Fight Back! Proactively Addressing the Caries Process

The majority of the Germans only change their toothbrush every five to six months—not often enough to prevent unpleasant side-effects. According to a new study, using a toothbrush for a period of six months may lead to gingivitis, which in turn increases the risk of other diseases.
For the study, researchers from the University of Göttingen divided participants into two test groups. Over a period of six months, the members of one group cleaned their teeth with one toothbrush, while the participants in the other group were given a new one every four weeks.

After six months, the scientists found an increase in gingival inflammation in the group that had not changed toothbrushes. The participants in the other group showed a better overall state of oral hygiene at any time in the test phase than at the beginning of the study, particularly concerning plaque.

“The results of the study are of significant relevance to oral health in Germany,” said Dr Dirk Ziebholz, research associate at the Department of Preventive Dentistry, Periodontology and Cariology at the University of Göttingen and leader of the study. “Gingivitis can lead to other problems such as periodontitis."

According to the GfK Group, a German market research company, Germans bought an average of 2.5 toothbrushes each in 2010. However, the recommended amount is four. Families in particular tend to change their toothbrushes only rarely (2.3 toothbrushes per year). With 4.5 toothbrushes, single professionals change their toothbrush even more frequently than every three months.

Most Germans change their toothbrush when the bristles are worn-out (70 per cent) or when they are concerned that their toothbrush may no longer be hygienic (66 per cent), according to GfK.

The study was conducted in collaboration with Dr. Best, a brand of GlaxoSmithKline.

Researchers from India have successfully tested a method that could help dentists to identify children who are at risk of developing Early Childhood Caries, the highly virulent form of tooth decay. In clinical tests conducted on pre-schoolers from Mangalore in southern India, they reported a link between the children’s bitter taste perception of a drug used in the treatment of autoimmune disease and their oral health status.
Oral bacteria attack children early
According to the researchers, who recently published their results in the Indian Journal of Human Genetics, children who reacted to 6-n-propylthiouracil (PROP) also showed a greater dislike of sweet foods and fewer signs of tooth decay compared with those who could not taste the compound. They also had fewer dental problems than those who did not react to it, the researchers said.

They concluded that taste perception could be used as a future diagnostic tool to identify children at risk of developing dental caries at an early age. “Tasters or sweet dislikers might avoid sweet food because their oral sensations are too intense, thus making tasters less prone to decay,” they stated in the paper.

Besides testing the perception of taste through questionnaires, the researchers observed the facial expressions of the children tested when exposed to the drug.

PROP, which is used in the treatment of Graves’ disease, among other thyroid diseases, is perceived as bitter tasting by the majority of people. However, studies have suggested that one out of three is insensitive to the compound. The ability to taste the drug is controlled by a specific gene that functions as a taste receptor.

First approved in the late 1940s, PROP is currently classified as a Pregnancy Category D drug by the US FDA and, therefore, its use is limited. Reported side-effects include increased risk of agranulocytosis and liver damage, including complete renal failure.

According to figures from Yale University, five to ten children die every year from taking PROP

SMaRT Replacement Therapy™ is designed to be a painless, one-time, five-minute topical treatment applied to the teeth that has the potential to offer lifelong protection against tooth decay caused by S. mutans, the principal cause of this disease. We have extensively and successfully tested the SMaRT strain for safety and efficacy in laboratory and animal models, and we are in the process of commencing a second Phase 1 clinical trial with an attenuated version of our SMaRT Replacement Therapy.

Market Opportunity

Dental diseases are the most prevalent chronic infectious diseases in the world, affecting up to 90% of schoolchildren and the vast majority of adults. Annual expenditures on the treatment of dental caries in the U.S. are estimated to be $40 billion a year according to the Dental, Oral and Craniofacial Data Resource Center. Tooth decay is characterized by the demineralization of enamel and dentin, eventually resulting in the destruction of the teeth. Dietary sugar is often misperceived as the cause of tooth decay; however, the immediate cause of tooth decay is lactic acid produced by microorganisms that metabolize sugar on the surface of the teeth. Studies suggest that of the approximately 700 oral microorganisms, S. mutans , a bacterium found in virtually all humans, is the principal causative agent in the development of tooth decay. Residing within dental plaque on the surface of teeth, S. mutans derives energy from carbohydrate metabolism as it converts dietary sugar to lactic acid which, in turn, promotes demineralization in enamel and dentin, eventually resulting in a cavity. The rate at which mineral is lost depends on several factors, most importantly the frequency and amount of sugar that is consumed.

Fluoride is used to reduce the effect of lactic acid-based demineralization of enamel and dentin. Despite the widespread use of fluoride in public water systems, toothpastes, dental treatments and sealants, and antiseptic mouth rinses, over 50% of 5-to-9-year-olds and almost 80% of 17-year-olds in the United States have at least one cavity or filling, according to the U.S. Surgeon General. In addition to non-compliance with the behavioral guidelines of the American Dental Association such as routine brushing and flossing, there are several factors that are likely to increase the incidence and frequency of tooth decay, including increasing consumption of both dietary sugar and bottled water. Bottled water generally does not contain fluoride, and thus does not impart any of the protective effects of fluoridated water from public systems. In 2008, U.S. consumers drank more bottled water than any other alcoholic or non-alcoholic beverage, with the exception of carbonated soft drinks, according to the Beverage Marketing Corporation.

 replacement therapy technology is based on the creation of a genetically altered strain of S. mutans, called SMaRT, which does not produce lactic acid. Our SMaRT strain is engineered to have a selective colonization advantage over native S. mutans strains in that SMaRT produces minute amounts of a lantibiotic that kills off the native strains but leaves the SMaRT strain unharmed. Thus SMaRT Replacement Therapy can permanently replace native lactic acid-producing strains of S. mutans in the oral cavity, thereby potentially providing lifelong protection against the primary cause of tooth decay. The SMaRT strain has been extensively and successfully tested for safety and efficacy in laboratory and animal models.

SMaRT Replacement Therapy is designed to be applied topically to the teeth by a dentist, pediatrician or primary care physician during a routine office visit. A suspension of the SMaRT strain is administered using a cotton-tipped swab during a single five-minute, pain-free treatment. Following treatment, the SMaRT strain should displace the native, decay-causing S. mutans strains over a six to twelve month period and permanently occupy the niche on the tooth surfaces normally occupied by native S. mutans.

Tooth decay is a largely preventable disease through implementation of an appropriate oral care hygiene program including brushing, flossing, irrigation, sealants and antiseptic mouth rinses. Nevertheless, tooth decay remains the most common chronic infectious disease in the world, which indicates that the lack of patient compliance with an overall oral care regimen remains a critical issue in tooth decay prevention. We believe that SMaRT Replacement Therapy addresses the issue of patient compliance by requiring only a one-time, five-minute treatment for the potential lifelong prevention of tooth decay.

The SMaRT strain has been extensively and successfully tested in the laboratory as well as in animal models , and has demonstrated the following:

 No lactic acid creation under any cultivation conditions tested;

 Dramatically reduced ability to cause tooth decay;

 Genetic stability as demonstrated in mixed culture and biofilm studies and in rodent model studies;

 Production of a level of MU1140 that is comparable to its wild-type parent strain, which was previously shown to readily and persistently colonize the human oral cavity;

 Aggressive displacement of native, decay-causing strains of S. mutans and preemptive colonization of its niche on the teeth of laboratory rats.

In addition, during preclinical and early-stage clinical testing of our SMaRT Replacement Therapy, we observed the following:

 No adverse side effects in either acute or chronic testing in rodent models;

 Colonization of the treated subjects following a five-minute application of SMaRT Replacement Therapy in our first Phase 1 study using the attenuated strain;

 No adverse side effects during our first Phase 1 study.

Manufacturing

The manufacturing methods for producing the SMaRT strain of S. mutans are standard Good Manufacturing Practice, or GMP, fermentation techniques. These techniques involve culturing bacteria in large vessels and harvesting them at saturation by centrifugation or filtration. The cells are then freeze dried or suspended in a pharmaceutical medium appropriate for application in the human oral cavity. These manufacturing methods are commonplace and readily available within the pharmaceutical industry. A single dose of our SMaRT Replacement Therapy contains approximately 10 billion S. mutans cells. The SMaRT strain grows readily in a variety of cultivation media and under a variety of common growth conditions including both aerobic and anaerobic incubations. The SMaRT strain can also utilize various carbon and nitrogen sources and is highly acid tolerant. There is no significant limitation to the manufacturing scale of our SMaRT strain other than the size of the containment vessel. For our first Phase 1 clinical trial, we engaged a contract manufacturer to produce an attenuated version our SMaRT strain, using a standard operating procedure provided by us that we believe is readily transferable to outside contract manufacturers with fermentation capabilities

An indicator to assess caries risk of infants is very important. One conventional risk indicator is the number and/or proportions of Streptococcus mutans, but this method reflects the existing situation and is not suitable for assessing caries risk of infants that have not yet been infected with S mutans. Researchers searched for an indicator for the establishment of S mutans. To evaluate the changes caused by the establishment of S mutans in the microbiota of the infant oral cavity, the authors monitored changes in the oral microbiota of 2 predentate infants over a 3-year period and in a cross-sectional study of 40 nursery school-aged children. Saliva was cultivated on nonselective blood agar, Mitis-Salivarius agar, and Mitis-Salivarius agar supplemented with bacitracin combined with identification of selected isolates. Two longitudinal observations suggested that S mutans establishment would induce a decrease in α-haemolytic bacteria in the microbial population of the oral cavity. This suggestion was compensated with the results of the study, and it was revealed that the establishment of 103 CFU/mL of S mutans in saliva might be predicted by a microbiota comprising less than approximately 55% of α-haemolytic bacteria. The authors conclude that a decrease in the proportion of α-haemolytic bacteria in the saliva of infants is applicable as an indicator to predict the establishment of S mutans and to assess dental caries risk. This information can serve as a background for planning dental care and treatment in the infants before infection with S mutans occurs.

A health committee in the United Kingdom may want to re-explore a recent decision.

The Advertising Standards Authority claimed the McDonald’s drink Fruitizz can be part of the five-a-day portions of fruit and vegetables. The five-a-day portions of fruits and vegetables is a program that encourages healthy and drinking for children.

This ruling comes in spite of the fact that the drink contains six teaspoons of sugar.

The drink comprises fruit juice concentrate, fizzy water, natural flavorings and potassium sorbate.

A serving size of 250 mL has roughly 100 calories and 25 g of sugar. These levels of sugar stem from the amount of fruit juice content. Still, these levels did not nullify its ability to be considered healthy, according to the authority that makes these rulings.

This issue was examined after a British commercial mentioned the drink’s health benefits.

The ruling calls into question the standards used to determine a food or beverage’s health value.

Based on various studies, sugary drinks have been determined to cause tooth decay and erosion. There are also various other problems that can result from sugary drinks.

Still, based on the health standards for the five-a-day guidance in the United Kingdom, this drink manages to meet the requirements.

The human mouth is a community bustling with microorganisms that live there. Little knowledge exists about what factors control which types that live there and which don’t. In a new study published in Genome Research, investigators have discovered environment has a more controlling stance on determining oral microbiota, an extremely important finding in the field of oral health.

The oral microbiome starts forming as soon as a person is born. We see a plethora of bacteria brought into our mouth during childhood and as an adult, although little knowledge is known about whether nature (genes), or nurture (environment) has a more powerful influence.

Due to differences in the oral microbiome in health and diseases such as bacteremia and endicarditis, there is a need for a better understanding of the factors that effect oral microbiota communities, in order for more efficient prevention and treatment plans.

During this study, the researchers sequenced the microbial DNA found in saliva samples of a group of twins, and then paired the DNA sequences in a database to see which types of bacteria existed in each individual.

Comparing the salivary microbiomes of identical twins with the same genetic make-up and a common environment, the scientists found that their salivary microbiomes were not notably more similar than those of fraternal twins who only share half the genes. Surprisingly, this finding points to the idea that genetic relatedness is not such an important role.

"We were also intrigued to see that the microbiota of twin pairs becomes less similar once they moved apart from each other," added Simone Stahringer, first author of the study.

It was also seen from samples over time that the salivary microbiome changed the most during adolescence, suggesting behavioral changes or puberty may have a significant influence.

The researchers also uncovered another surprising find, that there is a fundamental community of bacteria that exists in all humans.

Ken Krauter, senior author of the study, explains:

"Though there are definitely differences among different people, there is a relatively high degree of sharing similar microbial species in all human mouths."

The authors believe that this study has provided a framework for future studies of the factors that control oral microbial communities. With this knowledge, people can now better understand how oral hygiene, environmental subjection to substances, methamphetamines, and even food can impact these microbes.

Written by Sam Halabo, DMD
What causes white spots and why do they form? White spots are signs of demineralization underneath intact enamel. Bacteria produce acids which break down apatite to calcium and phosphate ions.1 When these ions are not replaced in the natural remineralization process, porosities are created within the enamel. This usually results in the underlying porosity becoming fluid-filled, developing the classic whitish discoloration associated with demineralization. This discoloration is the result of the difference in refraction of light through healthy enamel and fluid filled porosity.2 White spots can appear in primary or secondary teeth with differing intensities. Most commonly, white spot lesions are seen after orthodontic bands and brackets are removed. Some of the other causes of white spot lesions include fluorosis, hypocalcification, erosion, hypoplasia, xerostomia, tetracycline staining, and trauma. They can also be the result of arrested incipient decay that stopped progressing and remineralized.

Treatments
In the past, the primary approach to the treatment of white spots is remineralization using pastes, creams, and topical treatments. Some of these include fluoride therapy or some form of calcium phosphate paste. Teeth whitening may also be used as an option to alleviate the appearance of these white lesions but usually requires variable amounts of time. These modalities all have unpredictable degrees of success based upon published literature. Other more invasive approaches to dealing with white spot lesions include microabrasion, composite restorations, and veneers or crowns.

Diagnosis
In order to provide a good treatment plan, a proper diagnosis must be made. We have come to depend on visual examination as a primary diagnostic tool, along with probing of suspected surfaces in order to determine the location of areas of concern. Color, hardness, translucency, and opacity all play a role in diagnosing the presence of lesions.

The best way to do a visual analysis is to dry the teeth and then examine them under good lighting with high magnification. While hypocalcifications are visible wet or dry, incipient caries lesions are often visible only when enamel is dry. (Typically carious lesions are visible when dry but disappear when rewetted.) Also, the surface of an inactive white spot lesion is usually smooth and shiny, while a rough, chalky, and dull lesion can indicate an active caries lesion.
As we continue our search for minimally invasive techniques, a product called Infiltration Concept (ICON) was introduced in the United States in 2009 by DMG America. Designed to arrest the progression of incipient carious lesions, Icon gives us a great solution for treating white spot lesions with a simple technique as well. This is a great treatment for stopping early caries and removing opaque lesions, all without any drilling or need for local anesthesia. There is no shade matching necessary as this material blends with the tooth shade and eliminates the white lesions. This procedure has worked well repeatedly in our office. The procedure is simple and can even be done by auxiliary members (check your state dental practice laws).

This product fills and reinforces the pores of these lesions with a light-cured resin material. A very low-viscosity infiltrating resin (Icon-Infiltrant [DMG America]) is pulled deep into the pores of a lesion by way of capillary action. This resin fills the tooth and replaces the lost structure within the pores. The progression of caries is stopped as no further nutrients are allowed into the pores. Icon accomplishes this without changing the shade of the tooth or altering its shape. This procedure is ideally suited for patients with a history of orthodontic therapy, high acid exposure, and/or poor oral hygiene.

Icon is not indicated for patients with fluorosis, hypocalcification, erosion, tetracycline stain or trauma to the teeth. It is indicated for those lesions, both proximal and smooth surface, that are clearly the result of cariogenic bacteria. Simply put, it is indicated for lesions that are the result of acid demineralization of tooth structure.

In 2010, the Institute of Medicine (IOM) released a report that called for an increase in the recommended daily intake of vitamin D, but also said that the current body of research did not offer the evidence needed to confirm that vitamin D has the larger positive health effects its proponents claim it does.

Research has shown a positive link between vitamin D and oral and systemic health, the IOM noted; however, these studies have yielded "conflicting and mixed results and do not offer the evidence needed to confirm that vitamin D has these effects."

Now a new systematic review, conducted by Philippe Hujoel, PhD, DDS, MSD, MS, of the University of Washington School of Dentistry and School of Public Health, points to a positive association between vitamin D and lower rates of dental caries (Nutrition Reviews, November 9, 2012).

Vitamin D was first discovered in the early 1920s, and at least 20 prospective clinical studies evaluating its impact on dental caries were initiated in Europe, North America, and Asia over the next two decades, according to Dr. Hujoel. However, professional and governmental groups varied widely in their interpretation of the scientific evidence.

For example, the American Medical Association and the U.S. National Research Council concluded around 1950 that vitamin D was beneficial in managing dental caries, but the ADA said otherwise — based on the same evidence. In 1989, the National Research Council, despite new evidence supporting vitamin D’s caries-fighting benefits, called the issue "unresolved."

More recent reviews by the Institute of Medicine, the U.S. Department of Human Health and Services, and the ADA draw no conclusions on the vitamin D evidence as it relates to dental caries, Dr. Hujoel noted in a press release.

"Such inconsistent conclusions by different organizations do not make much sense from an evidence-based perspective," he said.

24 studies, 6 decades

For the Nutrition Reviews study, Dr. Hujoel analyzed 24 controlled clinical trials (CCTs) that met the inclusion criteria. The CCT quality was quantified using a 21-item questionnaire and content-specific measures such as method of treatment assignment, setting, clinician blinding, use of placebo, commercial funding source, and study duration.

The 24 CCTs included in the study spanned the 1920s to the 1980s and were conducted in the U.S., U.K., Canada, Austria, New Zealand, and Sweden in institutional settings, schools, medical and dental practices, or hospitals. All told, the CCTs encompassed nearly 3,000 participants between the ages of 2 and 16 years.

The trials increased vitamin D levels in these children through the use of supplemental ultraviolet (UV) radiation or by supplementing the children’s diet with cod liver oil or other products containing the vitamin.

"My main goal was to summarize the clinical trial database so that we could take a fresh look at this vitamin D question," Dr. Hujoel said.

These trials showed that vitamin D was associated with a 47% reduction in the incidence of tooth decay, he noted. No robust differences could be identified between the caries-preventive effects of UV therapy and nutritional supplementation with either vitamin D2 or vitamin D3.

"The analysis of CCT data identified vitamin D as a promising caries-preventive agent, leading to a low-certainty conclusion that vitamin D in childhood may reduce the incidence of caries," Dr. Hujoel concluded.

The vitamin D question takes on greater importance in the light of current public health trends, he noted. Vitamin D levels in many populations are decreasing while dental caries levels in young children are increasing.

"Whether this is more than just a coincidence is open to debate," Dr. Hujoel said. "In the meantime, pregnant women or young mothers can do little harm by realizing that vitamin D is essential to their offspring’s health. Vitamin D does lead to teeth and bones that are better mineralized."

Dr. Hujoel added a note of caution: "One has to be careful with the interpretation of this systematic review," he stated. "The trials had weaknesses which could have biased the result, and most of the trial participants lived in an era that differs profoundly from today’s environment