Use of anti-inflammatory drugs by children may be associated with dental enamel defects

A study conducted at the University of São Paulo (USP) in Brazil shows that anti-inflammatory drugs commonly taken by children may be associated with dental enamel defects (DEDs).

Dental researchers affiliated with the Ribeirão Preto Dental School (FORP-USP) and School of Pharmaceutical Sciences (FCFRP-USP) conducted the study that was published in the journal Scientific Reports.

The authors investigated the effects of celecoxib and indomethacin, non-steroidal anti-inflammatory drugs (NSAIDs).

Classified by the World Health Organization (WHO) alongside paracetamol as pain relief medication, these NSAIDS are commonly prescribed for young patients.

Dentists at FORP-USP’s Dental Enamel Clinic noted a significant increase in the number of children seeking treatment for pain, white or yellow tooth spots, and dental sensitivity and fragility. The clinicians found these symptoms consistent with a type of DEDs known as enamel hypomineralization, which causes are poorly understood.

DEDs lead to dental failures and adhesion problems

Patients suffering from this disorder are more prone to dental decay in the form of carious lesions. They also tend to experience more dental failures and bonding issues with their restorations. Studies indicate that such patients replace restorations ten times more often over a lifetime than people with healthy teeth.

The researchers found that DEDs tend to occur in patients during their formative years, marked by frequent bouts of sickness, typically with high fever.

“These diseases are typically treated with NSAIDs, which inhibit the activity of cyclooxygenase (COX, a key inflammatory enzyme) and reduce production of prostaglandin [which also promotes inflammation],” said Prof Francisco de Paula-Silva, a professor in FORP-USP’s Pediatric Department and co-author of the article.

“However, COX and prostaglandin are known to be physiological for dental enamel, and we therefore wondered whether these drugs interfered in the normal formation of this structure.”

NSAIDs affect composition of dental enamel

The researchers used rats in their study, treating the animals with celecoxib and indomethacin for 28 days. While no visible difference was observed after the period, the researchers found that the teeth fractured more easily when they began extracting.

Upon closer examination based on imaging and chemical composition, they found the teeth contained sub-normal levels of calcium and phosphate, along with low mineral density – which are important to dental enamel formation.

They also discovered alterations in proteins required for mineralization and cellular differentiation. This suggests that the NSAIDs have indeed affected the composition of the dental enamel.

“Right now, the study at least offers us a clue to the identity of a new player that may be involved in the development of DEDs,” said Prof Paula-Silva.

“Hitherto we’ve been totally in the dark. We only achieved these important findings thanks to the efforts of FORP-USP’s Dental Enamel Clinic and collaboration with Lúcia Helena Faccioli, a professor at FCFRP-USP.

“She made a crucial contribution to our understanding of the role played by lipidic mediators related to inflammatory diseases that affect teeth.”

Next steps

The research team plans to conduct a clinical study to confirm the results of the animal-tested research.

“We’re going to analyze the medical history of the children with DEDs and their use of these drugs, and we’ll set up a clinical study that will correlate the two datasets to see if the same thing happens to humans,” said Prof Paula-Silva.

“If so, we can make recommendations on which drugs shouldn’t be used for which patients. We can also help work out an appropriate treatment protocol in future.”

Read the article: Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs.