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
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
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients of any age with initial caries lesions | Patients 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) |
| Intervention | Fluoride-free (micro-/nano-)hydroxyapatite (nHA) | Fluoride-free nHA dentifrice/paste (10 studies) |
| Comparison | Any other (placebo) treatment, or untreated/standard control (e.g., fluoride dentifrice) | Fluoridated control (NaF) and nHA-free/fluoride-free (negative) control |
| Outcomes | Development of caries lesions (initiation and progression/regression): laser fluorescence, ICDAS score, enamel remineralization rate, mineral loss, lesion depth | In situ meta-analyses: mineral loss (transversal microradiography); in vivo (narrative): ICDAS score, laser fluorescence, photographic pixels, enamel acid resistance |
| Study designs | Randomized controlled (in vivo and in situ) trials, prospective CCTs, prospective/retrospective cohort studies; split-mouth, parallel-arm or crossover designs | 10 studies: 5 in vivo RCTs + 5 crossover in situ studies |
| Timing | Minimum 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
| Outcome | Effect | Evidence | Status / 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 participants | Ungraded |
Fluoride-free nano-hydroxyapatite (nHA) dentifrice/paste vs Fluoridated control (sodium fluoride, NaF)
| Outcome | Effect | Evidence | Status / 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 study | Very 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 studies | Very low Downgraded: risk of bias |
Nano-hydroxyapatite (nHA) dentifrice/paste (fluoride-free or fluoridated) vs nHA-free / fluoride-free (negative) control
| Outcome | Effect | Evidence | Status / 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 study | Very 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 study | Very low Downgraded: risk of bias |
Comparison
| Outcome | Effect | Evidence | Status / 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 extracted | 1 study | Ungraded |
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.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | Yes | no |
| 4Comprehensive literature searchcritical | Yes | Partial Yes | no |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | Yes | No | no |
| 8Included studies described in detail | Yes | No | no |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | Yes | No | no |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | No | no |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Low | Critically Low | no |
Included primary studies 10
Open as a trial list| Study | Also included by | Outcomes it informs here | Trial PICO | Results |
|---|---|---|---|---|
| Alhamed 2020 Effect of different remineralizing agents on the initial carious lesions - A comparative study. PMID:33304082 | this review only | Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance) | not extracted yet | not 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 only | Mineral loss (transversal microradiography) | not extracted yet | not 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 only | Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance) | not extracted yet | not extracted yet |
| Najibfard 2011 Remineralization of early caries by a nano-hydroxyapatite dentifrice. PMID:22403978 | this review only | Mineral loss (transversal microradiography) | not extracted yet | not 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 only | Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance) | not extracted yet | not extracted yet |
| Polyakova 2020 Qualitative and Quantitative Assessment of Remineralizing Effect of Prophylactic Toothpaste Promoting Brushite Formation: A Randomized… PMID:32802784 | this review only | Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance) | not extracted yet | not extracted yet |
| Samuel 2016 Effect of ozone to remineralize initial enamel caries: in situ study. PMID:26759338 | this review only | not stated | not extracted yet | not extracted yet |
| Schlagenhauf 2019 Impact of a non-fluoridated microcrystalline hydroxyapatite dentifrice on enamel caries progression in highly caries-susceptible… PMID:30701704 | this review only | Caries lesion initiation/progression (ICDAS score, laser fluorescence/DIAGNOdent, photographic pixels, enamel acid resistance) | not extracted yet | not 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 only | not stated | not extracted yet | not extracted yet |
| Wierichs 2020 Re- and demineralization characteristics of dentin depending on fluoride application and baseline characteristics in situ. PMID:32112909 | this review only | not stated | not extracted yet | not extracted yet |