**4. Current level of evidence**

### **4.1 Fluoride varnish**

A myriad of *in-vivo* and *in-vitro* studies have been carried out to study the efficacy of preventive measures against white spot lesion formation during orthodontic treatment. Fluoride varnish has by far the strongest evidence base. The potential of fluoride varnish has been evaluated *in-vitro* (Adriens *et al.,* 1990; van der Linden and Dermaut, 1998; Todd *et al.,* 1999; Demito *et al.,* 2004) as well as *in-vivo* (Vivaldi-Rodrigues *et al*., 2006; Øgaard *et al.,* 2001). Generally, investigations carried out *in-vitro* indicate a moderate to strong beneficial effect of the tested varnishes on enamel demineralization. Two *in-vivo* studies have emerged. In a split-mouth prospective study, there was 44.3% less demineralization noted for teeth that had been treated every 12 weeks with fluoride varnish during orthodontic treatment (Vivaldi-Rodrigues *et al.,* 2006). In a double-blinded randomized placebo-controlled trial, Stecksén-Blicks et al. reported that although fluoride varnish did not totally prevent white spot lesion formation, the incidence was significantly reduced in the fluoride varnish group. In addition to differences in study design, the frequency of fluoride application also varied among the studies. Stecksén et al. applied the fluoride varnish at six week intervals, the typical appointment interval for most orthodontic patients.

White-Spot Lesions in Orthodontics: Incidence and Prevention 319

Still, the authors pointed out that the remineralization that occurred with CPP-ACP

As for ACP bonding cement products like Aegis-Ortho, there are currently no published comparative studies on its ability to prevent white spot lesions in the peer-reviewed literature. Two reports detail the questionable bond strength of ACP-containing cement. In spite of its potential benefits, frequent bond failures with ACP-cement have been reported. An *in-vitro* study with an earlier generation of Aegis-Ortho showed that orthodontic brackets bonded to teeth with an ACP-containing composite material failed at significantly lower forces than brackets bonded to teeth with a conventional resin-based composite orthodontic cement (Dunn, 2007). Another *in-vitro* study found that brackets bonded with the conventional Transbond XT had more than two times the shear bond strength in comparison to brackets bonded with Aegis-Ortho cement (Foster *et al.,* 2008). In evaluating the current evidence base for ACP and its various products, the number of published *in-vitro* and *in-vivo* trials is clearly underwhelming. In a 2008 systematic literature review published in the Journal of the American Dental Association (JADA), the authors concluded that there is insufficient clinical trial evidence to make a recommendation regarding the long-term effectiveness of casein derivatives, specifically CPP-ACP, in preventing caries *in-vivo*

Of all the treatments for incipient caries lesions during orthodontic treatment, agents with fluoride including varnish have the highest level of evidence. Multiple laboratory and clinical studies have demonstrated its efficacy. Highly-filled resin sealers like Pro-seal are relatively new, although the results from a few *in vitro* studies have demonstrated impressive results. On the other hand, a clinical study on its demineralization prevention has not yet surfaced. At this juncture, the evidence level for ACP products like CPP-ACP paste or ACP resin bonding cement is low. There is a clear need for more independent research of casein derivatives like CPP-ACP to make conclusions about its efficacy in caries

In terms of the clinical status quo for prevention of incipient caries lesions during orthodontic treatment, one has to first reference the AAO sponsored informed consent form, in which there is an emphasis on excellent oral hygiene, regular visits to the general dentist, and access to fluoridated water (AAO, 2009). In looking at practice trends, a recent survey by the Journal of Clinical Orthodontics does provide some information about the usage of some of the preventive measures previously outlined (Keim *et al.,* 2008). Despite its proven efficacy, only 9.3% of orthodontists deliver fluoride varnish to their patients. The article also mentions that only 7.4% of orthodontists employ the fluoride-releasing glass ionomer adhesive for bracket bonding, which is understandable given its questionable physical properties. There were no data in the article detailing the usage of ACP products or resin sealers. In any event, the fact that more than half of orthodontic patients develop incipient

treatment was generally more esthetic than with the fluoride rinse.

**4.3.2 ACP-containing bonding cement** 

(Azarpazhooh and Limeback, 2008).

**5. Summary of evidence** 

prevention.

**6. Clinical status quo** 

#### **4.2 Resin sealer**

After less successful earlier sealers, findings about the application of a filled-resin sealer (Pro-seal) have been published in the literature. One *in-vitro* study using an acid challenge found that demineralization was significantly less with Pro-seal treatment, compared to an untreated enamel surface (Hu and Featherstone, 2005). In fact, the demineralization levels established by microhardness profiles showed that the Pro-seal group had 98% less demineralization than the control group. This study also featured a group of teeth treated with fluoride varnish. While both the Pro-seal and fluoride varnish had significantly less demineralization than the control group, the sealer had significantly less demineralization than the varnish. Furthermore, the study also found that Pro-seal can stand up to acid challenge and toothbrush abrasion in a laboratory environment. These outcomes were corroborated by another *in-vitro* study, that also found that the filled-resin sealer (Pro-seal) provided significantly more protection than either fluoride varnish or an unfilled resin sealer, with a 92% reduction in lesion depth compared with the controls using polarized light microscopy (Buren *et al.,* 2008). In looking at its supposed fluoride release, one study found that Pro-seal released fluoride ions in a sustained way – with significantly decreasing amounts over a 17-week period, though this release was measured to be sub-ppm (Soliman *et al.,* 2006). Despite some favorable results with *in-vitro* models, no *in-vivo* trials with Proseal have been published in the literature.

#### **4.3 Amorphous calcium phosphate (ACP)**

#### **4.3.1 CPP-ACP paste**

Due to the early stages of this technology, published independent research on the ACP products like MI Paste is limited. Generally, the studies on caries prevention with CPP-ACP consist of *in-situ* caries models with gums, mouthrinses, or lozenges (Iijima *et al.,* 2004; Reynolds *et al.,* 2003). In addition, the vast majority of these studies were carried out by the same group that first isolated CPP-ACP at the University of Melbourne, Australia. For example, using topical applications of CPP-ACP via sugar-free chewing gum and mouthrinse, Reynolds et al. showed that CPP-ACP incorporated into dental plaque can significantly increase the levels of plaque calcium and phosphate ions (Reynolds *et al.,* 2003). Conversely, an *in-vitro* study carried out by an American group found that while fluoride 5000 ppm paste had a statistically significant protective effect against demineralization on enamel sections, MI Paste had no effect (Pulido *et al.,* 2008).There are two published studies that examine the role of CPP-ACP paste in orthodontics. In an *in-vitro* study that assessed the demineralization around bonded molar tubes on extracted third molars, a mild decrease in demineralization was found with the application of CPP-ACP (Sudjalim *et al.,* 2007). On the other hand, the authors of this very article recommended combining CPP-ACP with a fluoride gel to enhance the treatment effect. For the most part, clinicians loyal to the CPP-ACP protocol apply it without a fluoride gel, and the brochures by the manufacturer make no mention of additional rinses or gels. Andersson et al. conducted an *in-vivo* postorthodontic treatment study, in which they compared the remineralization capabilities of 0.05% Sodium Fluoride mouthwash and the application of Topacal (CPP-ACP topical cream) on patients with white spot lesions. The study found significant remineralization with both protocols, and found no significant differences between the groups over time. Still, the authors pointed out that the remineralization that occurred with CPP-ACP treatment was generally more esthetic than with the fluoride rinse.
