The influence of zoledronic acid and cyclophosphamide on microcirculation regeneration in healing oral mucosal flaps

Abstract

The use of intravenous nitrogenous bisphosphonates and antineoplastic agents as postoperative adjuvant cancer management strategies may influence the course of oral wound healing by altering tissue vascularisation kinetics. The aim of this study was to investigate if single or combined zoledronic acid (ZOL) and cyclophosphamide (CTX) would influence microcirculation regeneration in healing oral mucosal flaps. Twenty female specific-pathogen free New Zealand white rabbits were randomised into four groups. In all animals a mucosal flap was raised; three groups were treated each separately with intravenous infusions of 0.14mg/kg ZOL, 100mg/kg CTX, or both, respectively. The fourth group was used as a control. Capillary density measurements, expressed as the mean number of capillaries±SD per mm2 (cpll/mm2), was performed preoperatively using sidestream dark-field (SDF) imaging and repeated immediately postoperatively and on days 2, 4, 7, 9, 11, 14, and 21. Whole blood count and body weight was assessed in each group to monitor pharmacotherapeutic responses. Preoperative mean capillary density was 74±8cpll/mm2 and 40±11cpll/mm2 directly after surgery (P<0.0001). Post hoc comparisons of follow-up SDF measurements on days 9–21 between control and ZOL vs. CTX and ZOL+CTX were statistically significant (P<0.05). The present study demonstrates that ZOL did not alter capillary regeneration in healing mucosal flaps. However, although the early healing phase is generally characterised by rapid progression of capillary regeneration, interventions with CTX and ZOL+CTX significantly altered capillary regeneration and persisted beyond the third postoperative week.