Topical silver diamine fluoride for dental caries arrest in preschool children: A randomized controlled trial and microbiological analysis of caries associated microbes and resistance gene expression

Abstract

Objectives: The Stopping Cavities Trial investigated effectiveness and safety of 38% silver diamine fluoride in arresting caries lesions.

Materials and methods: The study was a double-blind randomized placebo-controlled superiority trial with 2 parallel groups. The sites were Oregon preschools. Sixty-six preschool children with ≥1 lesion were enrolled. Silver diamine fluoride (38%) or placebo (blue-tinted water), applied topically to the lesion. The primary endpoint was caries arrest (lesion inactivity, Nyvad criteria) 14-21days post intervention. Dental plaque was collected from all children, and microbial composition was assessed by RNA sequencing from 2 lesions and 1 unaffected surface before treatment and at follow-up for 3 children from each group.

Results and conclusion: Average proportion of arrested caries lesions in the silver diamine fluoride group was higher (0.72; 95% CI; 0.55, 0.84) than in the placebo group (0.05; 95% CI; 0.00, 0.16). Confirmatory analysis using generalized estimating equation log-linear regression, based on the number of arrested lesions and accounting for the number of treated surfaces and length of follow-up, indicates the risk of arrested caries was significantly higher in the treatment group (relative risk, 17.3; 95% CI: 4.3 to 69.4). No harms were observed. RNA sequencing analysis identified no consistent changes in relative abundance of caries-associated microbes, nor emergence of antibiotic or metal resistance gene expression. Topical 38% silver diamine fluoride is effective and safe in arresting cavities in preschool children.

Clinical significance: The treatment is applicable to primary care practice and may reduce the burden of untreated tooth decay in the population.

Keywords: Anti-infective agents; Cariostatic agents; Dentin/pathology; Human; Prospective studies; Treatment outcome.

Figure 1. Flow chart of Stopping Cavities Trial

Figure 2

Changes in microbes following SDF treatment. Species are plotted on the horizontal axis by the log2 change in relative abundance following treatment in the SDF treatment group, relative to the placebo group. The top panel plots the p-value of the change, with labels for species with an estimated false discovery rate <0.01 after adjusting for multiple testing. The lower panel plots the mean abundance for each species. FDR: false discovery rate; FC: fold change; Δ: change; SDF: silver diamine fluoride.