 weeks.
- A subset of deficient mice received 25D3 supplementation prior to surgical inoculation with Staphylococcus aureus.
- Bacterial burden, neutrophil infiltration, and inflammatory markers were assessed.
Main Results:
- 25D3 deficiency significantly increased bacterial load and neutrophil infiltration in PJI mouse models.
- Preoperative 25D3 repletion reversed these increases.
- Specific inflammatory markers (MPO, NAG) indicated altered immune cell activity.
Conclusions:
- 25D3 deficiency exacerbates bacterial burden and immune response in PJI.
- Vitamin D3 repletion is a potential strategy to mitigate PJI risk.
- 25D deficiency is a modifiable risk factor for PJI in arthroplasty patients.