Effect of local melatonin application on immediately placed implants in maxillary premolars (a biochemical and radiographic randomized controlled clinical trial).

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title: "Local Melatonin Application Around Immediately Placed Dental Implants: What a Small RCT Found"

description: "A randomized controlled trial in 24 patients examined whether locally applied melatonin influences bone remodelling around immediately placed maxillary premolar implants."

date: "2025"

evidenceTier: "C"

studyType: "Randomized controlled trial"

journal: "BMC Oral Health"

pubmedId: "42892692"

TL;DR

In a small randomized trial of 24 patients, locally applied Melatonin around immediately placed dental implants was associated with higher early OPG levels, less marginal bone loss, and less bone volume reduction at six months than implants placed without it . The study is small, single-centre, and short, so these findings are preliminary.

What the study found

Melatonin has been studied for its antioxidant properties and for its effects on bone cells. Laboratory and animal work suggests it can favour osteoblast (bone-forming cell) activity and suppress osteoclast (bone-resorbing cell) differentiation, partly by raising osteoprotegerin (OPG) and dampening the RANKL pathway. The authors built on this rationale by asking whether melatonin placed locally at a dental implant site could influence bone remodelling in humans.

The trial enrolled 24 patients with non-restorable maxillary premolars, divided into two groups. The melatonin group received immediately placed implants with local melatonin application, while the control group received immediately placed implants without it. Serum OPG was measured at one and three months, and cone-beam computed tomography (CBCT) was performed immediately after placement and at six months to assess relative bone density, bone volume, and marginal bone loss.

On the biochemical side, OPG levels were significantly higher in the melatonin group at one month (p = 0.012), but the difference had disappeared by three months (p = 0.707). This pattern suggests a transient early signal rather than a sustained change in OPG over the study period.

The radiographic results were more mixed in their presentation. At six months, relative bone density was numerically higher in the melatonin group, but this between-group difference was not statistically significant (p = 0.372). The percentage increase from baseline, however, was significantly greater in the melatonin group (p = 0.002). Bone volume fell in both groups, but the percentage reduction was significantly smaller with melatonin (p < 0.001). Marginal bone loss was also significantly lower in the melatonin group (p < 0.001).

Taken together, the trial reports favourable early biochemical and radiographic outcomes with local melatonin. Several caveats matter for interpretation. The sample was small, the follow-up was six months, the sample size calculation is not reported in the summary, and the trial was retrospectively registered. The between-group bone density difference was not significant, and the OPG effect did not persist to three months. These points temper how strongly the results should be read.

What this means for you

If you are considering dental implants: This study does not establish that melatonin improves implant outcomes in routine practice. Discuss the approach with your dentist or oral surgeon, and ask about the evidence behind any adjunct they propose.

Systemic melatonin supplements are a different question: This trial studied local application at the implant site, not oral supplementation. Do not extrapolate these findings to Melatonin taken as a pill for bone health.

Bone health more broadly: Established factors for bone maintenance include Resistance training and adequate Protein at every meal. These are supported by a much larger body of evidence than this single trial.

Await replication: Larger, longer, and independently replicated trials are needed before clinical recommendations can change.

Study details

Item	Detail
Study type	Randomized controlled trial (biochemical and radiographic)
Population	24 patients with non-restorable maxillary premolars
Groups	Immediate implant with local melatonin vs. immediate implant without melatonin
Outcomes	Serum OPG (1 and 3 months); CBCT bone density, bone volume, marginal bone loss (baseline and 6 months)
Key findings	Higher OPG at 1 month (p = 0.012), not at 3 months; greater bone density increase from baseline (p = 0.002); smaller bone volume reduction (p < 0.001); less marginal bone loss (p < 0.001)
Limitations	Small sample, short follow-up, single-centre, retrospective registration, between-group bone density difference not significant
Registration	ClinicalTrials.gov NCT07103564
Journal	BMC Oral Health
Evidence tier	C

Sources

1. Effect of local melatonin application on immediately placed implants in maxillary premolars (a biochemical and radiographic randomized controlled clinical trial). *BMC Oral Health*. PubMed. https://pubmed.ncbi.nlm.nih.gov/42892692/

2. ClinicalTrials.gov. NCT07103564. https://clinicaltrials.gov/study/NCT07103564

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ProtocolEngine provides general health information based on published research. This is not medical advice. Consult a healthcare professional before starting any supplement or health protocol.