07 February 2023

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Anti-inflammatories, cause of serious alterations of tooth enamel in children

Paola Omini

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A study conducted at the University of São Paulo (USP) (Brazil), and published in the journal Scientific Reports in September 2022, shows that anti-inflammatories commonly taken by children may be associated with tooth enamel defects (DED), which are currently observed in about 20% of children worldwide.

The authors, affiliated with the Ribeirão Preto School of Dentistry (FORP-USP) and the School of Pharmaceutical Sciences (FCFRP-USP), investigated the effects of celecoxib and indomethacin, nonsteroidal anti-inflammatory drugs (NSAIDs) classified by the World Health Organization (WHO) as the first step of the analgesic scale, along with paracetamol.

In recent years, dentists at the FORP-USP Dental Enamel Clinic, who investigate and treat the problem on a daily basis, have observed a sharp increase in the number of children seeking treatment for pain, white or yellow spots on their teeth, and tooth sensitivity and fragility. In some cases, simple chewing can fracture children's teeth. These are all classic symptoms of DED of the type known as enamel hypomineralization, the causes of which are poorly understood.

As a consequence of this disorder, dental caries in the form of carious lesions appears earlier and more frequently in these patients, whose restorations are less adhesive and tend to fail more. Studies have shown that they may have to replace restorations ten times more often throughout their lifetime than people with healthy teeth.

Research process

The researchers used rats to study the problem, as these animals have incisors that grow continuously, making analysis easier. The rats were treated with celecoxib and indomethacin for 28 days, after which there were virtually no differences with the naked eye in their teeth. However, when the researchers began to extract them, they found that the teeth fractured more easily.

Analyses based on images and chemical composition suggested that dental mineralization had been affected. The teeth contained lower-than-normal levels of calcium and phosphate, which are important for tooth enamel formation, and mineral density was low.

When the researchers looked for the reasons, they found alterations in proteins necessary for mineralization and cell differentiation, which showed that the drugs had indeed affected the composition of tooth enamel.

Next steps

"Right now, the study offers us at least one clue as to the identity of a new actor who may be involved in the development of DEDs. Until now we were totally in the dark," says Paula-Silva, professor in the Department of Pediatrics at FORP-USP and last author of the article. "We have only achieved these important findings thanks to the efforts of the Dental Enamel Clinic of FORP-USP and the collaboration with Lúcia Helena Faccioli, professor at FCFRP-USP. She made a crucial contribution to our understanding of the role played by lipid mediators related to inflammatory diseases affecting teeth."

The group plans to conduct a clinical study with the aim of confirming the results of the research in the animal model. "We will analyze the medical history of children with DED and their use of these drugs, and we will launch a clinical study that will correlate the two datasets to see if the same thing happens in humans. If so, we can make recommendations on which drugs should not be used according to which patients. We can also help develop an appropriate treatment protocol in the future," explains Paula-Silva, comparing this situation with that of tetracycline, an antibiotic not recommended for children because it causes tooth discoloration.

Another important point to be addressed is the indiscriminate use of over-the-counter medicines, a problem that appears to have worsened as paediatric care has become more widespread, although no specific information is yet available.

Juliana de Lima Gonçalves et al. "Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs." Scientific Reports. 12, Article number: 15823 (2022). https://doi.org/10.1038/s41598-022-19583-w