The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model


Alpan A. L., Kızıldağ A., Özmen Ö., Zavrak N., Özdoğan Z., AKPINAR A.

BMC Oral Health, vol.25, no.1, 2025 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1186/s12903-025-06254-1
  • Journal Name: BMC Oral Health
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: Alveolar bone grafting, Immunohistochemistry, Metronidazole, micro-CT, Rats, Xenograft
  • Bursa Uludag University Affiliated: Yes

Abstract

Objective: This study evaluated the effects of local and systemic Metronidazole (MTZ) on bone healing in infected mandibular defects using a rat model. Study design: Thirty 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 (β-catenin), high sensitivity C-reactive protein (hs-CRP) levels evaluated. Results: Increased bone formation and reduced osteoclast counts were detected in the L-MTZ group compared to the Control. β-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. Conclusion: Local MTZ application enhanced bone regeneration by promoting osteoblast activity, activating β-catenin and BMP-2/Runx2 signaling, and reducing inflammation. Systemic MTZ also improved bone healing, particularly in volumetric aspects.