Silver Diamine Fluoride Treatment Considerations in Children's Caries Management Brief Communication and Commentary

Abstract

By arresting and preventing caries, SDF offers an alternate care path for patients for whom traditional restorative treatment is not immediately available. Current data from controlled clinical trials encompassing more than 3900 children, indicates that biannual application of SDF reduces progression of current and risk of subsequent caries. This commentary highlights the best evidence from systematic reviews and clinical trials for clinicians to consider the benefits, risks and limitations as they implement SDF therapy on young children.

Background

In the U.S., children's caries experience¹, inequity², and cost of care³ all increased significantly over the last 20 years. This suggests that the health systems, the current modes of therapy, and/or barriers to care inhibit effective caries control and prevention.

Consider early childhood caries (ECC) as one example of the challenges. Behavioral issues routinely complicate or prevent restorative treatment of ECC in young children. Yet, if left untreated, the disease progresses producing pain, has a negative impact on the quality of life, and in extreme cases can be life threatening. Further, because of the barriers to accessing dental care, vulnerable populations go through life with untreated disease⁴.

In developed countries, uncooperative children have the options of care delivered with conscious sedation, or in an operating room with general anesthesia. Both increase the risks and cost of treatment and restorative care does not address the underlying bacterial infection. Consequently, there is a high recurrence of lesions following restorative care⁵.

Numerous systematic reviews of human randomized controlled trials now suggest multiple preventive interventions as alternates to the traditional methods of restorative care.^{4, 6, 7} One of those interventions, silver diamine fluoride, is unique in both killing the bacteria and hardening the teeth, thus both arresting and preventing caries. It appears to be almost twice as effective as fluoride varnish for caries arrest ⁶. The U.S. Food and Drug Administration approved the use of SDF in 2014 as a device for the treatment of dentin sensitivity on patients 21 and older. Thus use of SDF for caries prevention or arrest is off-label, similar to fluoride varnish.

Interestingly, a 2016 survey of pediatric training programs indicated that while greater than 90 percent of programs teach and use fluoride varnish, less than 30 percent of programs use SDF ⁸. Here we examine the application of SDF for caries arrest and prevention in children as a pathway to effective preventive care and provide a suggested protocol based on the current evidence. In addition to the clinical benefit for patients, application of SDF for children with behavioral issues should reduce the clinician's potential legal risk⁹.

To identify the current best evidence for using SDF in arresting or preventing caries we searched PubMed for randomized controlled trials published in English using SDF in children. We identified 10 clinical trials, carried out in six countries, examining the application of SDF in 3,904 children^10-19 (Table 1). Our commentary is based on their results and protocols. The methods differed between trials in terms of: teeth (primary or permanent; anterior or posterior); frequency of application (one time, two times, or three times per year); SDF concentration (10 percent to 38 percent); presence and extent of caries; caries removal; residence time for SDF; children's age; length of follow up; geographic location of study; control groups; and outcome measured: caries arrest (assessed by hardened and darkened dentin) and/or caries prevention (assessed by new caries). Even with all this variability, in nine out of 10 studies, SDF performed better than controls in caries arrest and/or prevention. Finally, using the manufacturer's MSDS data sheets we calculated and compared the amount of fluoride delivered per dose for both SDF and fluoride varnish.

Table 1.

Description and Clinical Details of Randomized Control Trials on Children

Study	Chu et al 200210	Yee et al 200912	Zhi et al 201214	Dos Santos et al 201215	Duangthip et al 201518	Fung et al 201619	Llodra et al 200511	Braga et al 200913	Liu et al 201216	Monse et al 201217
Location	China	Nepal	China	Brazil	Hong Kong	China	Cuba	Brazil	China	Philipinnes
Dentition studied	Primary anterior only	primary	Primary anterior and posterior	Primary	Primary anterior and posterior	Primary anterior and posterior	Primary cuspids, molars and permanent 1rst molars	Permanent 1st molars	Permanent 1st molars	Permanent 1st molars
Caries effect studied	Arrest	Arrest	Arrest	Arrest	Arrest	Arrest	Arrest and prevention	Arrest	Prevention	Prevention
Groups compared	1.SDF (38%) 1x/year with caries removal 2.SDF (38%) 1x/year without caries removal 3.FV 5% 4x year with caries removal 4.FV 5% 4x year without caries removal 5.water control	1. SDF (38%) 1x followed by tannic acid as reducing agent 2.SDF (38%) 1x alone 3.SDF (12%) 1x alone 4.no treatment	1.SDF (30%) 1x/year 2.SDF (30%) 2x/year 3.GI (Fuji VII) w/conditioner 1x/year	1.SDF(30%) 1x 2.ITR (Fuji IX) w/conditioner 1x.	1.SDF (30%) 1x/year 2.SDF (30%) 1x/week for 3 weeks 3.FV (5%) 1x/week for 3 weeks	1.SDF (38%) 2x/year 2.SDF (38%) 1x/year 3.SDF (12%) 2x/year 4.SDF (12%) 1x/year	1.SDF (38%) 2x/year 2.No treatment	1. SDF (10% ) 3x at 1 week interval 3. GI (Fuji III) sealant 1x 3. Cross tooth-brushing Non cavitated caries lesions On each child one molar was assigned to each group.	1.SDF (38%) 1x/year 2.Resin sealant 3.5% NaF varnish 2x year 4.yearly placebo Deep fissures or non-cavitated early lesions. Each child got same tx. in all molars.	1. SDF (38%) 1x on sound and cavitated molars. 2.ART (high viscosity Ketac molar) on sound and cavitated molars. 3.no treatment (NT) Some schools had toothbrushing programs and some didn't
Main findings	1.SDF was more effective than FV or control. . (65% arrested lesions for SDF groups vs. 41% for FV groups vs. 34% for control) 2.Caries removal had no effect. 3.Control group developed more new caries than treatment groups.	1.SDF was more effective than controls (31% arrested lesions for SDF groups vs. 22% for SDF 12% vs. 15% for control) 2.Tannic acid had no effect 3.Arrest benefit decreases over time.	1.SDF and GI are equally effective. (91% arrested lesions for SDF 2x/year vs. 79% SDF 1x/year, vs. 82% GI 1x/year) 2.Increasing frequency of SDF (2x/year) increases caries arrest. 3.Anterior teeth and buccal/lingual surfaces are more likely to become arrested.	1. SDF was more effective than ITR. (67% arrested lesions in SDF group vs. 39% in control)	1. SDF 1x/year and SDF 3 consecutive weekly applications were more effective than FV. (40% arrested lesions with SDF 1x/year vs.35% with only 3 consecutive SDF applications vs. 27% with FV)	1. SDF 38% 2x/year was more effective than SDF 38%1x/year, SDF12% 2x/year or 1x/year (74% arrested lesions vs. 64%, 55% and 50% respectively)	1.SDF 2x/year was more effective for caries arrest than controls. (85% arrested lesions with SDF vs. 62% in control) 2.SDF was effective for caries reduction in both primary and permanent teeth. (0.29 surfaces with new caries in SDF group vs 1.43 in control in primary teeth and 0.37 vs 1.06 in permanent molars)	1.SDF was more effective than toothbrushing or GI at 3 and 6 months. 2.All equally effective in controlling initial (non-cavitated) occlusal caries at 30 months.	1.The 3 active treatments are effective in caries prevention. (progression of caries into dentin was 2.2% for SDF, 1.6% for sealant, 2.4% for FV vs. 4.6% for control) 2.Control group developed more dentin caries than treatment groups.	1.ART sealants were more effective than a single application of SDF (caries increment in the brushing group was: .08 for NT .09 for SDF .01 for sealants in non brushing group: .17 for NT .12 for SDF .06 for sealants) 2.Caries increment was lower in tooth-brushing group.
Additional findings	1. arrested lesions looked black without changing parental satisfaction (93% of parents didn't mention a difference)	1.single SDF application prevented half of arrested surfaces at 6 months from reverting to active lesions again over 24 months. 2.no complaints from parents or children to SDF	1.GI provides a more esthetic outcome. 2.only 3.5% retention of GI after 24 months still provides caries arrest 3.45% of parents in all groups were satisfied with appearance.	1.43% of GIC fillings were lost at 6 months and dentin was soft. 2.higher rate of failure when GIC involved multiple surfaces.	1. lesions in anterior teeth, buccal/lingual surfaces and lesions with no plaque had a higher chance to become arrested	1.lesion site was significant, with lower anteriors having the highest rates of arrest followed by upper anteriors, lower posterior and upper posterior. 2.Lesions with visible plaque and large lesions had lower chance of becoming arrested.	1. SDF showed more efficacy to arrest decay in deciduous teeth than permanent teeth.	1.retention rates for GI sealants were 32% at 6 months and 9% at 30 months 2.GI sealants were more time consuming that SDF application.	1.teeth with early caries at baseline were more likely to develop dentin caries after 24 months 2.46% sealant retention	1. retention rate for sealants was 58% after 18 months.
SDF Clinical Application Protocol	*2 treated groups had caries removal and 2 didn't. *doesn't specify SDF amount used or time of exposure	*no caries removal *one drop of SDF applied for 2 min to carious surfaces and dried with cotton pellet. *no eat or drink for 1 hr after	*minor excavation *doesn't specify SDF amount used or time of exposure *no eat or drink for 30 min after	*no caries removal *doesn't specify SDF amount used; *cotton roll isolation, Vaseline on gingiva, SDF applied for 3 min and rinse and spit *no eat or drink for 1 hr.	*no caries removal *doesn't specify SDF amount used or kind of isolation. *SDF rubbed for 10 sec. - no eat or drink for 30 min.	* doesn't specify SDF amount used, time of exposure, or kind of isolation	*minor decay excavation on permanent molars only. *doesn't specify SDF amount used *cotton roll isolation, SDF applied for 3 min and wash for 30 sec.	*no caries removal *doesn't specify SDF amount used *cotton roll isolation and petroleum jelly on gingiva, SDF applied for 3 min and wash for 30 seconds. *no eat or drink for 1 hr.	*doesn't specify SDF amount used, time of exposure, or whether it was rinsed or not *cotton roll isolation *no eat or drink for 30 min.	*doesn't specify SDF amount used, SDF rubbed for 1 min. followed by tannic acid, dried with cotton pellet and covered with vaseline *cotton roll isolation
Adverse effects	None	None	None	None	None	None	0.1% Gingival irritation	None	None	None
Duration of study	30 months	24 months	24 months	12 months	18 months	18 months	36 months	30 months	24 months	18 months
Baseline caries	3.92 dmfs (active anterior lesions)	6.8 dmfs (active lesions)	5.1 dmft (3 random teeth/child)	3.8 dmft	4.4 dmft 6.7 dmfs	3.84 dmft 5.15 dmfs	3.2 dmft	Non-cavitated molar occlusal	No cavitated lesions	At least one sound permanent molar
Background F exposure	Low F exposure reported use of F toothpaste	Low F exposure Provided F toothpaste	Low F exposure low access to F toothpaste	Low F exposure access to F toothpaste	F water F toothpaste	Low F exposure F toothpaste	Low F exposure + 0.2% NaF rinse in school every other week	Low F exposure Provided F toothpaste	Low F exposure Provided F toothpaste	Low F exposure Provided F toothpaste
# subjects at baseline	375	976	212	91	304	888	425	22 children, 66 molars	501	1016
# subjects at endpoint	308	634	181	?	275	831	373	?	485	704
Exams after baseline	X 6 months	1,12 and 24 months	X 6 months	X 6 months	X 6 months	X 6 months	X 6 months	3, 6, 12, 18 and 30 months plus X rays at 6, 12 and 30 months	X 6 months	18 months

^*low F exposure = low F in the water, no other professionally applied fluorides nor fluoride supplements.

Commentary

The most effective treatment was 38 percent SDF twice per year, which lead to almost 80 percent reduction in both caries progression¹⁹ and subsequent caries on treated teeth⁷, which is twice that of fluoride varnish^{10, 11}.

The results from RCTs (Table 1) can serve as an initial foundation for clinical practice implementation. The combined study results suggest that a reasonable protocol for initial SDF use might be the following:

• Twice yearly application of SDF 38 percent is a reasonable starting point.

• SDF is a viable treatment alternative for high-risk, high-need patients for whom cooperation is a concern.

• Use of a detailed informed consent to fully convey the benefits and limitations of this therapy is recommended. Clinicians might consider using clinical photographs with the informed consent.

• Thirty-eight percent SDF for arresting caries lesions and preventing new caries from forming in school children is effective in both primary and permanent dentitions (65.9 percent dentine caries arrest overall ¹¹).

• No caries excavation or removal is necessary.¹⁰ However, as direct contact of the solution with dentin is required, surfaces clean of food debris are desirable.

• Study application time ranged from 10 seconds to three minutes with and without drying and with and without rinsing following the application. The manufacturer's recommendations of 30 to 60 seconds application with air-drying is consistent with the best study results for caries arrest.

• Initial use on posterior pits, fissures, and caries might be considered given concerns about anterior esthetics.

• For anterior esthetics, SDF could be followed by glass ionomer prior to restorative treatment further reducing risk of caries re-occurrence.

• Posterior teeth and large cavities may have less chances of arrest with one-time application^{14, 19}. However, in most clinical settings, individualized evaluation of the caries and caries arrest on specific surfaces is feasible, so re-application can be tailored to the needs to each patient. A one-month follow-up to evaluate arrest and need for re-application on active treated carious surfaces should be advantageous, similar to a post-op visit after restorative or surgical procedures

• The combination of SDF and fluoride varnish remains an open question. Fluoride varnish is used primarily to prevent smooth surface caries and remineralize early enamel lesions. Conversely, SDF is used primarily for frank carious lesions. Therefore, their combinatorial use may be additive or synergistic, and remains to be determined. One potential solution is alternating their use at three-month intervals.

• Anterior teeth have higher rates of arrest.^{14, 19} This could be due to the fact that they are more easily cleansable, or that surfaces exposed to light may result in more active silver precipitation.

Anecdotal evidence reports that in clinical settings, the use of a curing light after drying seems to improve arrest in posterior areas that are not exposed to natural light, as light-cured surfaces immediately turn dark. Formal research is needed to investigate if the arrest in these lesions is at least as effective and sustainable as the rates reported in the clinical trials.

The foregoing would appear to meet the needs of pediatric program directors⁸. More than 88 percent agree that SDF can be used to arrest caries in high-risk patients in primary (87 percent agree) and permanent (66 percent agree) teeth. There is greater than 90 percent agreement that SDF will be useful in treating patients who have difficulty receiving conventional treatment (e.g.: pre-cooperative, behavioral, or medically fragile). Paradoxically, less than 50 percent agree that SDF will be useful for caries prevention in incipient lesions.

The barriers to SDF use identified by program directors⁸ all appear to contradict the current best evidence identified here. They include the following: (1) Parental acceptance: Greater than 90 percent believe that parental acceptance is a concern. Where studied^{10, 12, 14} parental concern to the staining was less than seven percent, but we acknowledge the fact that these studies took place in settings where esthetic concerns may be different than US standards. It is our experience that parents with limited options for treatment due to behavioral or medical limitations, are willing to accept the treatment. Studies are under way to formally explore parental acceptance. (2) Off label use: More than 60 percent were concerned about off label use. In fact, fluoride varnish, which has become the gold standard of caries prevention for children, has been used off label for decades, and is used in 100 percent of pediatric dental programs. (3) Standard of care: More than 60 percent were concerned that SDF use is not a standard of care. Based on the human randomized controlled trials, published in peer reviewed journals reported here, SDF meets the legal standard of care in more than 34 states⁹. (4) Evidence based: More than 60 percent felt that the evidence was insufficient. Skeptics might offer clarity on protocols that would improve on those reported here covering more than 3,900 children treated globally under a variety of conditions. (5) Reimbursement: More than 70 percent were concerned about reimbursement. The American Dental Association billing code for interim caries arresting medication application is D1354, and fees are dentist-patient dependent. (6) Resident training: More than 50 percent were concerned about training residents. With the wealth of systematic reviews and human clinical trials, program directors have a unique evidence-based dentistry teaching opportunity. (6) Obtaining product: More than 50 percent were concerned about obtaining the product. Silver diamine fluoride (trade name Advantage Arrest) is available from Elevate Oral Care LLC, Fla, US. (7) Cost: Almost 60 percent were concerned about cost. We estimate the material cost to be approximately $0.91 per patient ($0.80 for the SDF for one drop of SDF sufficient to treat eight teeth, and $0.11 for the micro brush).

The U.S. Affordable Care Act's triple aim calls for: increasing access, improving health, and reducing costs. SDF meets all three aims. The most notable aspects of SDF are its efficacy, ease of use, and low cost. SDF takes 30 seconds to apply, reduces caries progression and subsequent caries by 60- 80 percent in primary and permanent teeth, and we estimate that the cost is less than one dollar per child for supplies.

SDF also meets the U.S. Institute of Medicines six quality aims²⁰ of: safe (e.g.: without adverse events), effective (e.g.: reduces caries progression and subsequent caries by almost 80 percent on treated teeth); efficient (e.g.: can be applied by health professional in any location where children learn, play, and pray), timely (e.g.: takes less than 30 seconds), patient centered (e.g.: meets immediate needs of child in one treatment); equitable (e.g.: is equally effective for all socioeconomic groups, races, ethnicities and cultures).

Biologically, silver diamine fluoride is a bi-functional agent. The silver directly kills caries causing bacteria, while silver and fluoride interact synergistically to form fluorapatite, hardening the teeth preventing further demineralization⁶. More specifically, at the molecular level, silver ions interact with sulfhydryl groups of proteins and DNA altering hydrogen bonding, thus inhibiting respiratory processes, cell wall synthesis, and cell division.⁶ At the macro level, these interactions effect bacterial killing and inhibit biofilm formation. Simultaneously the silver precipitates onto the surface of the tissues creating the brown-black surface especially in dentin, which together with the hardening of the tissue are the clinical indications of “caries arrest”.

Finally, there is some concern about the potential adverse events from SDF use. A primary concern is the child's fluoride dose. As indicated in Table 2, one drop of SDF, enough to treat six teeth, contains approximately half the fluoride level of the smallest unit dose used for a fluoride varnish application. Clinicians are also concerned about parents’ response to the tooth discoloration. Most parents in the trials studied, did not mind the staining associated with caries arrest in the communities where it was tested. As seen in Figures 1 and 2, the dentinal carious tissues color changes from dark brown to black. Porous incipient enamel lesions can darken as well. As with all care, a detailed informed consent delineating the benefits and potential esthetic limitations of this therapy are needed. Clearly the esthetic concern is paramount if one applies SDF to non-cavitated porous enamel lesions on anterior teeth. Another concern is the pulpal or gingival reaction. In the identified studies, no children exhibited negative reactions to the treatment, no adverse pulpal responses, and only 0.1 percent of children noted slight gingival irritation.

Table 2.

Fluoride content in SDF and Fluoride Varnish commercial unit doses

Fluoride product	Unit dose	Concentration	F ion mg/ml	F ion mg/dose
SDF 38%	1 drop (0.05 ml)	44,800 PPM	44.8	2.24
Fluoride Varnish 5% NaF	0.25 ml	22,600 PPM	22.6	5.65
	0.4 ml	22,600 PPM	22.6	9.04
	0.5 ml	22,600 PPM	22.6	11.3

F content equivalence (aprox.): 2 drops SDF = small (.25 ml) FV

FIGURE 1. anterior/posterior staining.

Esthetic restorations can be used at a future date when the caries process is under control, after the advantages provided by immediate arrest have had an effect: reduced sensitivity, improved hygiene, improved gingival health, enamel and dentin remineralization, tissue preservation.

FIGURE 2. Posterior staining.

Esthetic restorations can be used at a future date when the caries process is under control, after the advantages provided by immediate arrest have had an effect: reduced sensitivity, improved hygiene, improved gingival health, enamel and dentin remineralization, tissue preservation.

Conclusions

In summary, SDF appears to be a useful immediate treatment for children who can't receive traditional restorative treatment for dental decay. It is effective for caries arrest and prevention of new lesions on the teeth where it is applied, and is a minimal intervention treatment that is safe and affordable.

Given the foregoing, it might be expected that SDF will be widely implemented for caries control to meet our patient's needs, as well as national goals of both the Affordable Care Act's and the Institute of Medicine's quality aims.