Non-Cochrane · intervention · PM35103837

Efficacy of nano-hydroxyapatite on caries prevention-a systematic review and meta-analysis.

Wierichs Richard Johannes, Wolf Thomas G, Campus Guglielmo, et al. · Clinical oral investigations · 2022 · PubMed · doi:10.1007/s00784-022-04390-4

Oral HealthDental cariesAMSTAR 2: Low / Critically Low (extractors disagree)
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
6
current version
GRADE rated
4
No studies
0
Included studies
10
linked below
No studies 0 · 0%Ungraded 2 · 33.3%Very low 4 · 66.7%Low 0 · 0%Moderate 0 · 0%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Review question

ElementPlanned (methods)Found (results)
PopulationPatients of any age with initial caries lesionsPatients with initial caries lesions in vivo (n=420 patients, 633 teeth, age 3-40) and enamel/dentin specimens in situ (n=1031 specimens in >95 patients)
InterventionFluoride-free (micro-/nano-)hydroxyapatite (nHA)Fluoride-free nHA dentifrice/paste (10 studies)
ComparisonAny other (placebo) treatment, or untreated/standard control (e.g., fluoride dentifrice)Fluoridated control (NaF) and nHA-free/fluoride-free (negative) control
OutcomesDevelopment of caries lesions (initiation and progression/regression): laser fluorescence, ICDAS score, enamel remineralization rate, mineral loss, lesion depthIn situ meta-analyses: mineral loss (transversal microradiography); in vivo (narrative): ICDAS score, laser fluorescence, photographic pixels, enamel acid resistance
Study designsRandomized controlled (in vivo and in situ) trials, prospective CCTs, prospective/retrospective cohort studies; split-mouth, parallel-arm or crossover designs10 studies: 5 in vivo RCTs + 5 crossover in situ studies
TimingMinimum follow-up 1 month (in vivo) / 14 days (in situ)In vivo median follow-up 6 months (range 6-12); in situ median 21 days (range 14-28)

Search date: Databases searched up to 30 April 2021 (CENTRAL up to 30 Apr 2021; MEDLINE/PubMed 1946 to 30 Apr 2021; Ovid EMBASE 1947 to 30 Apr 2021). Databases: Cochrane CENTRAL, MEDLINE (PubMed), Ovid EMBASE; grey literature: ClinicalTrials.gov, OpenGrey (opengrey.eu), National Research Register, ProQuest Dissertations & Theses

Questions and results

Fluoride-free nano-/micro-hydroxyapatite (nHA) dentifrice vs Fluoride-containing (fluoridated) dentifrice control

Population: Patients (children and adults, age 3-40 years) with initial enamel caries lesions (non-orthodontic and orthodontic)
1 question
OutcomeEffectEvidenceStatus / GRADE
Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)
Median follow-up 6 months (range 6-12 months)
No meta-analysis was possible for the 5 in vivo RCTs (high heterogeneity); narratively nHA showed generally no significant difference versus fluoridated dentifrice, and the evidence was not graded (ungraded).
Source: Results: In vivo studies (paras 1-2); Abstract; Table 1 (PICOS) · same question in other reviews
No meta-analysis was performed for the in vivo studies owing to high heterogeneity (population, control group, outcomes, follow-up periods, risk of bias) and differing statistical designs (e.g., non-inferiority);…5 studies · 420 participantsUngraded

Fluoride-free nano-hydroxyapatite (nHA) dentifrice/paste vs Fluoridated control (sodium fluoride, NaF)

Population: Enamel/dentin specimens with initial caries lesions (or sound surfaces) in intraoral (in situ) appliances worn by patients
2 questions
OutcomeEffectEvidenceStatus / GRADE
Mineral loss (transversal microradiography)
Median 21 days (range 14-28 days) · Net-demineralizing conditions
Under demineralizing conditions, nHA allowed significantly more enamel demineralization than NaF (MD 1625, 95% CI 553 to 2697; very low certainty).
Source: Results: In situ studies (para 2); Abstract; online supplementary Fig. 1 (not available) · same question in other reviews
MD 1625 [553, 2697]1 studyVery low
Downgraded: risk of bias
Mineral loss (transversal microradiography)
Median 21 days (range 14-28 days) · Net-remineralizing conditions
Under remineralizing conditions, nHA and NaF had the same remineralizing potential (MD -15, 95% CI -133 to 103; no significant difference; very low certainty).
Source: Results: In situ studies (para 2); Abstract · same question in other reviews
MD -15 [-133, 103]2 studiesVery low
Downgraded: risk of bias

Nano-hydroxyapatite (nHA) dentifrice/paste (fluoride-free or fluoridated) vs nHA-free / fluoride-free (negative) control

Population: Enamel/dentin specimens with initial caries lesions (or sound surfaces) in intraoral (in situ) appliances worn by patients
2 questions
OutcomeEffectEvidenceStatus / GRADE
Mineral loss (transversal microradiography)
Median 21 days (range 14-28 days) · Net-remineralizing conditions
Under remineralizing conditions, nHA produced significantly more remineralization than the negative control (MD 350, 95% CI 179 to 521; very low certainty).
Source: Results: In situ studies (para 2); Abstract · same question in other reviews
MD 350 [179, 521]1 studyVery low
Downgraded: risk of bias
Mineral loss (transversal microradiography)
Median 21 days (range 14-28 days) · Net-demineralizing conditions
Under demineralizing conditions, nHA did not differ from the fluoride-free control (MD -61, 95% CI -1301 to 1179; no significant difference; very low certainty).
Source: Results: In situ studies (para 2); Abstract · same question in other reviews
MD -61 [-1301, 1179]1 studyVery low
Downgraded: risk of bias

Comparison

1 question
OutcomeEffectEvidenceStatus / GRADE
Enamel acid resistance / initiation of new enamel caries lesions (in vivo, narrative)
nHA vs non-fluoridated comparator: nHA significantly superior [25] (Polyakova 2020)
no estimate extracted1 studyUngraded

AMSTAR 2 appraisal

Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.

ItemExtractor AExtractor BAgree
1Research question includes PICO componentsYesYesyes
2Protocol established before the reviewcriticalPartial YesPartial Yesyes
3Choice of study designs explainedNoYesno
4Comprehensive literature searchcriticalYesPartial Yesno
5Study selection in duplicateYesYesyes
6Data extraction in duplicateYesYesyes
7List of excluded studies with reasonscriticalYesNono
8Included studies described in detailYesNono
9Risk of bias assessed satisfactorilycriticalRCT: Yes · NRSI: N/ANRSI: N/A · RCT: Yesno
10Funding of included studies reportedYesNono
11Appropriate meta-analysis methodscriticalRCT: Yes · NRSI: N/ANRSI: N/A · RCT: Yesno
12Impact of risk of bias on the pooled resultsNoNoyes
13Risk of bias accounted for in interpretationcriticalYesYesyes
14Heterogeneity explainedYesNono
15Publication bias investigatedcriticalNoNoyes
16Conflicts of interest reportedYesYesyes
OverallLowCritically Lowno

Included primary studies 10

Open as a trial list
StudyAlso included byOutcomes it informs hereTrial PICOResults
Alhamed 2020
Effect of different remineralizing agents on the initial carious lesions - A comparative study.
PMID:33304082
this review onlyCaries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)not extracted yetnot extracted yet
Amaechi 2019
Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children.
PMID:31839988
this review onlyMineral loss (transversal microradiography)not extracted yetnot extracted yet
Badiee 2020
Comparison of the effects of toothpastes containing nanohydroxyapatite and fluoride on white spot lesions in orthodontic patients: A…
PMID:33343843
this review onlyCaries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)not extracted yetnot extracted yet
Najibfard 2011
Remineralization of early caries by a nano-hydroxyapatite dentifrice.
PMID:22403978
this review onlyMineral loss (transversal microradiography)not extracted yetnot extracted yet
Paszynska 2021
Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial.
PMID:33514787
this review onlyCaries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)not extracted yetnot extracted yet
Polyakova 2020
Qualitative and Quantitative Assessment of Remineralizing Effect of Prophylactic Toothpaste Promoting Brushite Formation: A Randomized…
PMID:32802784
this review onlyCaries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)not extracted yetnot extracted yet
Samuel 2016
Effect of ozone to remineralize initial enamel caries: in situ study.
PMID:26759338
this review onlynot statednot extracted yetnot extracted yet
Schlagenhauf 2019
Impact of a non-fluoridated microcrystalline hydroxyapatite dentifrice on enamel caries progression in highly caries-susceptible…
PMID:30701704
this review onlyCaries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance)not extracted yetnot extracted yet
Souza 2015
Effect of an Experimental Paste with Hydroxyapatite Nanoparticles and Fluoride on Dental Demineralisation and Remineralisation in situ.
PMID:26278685
this review onlynot statednot extracted yetnot extracted yet
Wierichs 2020
Re- and demineralization characteristics of dentin depending on fluoride application and baseline characteristics in situ.
PMID:32112909
this review onlynot statednot extracted yetnot extracted yet