Individual clinical trials are valuable. But in evidence-based medicine, the systematic review and meta-analysis sits at the top of the evidence hierarchy — it pools data across multiple independent studies to test whether findings are consistent, and calculates a combined statistical estimate that no single trial can produce on its own.

In December 2024, Pawinska, Paszynska, Amaechi, Meyer, Enax, and Limeback published exactly that in the Journal of Dentistry, an updated systematic review and meta-analysis of all available clinical evidence on hydroxyapatite in oral care products and dental caries. ^[1]

It is, to date, the most comprehensive synthesis of the evidence base on this ingredient.

What is a meta-analysis?

A meta-analysis mathematically combines data from multiple independent studies to produce a single, statistically robust estimate of an effect. Because it draws on larger combined sample sizes and accounts for variation between studies, it provides stronger evidence than any individual trial. It sits at the top of the clinical evidence hierarchy, above randomised controlled trials.

The review searched PubMed, Scopus, EMBASE, and Web of Science for all clinical studies where participants of any age used hydroxyapatite-containing oral care products, toothpastes, mouthwashes, or gels and where outcomes included a direct or proxy measure of caries reduction or remineralisation. ^[1] The search covered all publications up to 31 December 2023.

After applying inclusion and exclusion criteria which deliberately excluded studies combining HAP with fluoride, to isolate HAP's independent effect, 18 studies were retrieved and assessed. Of those, 13 were included in the meta-analysis: 5 clinical trials (in vivo) and 8 in situ studies. ^[1]

The meta-analysis produced four separate quantitative results — one for clinical trial caries prevention, one for in situ remineralisation, one for in situ lesion depth, and one for bacterial load reduction. Each tells a distinct part of the story.^[1]

On caries prevention: the pooled clinical trial data showed HAP toothpaste produced a 2.51 times higher chance of preventing dental caries compared to a placebo toothpaste — a statistically significant result. ^[1] When compared directly to fluoride toothpaste, the odds ratio was 1.1 in favour of HAP — slightly better, though not statistically superior. The authors note this is consistent with non-inferiority findings across all three individual RCTs included.

"The clinical studies show that the chance to prevent dental caries is 2.51 higher when using a HAP toothpaste compared to a placebo toothpaste. When comparing HAP toothpaste to a fluoride toothpaste, the OR is 1.1 for HAP to prevent dental caries, which is slightly better than fluoride."

— Pawinska et al., Journal of Dentistry, 2024

On remineralisation: in situ studies showed a weighted mean difference of 2.8% mineral gain in favour of HAP over fluoride — a positive trend, though not reaching statistical significance across the pooled data. ^[1] On lesion depth: the weighted mean difference was 1.15 µm reduction in favour of HAP — and this result was statistically significant. ^[1]

On bacterial load: the most striking result came from the in situ biofilm studies. HAP mouthrinse produced a mean 65% reduction in bacterial load compared to the negative control — a statistically significant finding. ^[1] Importantly, the studies showed HAP achieved this through an anti-adherence mechanism rather than killing bacteria, meaning beneficial oral flora is preserved — a meaningful distinction from chlorhexidine and antimicrobial agents.

One of the strengths of this meta-analysis is that it draws together evidence across three distinct but complementary mechanisms by which HAP reduces caries risk:^[1]

The review also confirms that HAP adheres not only to enamel but to titanium, ceramics, and polymer surfaces — relevant for anyone with dental implants or restorations, and for any future application in clinical settings.^[1]

A notable feature of this review is the breadth of populations covered. The five clinical trials included in the meta-analysis span preschool children (aged 3–6), school-age children, adolescents undergoing orthodontic treatment, and healthy adults aged 18–45. The authors state directly: ^[1]

"As a sole active ingredient, considered safe if swallowed, hydroxyapatite is an ideal substitute for fluoride in toothpaste and mouthwash tailored for young children, and new data as presented in this review, demonstrated that hydroxyapatite-based oral care products can be used by people of all ages."

— Pawinska et al., Journal of Dentistry, 2024

The review also notes that among all non-fluoride anti-caries agents studied — including tricalcium phosphate, amorphous calcium phosphate, casein phosphopeptide-stabilised ACP, bioactive glass, and others — HAP has the highest structural similarity to natural enamel, and has been the most extensively studied with the most consistent efficacy evidence. ^[1]