Non-Cochrane · intervention · PM41825436

Effects of Antibiotics and Anti-Inflammatory Drugs on Enamel Development: A Systematic Review with Quantitative Synthesis.

Zamri Nadia, Ngo Hien, Court Elizabeth, et al. · International dental journal · 2026 · PubMed · doi:10.1016/j.identj.2026.109478

Findings

3 findings

Population
Developing enamel in experimental animals (rats, mice)Amoxicillin, amoxicillin plus clavulanate, or amoxicillin plus NaFNo medication (control)Enamel thickness
Exposure during enamel development
SMD (Cohen's d) 0.79 [0.40, 1.36]
GRADE not reported
5 studies
Developing enamel in experimental animals (mice)Antibiotics (amoxicillin, amoxicillin plus clavulanate, erythromycin) and anti-inflammatory drugs (celecoxib, indomethacin, ibuprofen, acetaminophen)No medication (control)Enamel phosphorus content
Exposure during enamel development
SMD (Cohen's d) 0.46 [-0.31, 1.75]
GRADE not reported
4 studies
Developing enamel in experimental animals (mice)Antibiotics (amoxicillin, amoxicillin plus clavulanate, erythromycin) and anti-inflammatory drugs (celecoxib, indomethacin, ibuprofen, acetaminophen)No medication (control)Enamel calcium content
Exposure during enamel development
SMD (Cohen's d) 0.52 [-0.21, 1.46]
GRADE not reported
4 studies

Included primary studies 12

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Abe 2003
Effects of a Macrolide Antibiotic on Enamel Formation in Rat Incisors-Primary Lesion of Ameloblast at the Transition Stage
DOI:10.1292/jvms.65.985
2003this review onlynot statednot extracted yet
de Souza 2016
Amoxicillin diminishes the thickness of the enamel matrix that is deposited during the secretory stage in rats
DOI:10.1111/ipd.12184
2015this review onlyEnamel thicknessnot extracted yet
Feltrin-Souza 2021
In vivo effect of fluoride combined with amoxicillin on enamel development in rats
DOI:10.1590/1678-7757-2021-0171
2021this review onlyEnamel thicknessnot extracted yet
Gao 2020
Effects of applying amoxicillin in juvenile mice on enamel mineralization and the expression of kallikrein‑related peptidase 4 and tight…
PMID:32626909
2020this review onlyEnamel calcium content; Enamel phosphorus contentnot extracted yet
Goncalves 2022
Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
DOI:10.1038/s41598-022-19583-w
2022this review onlyEnamel calcium content; Enamel phosphorus contentnot extracted yet
Gottberg 2014
Prenatal effects by exposing to amoxicillin on dental enamel in Wistar rats.
PMID:24121904
2014this review onlynot statednot extracted yet
Kameli 2019
Effects of Amoxicillin on the Structure and Mineralization of Dental Enamel and Dentin in Wistar Rats
DOI:10.18502/fid.v16i2.1364
2019this review onlyEnamel thicknessnot extracted yet
Mihalas 2016
The Role of Chronic Exposure to Amoxicillin/Clavulanic Acid on the Developmental Enamel Defects in Mice
DOI:10.1177/0192623315610822
2015this review onlyEnamel calcium content; Enamel phosphorus contentnot extracted yet
Sabah 2023
Evaluation of the Effects of Amoxicillin on Tooth Development in Rats by Histological and Histomorphometric Study
DOI:10.32592/ari.2023.78.4.1333
2022this review onlyEnamel thicknessnot extracted yet
Sahlberg 2013
Combined effect of amoxicillin and sodium fluoride on the structure of developing mouse enamel in vitro
DOI:10.1016/j.archoralbio.2013.03.007
2013this review onlyEnamel thicknessnot extracted yet
Schmalfuss 2022
Effects of antibiotics on the developing enamel in neonatal mice
DOI:10.1007/s40368-021-00677-4
2021this review onlynot statednot extracted yet
Serna Munoz 2018
Effect of antibiotics and NSAIDs on cyclooxygenase-2 in the enamel mineralization
DOI:10.1038/s41598-018-22607-z
2018this review onlyEnamel calcium content; Enamel phosphorus contentnot extracted yet

Review question

ElementPlanned (methods)Found (results)
PopulationDeveloping enamel (animal and in vitro models)Rats and mice; tooth germ culture (n=12 studies)
InterventionNSAIDs, acetaminophen, amoxicillin, amoxicillin+clavulanate, ampicillin, gentamicin, macrolides, tetracycline, azithromycin, alone or with fluorideAmoxicillin, amoxicillin+clavulanate, ampicillin, gentamicin, erythromycin, macrolide, tetracycline, celecoxib, indomethacin, ibuprofen, acetaminophen, NaF
ComparisonNo medicationUntreated or saline control
OutcomesAmeloblast morphology; enamel matrix proteins and enzymes; enamel mineralization (Ca, P); enamel thicknessEnamel thickness (5 studies); Ca and P (4 studies); qualitative ameloblast and matrix outcomes
Study designsIn vitro and in vivo experimental studies12 experimental studies (in vivo animal and one in vitro)
TimingNot specifiedNot specified