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

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 treat...

Full description

Saved in:
Bibliographic Details
Main Authors: Aysan Lektemur Alpan, Alper Kızıldağ, Özlem Özmen, Necati Zavrak, Zeynep Özdoğan, Aysun Akpınar
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Oral Health
Subjects:
Online Access:https://doi.org/10.1186/s12903-025-06254-1
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849238212935942144
author Aysan Lektemur Alpan
Alper Kızıldağ
Özlem Özmen
Necati Zavrak
Zeynep Özdoğan
Aysun Akpınar
author_facet Aysan Lektemur Alpan
Alper Kızıldağ
Özlem Özmen
Necati Zavrak
Zeynep Özdoğan
Aysun Akpınar
author_sort Aysan Lektemur Alpan
collection DOAJ
description 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.
format Article
id doaj-art-362235b7e2d9492b8d1da130f1b49d12
institution Kabale University
issn 1472-6831
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series BMC Oral Health
spelling doaj-art-362235b7e2d9492b8d1da130f1b49d122025-08-20T04:01:42ZengBMCBMC Oral Health1472-68312025-07-0125111310.1186/s12903-025-06254-1The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat modelAysan Lektemur Alpan0Alper Kızıldağ1Özlem Özmen2Necati Zavrak3Zeynep Özdoğan4Aysun Akpınar5Department of Periodontology, Faculty of Dentistry, Pamukkale UniversityDepartment of Periodontology, Faculty of Dentistry, Pamukkale UniversityDepartment of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy UniversityDepartment of Periodontology, Faculty of Dentistry, Pamukkale UniversityDepartment of Periodontology, Faculty of Dentistry, Pamukkale UniversityDepartment of Periodontology, Faculty of Dentistry, Bursa Uludağ UniversityAbstract 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.https://doi.org/10.1186/s12903-025-06254-1Alveolar bone graftingMetronidazolemicro-CTImmunohistochemistryRatsXenograft
spellingShingle Aysan Lektemur Alpan
Alper Kızıldağ
Özlem Özmen
Necati Zavrak
Zeynep Özdoğan
Aysun Akpınar
The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
BMC Oral Health
Alveolar bone grafting
Metronidazole
micro-CT
Immunohistochemistry
Rats
Xenograft
title The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
title_full The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
title_fullStr The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
title_full_unstemmed The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
title_short The effects of local and systemic metronidazole on bone healing in mandibular defects: a rat model
title_sort effects of local and systemic metronidazole on bone healing in mandibular defects a rat model
topic Alveolar bone grafting
Metronidazole
micro-CT
Immunohistochemistry
Rats
Xenograft
url https://doi.org/10.1186/s12903-025-06254-1
work_keys_str_mv AT aysanlektemuralpan theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT alperkızıldag theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT ozlemozmen theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT necatizavrak theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT zeynepozdogan theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT aysunakpınar theeffectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT aysanlektemuralpan effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT alperkızıldag effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT ozlemozmen effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT necatizavrak effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT zeynepozdogan effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel
AT aysunakpınar effectsoflocalandsystemicmetronidazoleonbonehealinginmandibulardefectsaratmodel