Effect of local melatonin application on immediately placed implants in maxillary premolars (a biochemical and...

Melatonin, a potent antioxidant and bone-regulating hormone, promotes osteoblastic activity and inhibits osteoclastic differentiation primarily through upregulation of osteoprotegerin (OPG) and suppression of the receptor activator of nuclear factor-kappa B ligand (RANKL) pathway. Given its dual osteogenic and antiresorptive effects, melatonin may enhance bone remodelling around immediately placed implants. This study aimed to evaluate the effect of locally applied melatonin on peri-implant bone remodelling by assessing changes in OPG levels and radiographic bone parameters over time.

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

Biochemical findings: At one month, OPG levels were significantly higher in the melatonin group compared to the control group (p = 0.012). By 3 months, there was no statistically significant difference between the two groups (p = 0.707). Radiographic findings: After six months, relative bone density was numerically higher in the melatonin group than in the control group, although the between-group difference was not statistically significant (p = 0.372). However, the percentage increase from baseline was significantly greater in the melatonin group (p = 0.002). Bone volume decreased in both groups, with a percent reduction in bone volume that was significantly smaller in the melatonin group compared to the control group (p < 0.001). Marginal bone loss was significantly lower in the melatonin group compared to the control group (p < 0.001).

Locally applied melatonin was associated with favourable early biochemical and radiographic outcomes, including a greater percentage increase in relative bone density from baseline, preservation of peri-implant bone volume, and reduced marginal bone loss.

The trial was retrospectively registered at the Clinicaltrials.gov registry (Registration ID #NCT07103564), first submitted on July 29, 2025 https://clinicaltrials.gov/study/NCT07103564 .