Evaluation of zoledronate, cytochalasin-D, and desferrioxamine on osseointegration in an intra-medullary femoral implant model

OBJECTIVE: The rise in primary and revision surgeries utilizing joint replacement implants suggest the need for more reliable means of promoting implant fixation. Zoledronate-(Zol), cytochalasin-D-(cytoD), and desferrioxamine-(DFO) have been shown to enhance mesenchymal stem cell (MSC) differentiation into osteoblasts promoting bone formation. The objective was to determine whether Zol, cytoD, and DFO can improve fixation strength and enhance peri-implant bone volume about intra-medullary femoral implants. METHODS: 48 Sprague-Dawley female rats were randomized into four treatments, saline-control or experimental: Zol-(0.8 µg/µL), cytoD-(0.05 µg/µL), DFO-(0.4 µg/µL). Implants were placed bilaterally in the femoral canals following injection of treatment solution and followed for 28 days. Mechanical push-out testing and micro-CT were our primary evaluations, measuring load to failure and bone volume. Qualitative evaluation included histological assessment. Data was analyzed with a one-way ANOVA with Holm-Sidak mean comparison testing. RESULTS: Significant results included pushout tests showing an increase in maximum energy for Zol (124%) and cytoD (82%); Zol showed an increase in maximum load by 48%; Zol micro-CT showed increase in BV/TV by 35%. CONCLUSIONS: Our findings suggest that locally applied Zol and cytoD enhance implant mechanical stability. Bisphosphonates and actin regulators, like cytoD, might be further investigated as a new strategy for improving osseointegration.