School of Podiatric Medicine Medical Student Research
Document Type
Poster
Publication Date
Fall 2024
Abstract
Introduction Zoledronate (Zol) is a nitrogenous bisphosphonate (nBP) used to treat osteoporosis, bone metastases, and Charcot foot. Despite its efficacy in preventing fractures, concerns exist about its side effects on mesenchyme-origin cells and impaired wound healing. We hypothesize that Zol may impair the responses of human fibroblasts (hF) and pre-osteoblasts (MC3T3), potentially compromising tissue healing in the lower extremities of patients with diabetes.
Methodology: MC3T3 cells and hF were cultured in 96-well plates at a density of 2.5 x 10³ cells for 48 and 72 hours, respectively. Cells were subjected to normal glucose, high glucose, and high oxidative stress conditions (0.2 mM to 0.4 mM H₂O₂) and exposed to various Zol concentrations (0.1 to 100 µM). Viability was assessed using a tetrazolium compound assay with absorbance at 490 nm. Quantitative data were analyzed using One-Way ANOVA followed by Tukey's test, with a significance level set at 0.05%.
Results: Zol treatment reduced hF and MC3T3 viability significantly from concentrations of 1 and 5 µM upwards, respectively. It also lowered hF viability in normal and high glucose environments, reducing to as low as 11% under 0.2 mM H₂O₂ across all conditions. No significant changes were observed in MC3T3 cell proliferation under high glucose conditions.
Conclusion: Our preliminary findings suggest that Zol may impair the viability and proliferation of mesenchymal-derived cells, potentially affecting wound healing, particularly in diabetic conditions. Additional studies are needed to explore these effects further and at lower dosages of H₂O₂in these cells as they are exposed to nBPs.
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