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The New Cavity Fighters


Novel products could lead to fewer dates with the drill
Jessica Gorman

Smile wide and check out those pearly whites in the mirror. Now, look closer. The action going on behind that grin might surprise you, especially if you didn't brush after lunch.

This microradiograph shows an artificial lesion in a tooth at a depth of about 100 microns (arrow). The lesion appears dark because it contains less mineral than the denser layers above and below.


Bacteria in plaque may be munching on your leftovers right now, breaking down sugars that remain in your mouth. Acids produced in this sweet feast can slip slyly through a tooth's enamel. By dissolving minerals just below the surface, acid silently sabotages a tooth's structure.

Usually, however, a natural champion of tooth health puts up a fight: a swish of saliva full of calcium and phosphate. Saliva works to rebuild teeth in which the calcium phosphate has begun to dissolve. Thus the dynamic process of demineralization and remineralization marches on.

Meanwhile, a mouth's owner remains blissfully unaware of the assaults and counterassaults, unless the acid actually carves out a cavity that needs a dental drill.

Still smiling?

Actually, there's reason to be. For nearly a century, dentistry has aimed to prevent or reverse tooth decay, or dental caries, before a drill becomes necessary. Now, decades of research into cavity formation have finally started to produce products that go beyond traditional treatments, such as the familiar fluoride toothpaste. Novel chewing gum, toothpastes, or mouth rinses take advantage of complicated techniques to add back the minerals that acid has chewed away. The first of these remineralizing treatments are already in drugstores and dentist offices, and researchers are testing still more on human teeth in the lab.

"Think of medicine and go back to the days when if you had TB in the lung, then you cut out the lung," says John D. B. Featherstone, head of the new department of preventive and restorative dental sciences at the University of California, San Francisco. "But now, it's treated by antibiotics. We're way back in the dark ages in dentistry in terms of prevention and therapeutics."

Improved hygiene

Dental hygiene improved dramatically in the last century, no doubt. In the 1930s, scientists observed that residents drinking water from public supplies that naturally contained fluoride developed fewer cavities. After clinical trials confirmed this link, deliberate fluoridation of community water flourished.

Fluoride, the scientists realized, encourages the calcium and phosphate in saliva to remineralize teeth. It replaces hydroxyl ions in the natural calcium phosphate compound, called hydroxyapatite, that makes up teeth. The substitution converts it to the more acid-resistant fluorapatite. Over time, people began seeking even greater protection by using fluoridated toothpastes and mouth rinses.

In the 1950s and 1960s, researchers found that bacteria cause tooth decay and periodontal diseases, which led to a new line of research in prevention and treatment.


Usually, saliva replaces calcium phosphate in a tooth at the rate it dissolves. Under cavity-forming conditions, however, acids in plaque dissolve the mineral more quickly than the saliva can replace it. Therapies that add fluoride, calcium, and phosphate encourage remineralization to proceed faster than mineral loss.


"At the turn of the last century, most Americans could expect to lose their teeth by middle age," Surgeon General David Satcher said in the first surgeon general's report on oral health, released in May. Today, in contrast, "most middle-aged and younger Americans expect to retain their natural teeth over their lifetime and do not expect to have any serious oral health problems," the report says.

Despite the century's dental successes, there's still plenty of cavities to keep a dentist's drill busy. The surgeon general's study reports that more than 50 percent of children ages 5 to 9 and 78 percent of 17-year-olds have at least one cavity or filling. In the United States, more than 108 million people don't have dental insurance, and 100 million—more than one-third of the population—live in communities without fluoridated water supplies.

The report also points to a disparity in who suffers: "What amounts to 'a silent epidemic' of oral diseases is affecting our most vulnerable citizens—poor children, the elderly, and many members of racial and ethnic minority groups," it says.

Improving on saliva

In the 1980s, several groups of researchers began developing mouth rinses and toothpastes that would provide calcium and phosphate, as well as fluoride, to improve on saliva's natural remineralizing power (SN: 4/19/86, p. 251). One of the scientists' primary concerns was creating remineralization products to help people at high risk of developing tooth decay because they have low saliva production. This condition can result from various medicines, radiation treatment, chemotherapy, and certain diseases.


Dentists might one day place sticky, moldable wedges between teeth in which an X ray reveals the shadow of a cavity. As the wedges dissolve, they release fluoride, calcium, and phosphate directly to the region that needs repair.


Some scientists also suspected that by speeding up remineralization, the calcium-phosphate mouth rinses and toothpastes might benefit just about anyone. One day, they predicted, over-the-counter and dentist-office treatments could prevent or repair early tooth decay, maybe even before the patient knows about a potential cavity.

That day turned out to be surprisingly distant.

"We had a pretty good understanding of how saliva remineralized teeth," says Frederick C. Eichmiller, director of the American Dental Association Health Foundation's Paffenbarger Research Center in Gaithersburg, Md. "What we hadn't put together at that time was how we could take synthesized materials or environmental calcium phosphate and add them as active ingredients and speed up the process."

One of the challenges of remineralizing teeth with calcium and phosphate was getting a soluble form of these minerals through a tooth's surface enamel so they can work where an early cavity is forming. If the ions of calcium and phosphate combine before diffusing into teeth, the resulting calcium phosphate quickly crystallizes and can't penetrate the enamel.

Chemists also needed to figure out how to dispense calcium, phosphate, and fluoride gradually. Toothbrushing and mouth rinsing last for maybe a minute, but bacteria soon start in again on missed food particles or new snacks. Researchers have created formulations that slowly disperse fluoride or minerals, sometimes continuing after an application ends. Some examples are chewing gum or sticky substances, resembling hard candy, that a dentist applies between the teeth. Moreover, when a person chews gum, salivary flow increases.

Remineralizing for kids

One remineralizing application is already available to the masses. It's found in the chewing gums Trident Advantage and Trident for Kids, which Warner-Lambert, now part of Pfizer, launched in October 1999.

The formula for these gums and many other new products in the pipeline includes calcium and phosphate. But strategies for getting these minerals under the tooth surface differ from one product to the next.

"The paradox here is that you want to supply [soluble] calcium and phosphate to produce insoluble bones and teeth," says Eric C. Reynolds at the University of Melbourne in Australia, who developed Trident's gums. Newborns need a large supply of calcium and phosphate for their quickly growing bones, he says. "So, we just looked at nature, and milk has the answer," he says. "Nature's evolved this system in milk to carry very high levels of calcium and phosphate in a highly bioavailable form" to the gut.

Reynolds and his colleagues used a milk protein called casein. Its peptides stabilize a soluble form of calcium phosphate before it crystallizes. The peptides also seem to deliver the calcium phosphate to the tooth surface. Known commercially as Recaldent, the microscopic particles of casein-peptide-stabilized calcium phosphate diffuse through the surface of teeth to become crystalline hydroxyapatite where cavities have begun.

"With the Recaldent gum, you get substantial remineralization right through the body of the lesion," says Reynolds.

"The gum turned out to be even better than we'd hoped," he adds. Three hours after chewing the gum, volunteers still had Recaldent in plaque removed from their teeth, he reports.

Reynolds is now beginning a 3-year test to determine whether the gum reduces tooth decay. In Melbourne, Australia, 3,000 schoolchildren will chew the gum twice a day.

Toothpaste, too

Enamelon toothpaste has also reached consumers' mouths. It's made it into the arena of the big toothpastes, sitting on the drugstore shelf near a dozen types of similarly priced Crest and Colgate tubes. Yet it may have trouble holding its ground. According to Enamelon, Inc.'s 1999 annual report, the company is losing money and prepared to file for bankruptcy.


An electron micrograph shows clusters of casein-peptide-stabilized calcium phosphate (black dots), or Recaldent, surrounding bacteria in tooth plaque.


Ironically, some of the best evidence of Enamelon's effectiveness—the toothpaste hasn't yet earned the ADA Seal of Acceptance—is emerging now.

Enamelon's founder licensed the technology in the early 1990s from the Paffenbarger Research Center, where scientists first developed this method to apply soluable calcium phosphate to teeth. Enamelon then added fluoride, incorporated the technology into a toothpaste, and created a unique dispensing tube. Enamelon's duel-chamber tube contains a white toothpaste loaded with calcium and a blue one containing phosphate and fluoride. Squeezing the tube produces side-by-side stripes.

"You have to keep the calcium separate from the fluoride and phosphorus until you actually apply it to the teeth," says Tony Winston, formerly vice president of technology and clinical research at Enamelon. "And when you do that, there are some tricks to the formulation to keep the calcium, phosphorus, and fluoride from reacting too quickly. You don't want it to precipitate out the second it gets into the mouth."

In fact, some skeptics have suggested that remineralization with this technique would occur on tooth surfaces but not below, where it's needed. New studies in people with normal saliva and others with low saliva suggest that, in fact, Enamelon promotes remineralization in teeth.

"Once we'd done the basic technology, what we then had to do was prove that the thing worked," Winston says. "We ended up with some pretty impressive clinical data that demonstrate that the product is highly effective at remineralizing teeth."

In patients receiving head and neck radiation to treat cancers—a group at high risk of poor salivary flow—Enamelon's remineralizing properties were "significantly superior" to a conventional fluoride application in preventing root decay, according to a report published in the July 1999 Gerodontology.

"We have a very high-risk population and have found that [Enamelon] does protect as compared to a flouride mouth rinse," says Athena S. Papas of Tufts University School of Dental Medicine in Boston, who led the study and has also developed some of the new commercial fluoride mouth rinses. "In people who don't have saliva, it's critical to supply the calcium and phosphate, either as a rinse or as a toothpaste, to remineralize the teeth."

Technology horizon

More remineralization technologies lie on the horizon, as well. Researchers at Paffenbarger developed a chewing gum of their own. Like Trident's, the formula for this gum includes calcium and phosphate, but the researchers use a different strategy for getting the minerals under the tooth surface.


Microradiographs of tooth lesions before and after treatment with Recaldent gum (bottom panels) show more remineralization than with an ordinary sugarfree gum (top panels).


Paffenbarger's gum contains a calcium compound and a phosphate compound that don't mix until they're moistened in the mouth, says Laurence C. Chow. "We don't want the calcium to come out all in the first minute, and we don't want too much calcium to come out," he says. "We can control this by using a calcium compound with the appropriate solubility and the particle size. Then, we do the same thing with the phosphate."

"When the gum is chewed, we can get a sustained level of release at least for 15 minutes," he reports.

A study on 14 people published in 1998 by Chow and his colleagues suggested that an earlier version of this gum prevented tooth decay after a sugar rinse more effectively than ordinary gum does. They also found that the gum deposits a reservoir of mineral in the mouth's plaque and saliva that helps defend teeth against future acid attacks. If a person chews the gum after eating sugary food, acid will attack the additional calcium phosphate pool more readily than teeth.

In another project, Paffenbarger researchers have been working to make current fluoride rinses and toothpastes more effective at aiding remineralization. In today's toothpastes, "just about 99.9 percent, perhaps, of the fluoride in the toothpaste gets spit out or rinsed out," says Chow.

"We can make this process more efficient such that we can get a significantly larger amount of fluoride deposited in the mouth without having to increase the fluoride concentration," he says.

The method involves two components: one rinse containing a fluoride salt and another one containing calcium chloride. When the two are combined just before or after entering the mouth, a calcium fluoride precipitate forms only after the calcium and floride ions have a chance to infiltrate the tooth lesions and diffuse into plaque. Later, the calcium fluoride gradually dissolves, leaving a higher concentration of fluoride in plaque and saliva.

Chow and his colleagues reported in the April Journal of Dental Research that the experimental two-rinse system remineralized teeth better than an ordinary sodium fluoride rinse containing the same concentration of fluoride. In fact, it produced a similar amount of remineralization as a sodium fluoride rinse with four times the fluoride concentration.

"A lower fluoride [concentration in toothpaste] can be quite desirable for children, where an overdose of fluoride could cause fluorosis," says Chow. This condition damages teeth and bones. "That overdose comes primarily because little kids tend to swallow toothpaste, a lot," Chow explains.

He says these products could be especially useful to people with low levels of saliva. Whether they will make it into popular use, however, will depend on people in business, not science, he says.

"They might not want to market this product," he says. "People might be more interested in the whitening [toothpastes], for example. Because of the business side of the story, we may or may not get the best product."

Wave of the future

Whether companies will want to sell, and consumers will choose to buy, the coming crop of remineralization products remains to be seen. So does the long-term effectiveness of treatments. However, preventive dentistry—rather than the drill—is more than ever the wave of the future in tooth care, according to dental researchers. Many also suggest that remineralization could work in concert with other developing preventive techniques, such as control of cavity-causing bacteria or repair of incipient cavities with lasers.

"If you go to the dentist now, he or she will identify that you have a cavity, they'll fill it, send you on your way," says Featherstone. "There's no treatment of the disease whatever."

"We've known for 20 years what to do" to prevent cavities, he says. "It's a matter of putting it into practice now. I think we've got a new future of dentistry."



References:

Chow, L.C., et al. 2000. Remineralization effects of a two-solution fluoride mouthrinse: An in situ study. Journal of Dental Research 79(April):991-995. Abstract available at http://jdr.iadrjournals.org/cgi/content/abstract/79/4/991.

Papas, A., et al. 1999. Double blind clinical trial of a remineralizing dentifrice in the prevention of caries in a radiation therapy population. Gerodontology 16(July):2.

Satcher, D. 2000. Oral Health in America: A Report of the Surgeon General. U.S. Public Health Service. Available at http://www.nidcr.nih.gov/sgr/execsumm.htm.

Vogel, G.L. . . . L.C. Chow, et al. 1998. Composition of plaque and saliva following a sucrose challenge and use of an a-tricalcium-phosphate-containing chewing gum. Journal of Dental Research 77(March):518-524. Abstract.

Further Readings:

The American Dental Association has a Web site at http://www.ada.org/.

Additional information about the National Institute of Dental and Craniofacial Research can be found at http://www.nidcr.nih.gov/.

Sources:

Laurence C. Chow
ADAHF Paffenbarger Research Center
National Institute of Standards and Technology
Gaithersburg, MD 20899

Frederick C. Eichmiller
ADAHF Paffenbarger Research Center
National Institute of Standards and Technology
Gaithersburg, MD 20899

John D.B. Featherstone
Department of Preventive and Restorative Sciences
University of California, San Francisco
707 Parnassus Avenue
Box 0758
San Francisco, CA 94143

Gary H. Hildebrandt
Moos Tower
515 Delaware Street, SE
Minneapolis, MN 55455-0348

George H. Nancollas
Chemistry Department
Natural Sciences Complex
State University of New York
Buffalo, NY 14260-3000

Athena S. Papas
School of Dental Medicine
Tufts University
One Kneeland Street
Boston, MA 02111

Eric C. Reynolds
School of Dental Science
University of Melbourne
711 Elizabeth Street
Melbourne, Victoria 3000
Australia



From Science News, Vol. 158, No. 8, Aug. 19, 2000, p. 122.

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