Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Metformin | Research

Combination of metformin and double antibiotic paste for the regeneration of non-vital immature teeth: a preliminary randomized clinical study

Authors: Fereshte Sobhnamayan, Safoora Sahebi, Fariborz Moazami, Parastoo Malekzadeh, Soheila Hasani

Published in: BMC Oral Health | Issue 1/2023

Login to get access

Abstract

Background

The present study aimed to investigate whether incorporating metformin in double antibiotic paste (DAP) can promote the regeneration process of non-vital immature teeth.

Methods

Out of 32 pediatric patients undergoing regenerative endodontic procedures (REPs), 6 cases with a follow-up period of less than 12 months or lack of documentation were excluded then the remaining 26 were analyzed. 15 cases received DAP, and 11 cases received a DAP + metformin as the intra-canal medicament, kept for an average of 23 days. During 18 months of follow-up, clinical and radiographic examinations were performed to evaluate the treatment outcomes based on the resolution of apical periodontitis, root development, and the occurrence of intracanal calcification. The chi-square test was used for the statistical analysis (P < 0.05).

Results

All patients demonstrated resolution of apical periodontitis; however, complete apical closure was only seen in 50% of the patients. The rate of apical closure and root length was significantly higher in the DAP + metformin group (P = 0.047), although the two groups were not significantly different in terms of root width (P = 0.184). Canal obliteration was seen in 15% of cases, all of which were in the DAP group.

Conclusions

According to the present findings, metformin could promote root development in the regeneration process when incorporated in DAP.

Trial registration

This clinical trial was registered on the Iranian Registry of Clinical Trials (IRCT20200120046197N1) on 26.2.2021.
Literature
1.
Silujjai J, Linsuwanont P. Treatment outcomes of apexification or revascularization in nonvital immature permanent teeth: a retrospective study. J Endod. 2017;43(2):238–45.PubMedCrossRef
2.
Felippe W, Felippe M, Rocha M. The effect of mineral trioxide aggregate on the apexification and periapical healing of teeth with incomplete root formation. Int Endod J. 2006;39(1):2–9.PubMedCrossRef
3.
4.
Jeeruphan T, Jantarat J, Yanpiset K, Suwannapan L, Khewsawai P, Hargreaves KM. Mahidol study 1: comparison of radiographic and survival outcomes of immature teeth treated with either regenerative endodontic or apexification methods: a retrospective study. J Endod. 2012;38(10):1330–6.PubMedCrossRef
5.
Saoud TMA, Zaazou A, Nabil A, Moussa S, Lin LM, Gibbs JL. Clinical and radiographic outcomes of traumatized immature permanent necrotic teeth after revascularization/revitalization therapy. J Endod. 2014;40(12):1946–52.PubMedPubMedCentralCrossRef
6.
Jadhav G, Shah N, Logani A. Revascularization with and without platelet-rich plasma in nonvital, immature, anterior teeth: a pilot clinical study. J Endod. 2012;38(12):1581–7.PubMedCrossRef
7.
Sabrah AH, Yassen GH, Spolnik KJ, Hara AT, Platt JA, Gregory RL. Evaluation of residual antibacterial effect of human radicular dentin treated with triple and double antibiotic pastes. J Endod. 2015;41(7):1081–4.PubMedCrossRef
8.
Qin W, Chen J-Y, Guo J, Ma T, Weir MD, Guo D, et al. Novel calcium phosphate cement with metformin-loaded chitosan for odontogenic differentiation of human dental pulp cells. Stem Cells Int. 2018;2018:1–11.CrossRef
9.
Gathani KM, Raghavendra SS. Scaffolds in regenerative endodontics: a review. Dent Res J (Isfahan). 2016;13(5):379–86.PubMedCrossRef
10.
Nosrat A, Kolahdouzan A, Khatibi AH, Verma P, Jamshidi D, Nevins AJ, Torabinejad M. Clinical, radiographic, and histologic outcome of regenerative endodontic treatment in human teeth using a novel collagen-hydroxyapatite scaffold. J Endod. 2019;45(2):136–43.PubMedCrossRef
11.
Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: a review of current status and a call for action. J Endod. 2007;33(4):377–90.PubMedCrossRef
12.
Zhu X, Zhang C, Huang GT-J, Cheung GS, Dissanayaka WL, Zhu W. Transplantation of dental pulp stem cells and platelet-rich plasma for pulp regeneration. J Endod. 2012;38(12):1604–9.PubMedCrossRef
13.
Hargreaves KM, Giesler T, Henry M, Wang Y. Regeneration potential of the young permanent tooth: what does the future hold? J Endod. 2008;34(7):51–S6.CrossRef
14.
Viollet B, Guigas B, Garcia NS, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci. 2011;122(6):253–70.CrossRef
15.
Jang WG, Kim EJ, Bae I-H, Lee K-N, Kim YD, Kim D-K, et al. Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2. Bone. 2011;48(4):885–93.PubMedCrossRef
16.
Gao Y, Xue J, Li X, Jia Y, Hu J. Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells. J Pharm Pharmacol. 2008;60(12):1695–700.PubMedCrossRef
17.
Cortizo AM, Sedlinsky C, McCarthy AD, Blanco A, Schurman L. Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture. Euro J Pharmacol. 2006;536(1–2):38–46.CrossRef
18.
Molinuevo MS, Schurman L, McCarthy AD, Cortizo AM, Tolosa MJ, Gangoiti MV, et al. Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies. J Bone Mineral Res. 2010;25(2):211–21.CrossRef
19.
Wang S, Xia Y, Ma T, Weir MD, Ren K, Reynolds MA, et al. Novel metformin-containing resin promotes odontogenic differentiation and mineral synthesis of dental pulp stem cells. Drug Deliv Transl Res. 2019;9(1):85–96.PubMedPubMedCentralCrossRef
20.
Pradeep AR, Patnaik K, Nagpal K, Karvekar S, Ramamurthy BL, Naik SB, et al. Efficacy of locally-delivered 1% metformin gel in the treatment of intrabony defects in patients with chronic periodontitis: a randomized, controlled clinical trial. J Invest Clin Dent. 2016;7(3):239–45.CrossRef
21.
Sharma P, Grover HS, Masamatti SS, Saksena N. A clinicoradiographic assessment of 1% metformin gel with platelet-rich fibrin in the treatment of mandibular grade II furcation defects. J Indian Soc Periodontol. 2017;21(4):303–8.PubMedPubMedCentral
22.
ElSheshtawy A, Nazzal H, El Shahawy O, El Baz A, Ismail S, Kang J, Ezzat K. The effect of platelet-rich plasma as a scaffold in regeneration/revitalization endodontics of immature permanent teeth assessed using 2‐dimensional radiographs and cone beam computed tomography: a randomized controlled trial. Int Endod J. 2020;53(7):905–21.PubMedCrossRef
23.
Youssef A, Ali M, ElBolok A, Hassan R. Regenerative endodontic procedures for the treatment of necrotic mature teeth: a preliminary randomized clinical trial. Int Endod J. 2022;55(4):334–46.PubMedCrossRef
24.
Bose R, Nummikoski P, Hargreaves K. A retrospective evaluation of radiographic outcomes in immature teeth with necrotic root canal systems treated with regenerative endodontic procedures. J Endod. 2009;35(10):1343–9.PubMedCrossRef
25.
Cehreli ZC, Isbitiren B, Sara S, Erbas G. Regenerative endodontic treatment (revascularization) of immature necrotic molars medicated with calcium hydroxide: a case series. J Endod. 2011;37(9):1327–30.PubMedCrossRef
26.
Song M, Cao Y, Shin S-J, Shon W-J, Chugal N, Kim RH, et al. Revascularization-associated intracanal calcification: assessment of prevalence and contributing factors. J Endod. 2017;43(12):2025–33.PubMedCrossRef
27.
Chen MH, Chen KL, Chen CA, Tayebaty F, Rosenberg P, Lin L. Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures. Int Endod J. 2012;45(3):294–305.PubMedCrossRef
28.
Petrino JA, Boda KK, Shambarger S, Bowles WR, McClanahan SB. Challenges in regenerative endodontics: a case series. J Endod. 2010;36(3):536–41.PubMedCrossRef
29.
Ding RY, Cheung GS-p, Chen J, Yin XZ, Wang QQ, Zhang CF. Pulp revascularization of immature teeth with apical periodontitis: a clinical study. J Endod. 2009;35(5):745–9.PubMedCrossRef
30.
Palma PJ, Martins J, Diogo P, Sequeira D, Ramos JC, Diogenes A, Santos JM. Does apical papilla survive and develop in apical periodontitis presence after regenerative endodontic procedures? Appl Sci. 2019;9(19):3942.CrossRef
31.
Lin J, Zeng Q, Wei X, Zhao W, Cui M, Gu J, et al. Regenerative endodontics versus apexification in immature permanent teeth with apical periodontitis: a prospective randomized controlled study. J Endod. 2017;43(11):1821–7.PubMedCrossRef
32.
Meschi N, Palma PJ, Cabanillas‐Balsera D. Effectiveness of revitalization in treating apical periodontitis: A systematic review and meta‐analysis. Int Endod J. 2023;56:510–32.
33.
Jiang X, Liu H, Peng C. Continued root development of immature permanent teeth after regenerative endodontics with or without a collagen membrane: a randomized, controlled clinical trial. Int J Pediatr Dent. 2022;32(2):284–93.CrossRef
34.
Chueh L-H, Ho Y-C, Kuo T-C, Lai W-H, Chen Y-HM. Chiang C-P. Regenerative endodontic treatment for necrotic immature permanent teeth. J Endod. 2009;35(2):160–4.PubMedCrossRef
35.
Thibodeau B, Teixeira F, Yamauchi M, Caplan DJ, Trope M. Pulp revascularization of immature dog teeth with apical periodontitis. J Endod. 2007;33(6):680–9.PubMedCrossRef
36.
Wang X, Thibodeau B, Trope M, Lin LM, Huang GT-J. Histologic characterization of regenerated tissues in canal space after the revitalization/revascularization procedure of immature dog teeth with apical periodontitis. J Endod. 2010;36(1):56–63.PubMedCrossRef
37.
Yamauchi N, Yamauchi S, Nagaoka H, Duggan D, Zhong S, Lee SM, et al. Tissue engineering strategies for immature teeth with apical periodontitis. J Endod. 2011;37(3):390–7.PubMedCrossRef
38.
da Silva LAB, Nelson-Filho P, da Silva RAB, Flores DSH, Heilborn C, Johnson JD, Cohenca N. Revascularization and periapical repair after endodontic treatment using apical negative pressure irrigation versus conventional irrigation plus triantibiotic intracanal dressing in dogs’ teeth with apical periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(5):779–87.PubMedCrossRef
39.
Pradeep A, Nagpal K, Karvekar S, Patnaik K, Naik SB, Guruprasad C. Platelet-rich fibrin with 1% metformin for the treatment of intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2015;86(6):729–37.PubMedCrossRef
40.
Qin W, Gao X, Ma T, Weir MD, Zou J, Song B, et al. Metformin enhances the differentiation of dental pulp cells into odontoblasts by activating AMPK signaling. J Endod. 2018;44(4):576–84.PubMedPubMedCentralCrossRef
41.
Griss T, Vincent EE, Egnatchik R, Chen J, Ma EH, Faubert B, et al. Metformin antagonizes cancer cell proliferation by suppressing mitochondrial-dependent biosynthesis. PLoS Biol. 2015;13(12):e1002309.PubMedPubMedCentralCrossRef
42.
Lai EH-H, Yang C-N, Lin S-K, Wang H-W, Kok S-H, Hong C-Y, et al. Metformin ameliorates periapical lesions through suppression of hypoxia-induced apoptosis of osteoblasts. J Endod. 2018;44(12):1817–25.PubMedCrossRef
43.
Liu L, Zhang C, Hu Y, Peng B. Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin. J Endod. 2012;38(7):943–7.PubMedCrossRef
44.
Pradeep A, Rao NS, Naik SB, Kumari M. Efficacy of varying concentrations of subgingivally delivered metformin in the treatment of chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2013;84(2):212–20.PubMedCrossRef
Metadata
Title
Combination of metformin and double antibiotic paste for the regeneration of non-vital immature teeth: a preliminary randomized clinical study
Authors
Fereshte Sobhnamayan
Safoora Sahebi
Fariborz Moazami
Parastoo Malekzadeh
Soheila Hasani
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03591-x

Other articles of this Issue 1/2023

BMC Oral Health 1/2023 Go to the issue

Research

High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients

Research

In vitro performance of an autocured universal adhesive system in bonding to dentin

Research

Dental pulp cells cocultured with macrophages aggravate the inflammatory conditions stimulated by LPS

Research

Temporomandibular disorder severity and its association with psychosocial and sociodemographic factors in Turkish adults

Research

Oral microbial communities in 5-year-old children with versus without dental caries

Research

Association between retinol intake and periodontal health in US adults