The Effects of Local and Systemic Metronidazole on Bone Healing in Mandibular Defects: a Rat Model

Abstract

ObjectiveThis study evaluated the effects of local and systemic Metronidazole (MTZ) on bone healing in infected mandibular defects using a rat model.Study designThirty Wistar rats were divided into Control, Local MTZ (L-MTZ), and Systemic MTZ (S-MTZ) groups. Mandibular defects were treated with xenograft mixed saliva from periodontitis patients. Bone regeneration was evaluated using micro-CT and histological analyses. Bone morphogenic protein-2 (BMP-2), alkaline phosphatase (ALP), receptor activator of nuclear factor kappaB ligand (RANKL), osteocalcin (OCN), and beta-catenin (beta-catenin), high sensitivity C-reactive protein (hs-CRP) levels evaluated.ResultsIncreased bone formation and reduced osteoclast counts were detected in the L-MTZ group compared to the Control. beta-catenin expression was significantly higher in the L-MTZ group, BMP-2 and Runx2 levels were elevated in both L-MTZ and S-MTZ groups. ALP and OCN levels were the highest in the L-MTZ group, with no significant difference between the L-MTZ and S-MTZ groups. hs-CRP levels were significantly lower in MTZ-treated groups. Micro-CT analysis revealed the highest bone volume/total volume (BV/TV) ratio in the S-MTZ group among all groups.ConclusionLocal MTZ application enhanced bone regeneration by promoting osteoblast activity, activating beta-catenin and BMP-2/Runx2 signaling, and reducing inflammation. Systemic MTZ also improved bone healing, particularly in volumetric aspects.