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What Are The Appropriate Guidelines For Fluoride Intake?

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The appropriate use of fluoride has transformed oral health over the past 70 years, in part due to the guidelines created for fluoride intake. Recently, researchers are questioning these longstanding guidelines which served as advisory recommendations for decades. This issue of Advances in Dental Research, an e-Supplement to the Journal of Dental Research (JDR), presents the proceedings of a symposium at the 95th General Session of IADR in San Francisco, USA and includes reviews that critically examine the current guidelines for fluoride intake.

Since the benefits of fluoride in drinking water were first recognized, it has been accepted that fluoride is ingested and that remains the basis for automatic delivery. However, sources of ingested fluoride have changed and in parallel the prevalence and severity of dental caries and dental fluorosis have changed, leading to the idea that it is time to re-visit guidance on fluoride intake. Optimum fluoride intake should balance the prevention of dental caries with minimizing the occurrence of undesirable dental fluorosis.

“Guidelines for fluoride intake were first proposed when water was the only important source of fluoride. Now, there is a variety of ways of delivering fluoride and it was time to review these guidelines, considering current knowledge of the balance of benefit and risk,” said guest editor Andrew Rugg-Gunn, Newcastle University, UK and the Borrow Foundation.

“Experts from around the world gave reassurance that the current optimum range of fluoride intake is soundly based and that there is good evidence for raising the upper limit of fluoride intake. With the increase in the use of fluoride for preventing caries in adults, different guidance should be given for fluoride intake in adults compared with infants and young children.”

“While changes to current guidance on adequate intake and upper limit of fluoride intake have not been settled, it was agreed that there are strong grounds for reconsidering current guidelines,” said IADR President Angus William G. Walls, University of Edinburgh, who also contributed to this issue.

“Further research and international discussion is needed to answer the question posed by the title of this symposium.”

Importantly, the symposium prioritized the following research gaps:

  • What level of dental fluorosis is acceptable to populations globally given the benefit of caries reduction?
  • What is the best method for measuring total fluoride intake and exposure?
  • What is the best way to estimate total fluoride intake in children from birth to 3 to 4 y of age exposed to fluoridated or non-fluoridated water or fluoridated salt?
  • What is the best method to evaluate the patterns of fluid intake of children across different zones with different outdoor air temperatures?
  • Do we need periodical analyses of fluoride concentrations in infant formula, bottled water, and infant foods?
  • Do we need to validate biomarkers of exposure to fluoride?
  • What is the effect of different types of exercise on the metabolism of fluoride?
  • What is the relationship between gene polymorphisms and enamel fluorosis?
  • What is the relationship between malnutrition and enamel fluorosis?
  • Is supplementation with calcium helpful to reduce enamel fluorosis?
  • What are the pre-eruptive effects of fluoride on caries progression into dentin?
  • What is the efficacy of low-fluoride toothpastes whose formulations have been modified to increase the anticaries efficacy?

These reviews, as well as the summary of the discussion during the symposium, are included in this issue of Advances in Dental Research, an E-supplement to the Journal of Dental Research.

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Regrowing Dental Tissue With Stem Cells From Baby Teeth

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Sometimes kids trip and fall, and their teeth take the hit. Nearly half of children suffer some injury to a tooth during childhood. When that trauma affects an immature permanent tooth, it can hinder blood supply and root development, resulting in what is essentially a “dead” tooth.

Until now, the standard of care has entailed a procedure called apexification that encourages further root development, but it does not replace the lost tissue from the injury and, even in a best-case scenario, causes root development to proceed abnormally.

New results of a clinical trial, jointly led by Songtao Shi of the University of Pennsylvania and Yan Jin, Kun Xuan, and Bei Li of the Fourth Military Medicine University in Xi’an, China, suggest that there is a more promising path for children with these types of injuries: Using stem cells extracted from the patient’s baby teeth. The work was published in the journal Science Translational Medicine.

“This treatment gives patients sensation back in their teeth. If you give them a warm or cold stimulation, they can feel it; they have living teeth again,” says Shi, professor and chair in the Department of Anatomy and Cell Biology in Penn’s School of Dental Medicine.

“So far we have follow-up data for two, two and a half, even three years and have shown it’s a safe and effective therapy.”

Shi has been working for a decade to test the possibilities of dental stem cells after discovering them in his daughter’s baby tooth. He and colleagues have learned more about how these dental stem cells, officially called human deciduous pulp stem cells (hDPSC), work and how they could be safely employed to regrow dental tissue, known as pulp.

The Phase I trial, conducted in China, which has a research track for clinical trials, enrolled 40 children who had each injured one of their permanent incisors and still had baby teeth. Thirty were assigned to hDPSC treatment and 10 to the control treatment, apexification.

Those that received hDPSC treatment had tissue extracted from a healthy baby tooth. The stem cells from this pulp were allowed to reproduce in a laboratory culture, and the resulting cells were implanted into the injured tooth.

Upon follow-up, the researchers found that patients who received hDPSCs had more signs than the control group of healthy root development and thicker dentin, the hard part of a tooth beneath the enamel. Blood flow increased as well.

At the time the patients were initially seen, all had little sensation in the tissue of their injured teeth. A year following the procedure, only those who received hDPSCs had regained some sensation. Examining a variety of immune-system components, the team found no evidence of safety concerns.

As further support of the treatment’s efficacy, the researchers had the opportunity to directly examine the tissue of a treated tooth when the patient reinjured it and had to have it extracted. They found that the implanted stem cells regenerated different components of dental pulp, including the cells that produce dentin, connective tissue, and blood vessels.

“For me the results are very exciting,” Shi says.

“To see something we discovered take a step forward to potentially become a routine therapy in the clinic is gratifying.”

It is, however, just a first step. While using a patient’s own stem cells reduces the chances of immune rejection, it’s not possible in adult patients who have lost all of their baby teeth. Shi and colleagues are beginning to test the use of allogenic stem cells, or cells donated from another person, to regenerate dental tissue in adults. They are also hoping to secure FDA approval to conduct clinical trials using hDPSCs in the United States.

Eventually, they see even broader applications of hDPSCs for treating systemic disease, such as lupus, which Shi has worked on before.

“We’re really eager to see what we can do in the dental field,” Shi says, “and then building on that to open up channels for systemic disease therapy.”

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Antibiotics Destroy ‘Good Bacteria’ And Worsen Oral Infection

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New research shows that the body’s own microbes are effective in maintaining immune cells and killing certain oral infections.

A team of Case Western Reserve University researchers found that antibiotics actually kill the “good” bacteria keeping infection and inflammation at bay.

Scientists have long known that overuse of antibiotics can do more harm than good. For example, overuse can cause antibiotic resistance. But research into this phenomenon in oral health was uncharted territory.

Pushpa Pandiyan, an assistant professor of biological sciences in the School of Dental Medicine, led a team of researchers to examine “resident” bacteria, their fatty acids and their effect on certain types of white blood cells that combat infections in the mouth.

Specifically, researchers looked at the “short-term maintenance” of Tregs and Th-17 cells in fighting fungal infections, such as Candida, in a laboratory setting.

They found that those natural defenses were very effective in reducing infection and unwanted inflammation — and antibiotics can prevent such natural defenses. Their work was recently published in Frontiers in Microbiology.

“We set out to find out what happens when you don’t have bacteria to fight a fungal infection,” Pandiyan said.

“What we found was that antibiotics can kill short-chain fatty acids produced by body’s own good bacteria.”

“We have good bacteria doing good work every day, why kill them?” Pandiyan added.

“As is the case with many infections, if you leave them alone, they will leave on their own.”

“Of course, antibiotics are still needed for life threatening infections. No question about that. Our bodies have many natural defenses that we shouldn’t meddle with,” she said.

However, needless overuse of antibiotics is not helpful, she said.

“Also, we know there is a definite link between oral health and overall health,” she added.

Pandiyan said the study could have broader implications on protective effects of “resident microbiota” in other types of infections.

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New Findings On Chronic Pain Syndrome In The Mouth

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The picture is becoming clearer regarding the chronic oral pain condition known as Burning Mouth Syndrome, or BMS, which mainly affects women who are middle-aged and older. In a dissertation at Sahlgrenska Academy, additional steps are being taken toward better diagnosis and treatment.

“Our hope is that the new findings will contribute to the development of objective diagnostic criteria and effective individualized treatment both that are currently lacking,” says Shikha Acharya, who has a PhD in oral microbiology and immunology at the Institute of Odontology.

Burning Mouth Syndrome (BMS) is a chronic pain syndrome in the oral cavity that affects approximately 4% of the Swedish population. This chronic condition mainly affects middle-aged and elderly women.

The pain is experienced as burning or stinging. The tongue is most often afflicted, but the palate, lips and gums also may be affected. Other common symptoms include dry mouth and altered taste sensation, such as a bitter or metallic taste in the mouth.

BMS is a challenge for health care providers, particularly in dental care, and a debilitating condition for many of the patients. When they estimate their problem on a visual analogue scale (VAS) where 0 is “not at all difficult” and 100 is “unbearable,” the average response is 66, the dissertation indicates. The findings came from 56 women with BMS.

In her work Shikha Acharya also connected clinical findings and self-reported reported findings from questionnaires from patients with BMS about their symptoms and background (other diseases, use of medications, etc.) along with saliva-related factors. The results have been compared with a gender- and age-matched control group.

It turns out that 45 percent of the BMS patients reported to have altered taste sensations. A total of 73 percent experienced pain that was burning or stinging or a combination of the two, but stinging and numbness also occurred.

In addition to BMS, they have a higher incidence of other types of diseases, use more medications, are more prone to grinding their teeth and report more allergies than the control group. However, more advanced analyses show that BMS was strongly associated to self-reported skin diseases and subjective oral dryness.

The fact that the BMS patients, compared with people in the control group, report that they suffer considerably more from skin diseases and skin problems is a new discovery. Similarly, that the mucin proteins in BMS patients’ saliva are altered and contain lower amounts of carbohydrate structures that affect the oral cavity’s immune system.

Analysis of inflammatory constituents in saliva shows complex relationship between BMS and background inflammation, with some of the BMS patients having higher levels of inflammation than the control group while others had lower.

The dissertation work is part of a larger project aimed at finding a model for BMS that can facilitate diagnosis and treatment in the future. The new pieces of the puzzle are helping to characterize the disease and the persistent mouth pain associated with it.

“It’s important because the afflicted patients often feel that their surroundings and health care professionals doubt their ailment,” says Shikha.

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