Prescription Drugs, Celecoxib, and Indomethacin can Cause Abnormal Development of Teeth in Children

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Highlights:

• Children's anti-inflammatory medications can cause changes to their teeth' enamel
• NSAIDs like Celecoxib and Indomethacin can interfere with the development of the enamel and cause dental enamel abnormalities which are similar to the effect of tetracycline on developing teeth
• An appropriate protocol needs to be developed to regulate these over-the-counter drugs to avoid such side effects among youngsters

A study undertaken at the University of S�o Paulo (USP) in Brazil and presented in an article published in the journal Scientific Reports suggested that anti-inflammatory medicines routinely used by children may be linked to dental enamel defects (DEDs), which affect approximately 20% of children globally (1^✔).

The researchers studied the effects of celecoxib and indomethacin, two non-steroidal anti-inflammatory drugs (NSAIDs) defined by the World Health Organization (WHO) as the first steps on the analgesic ladder, alongside paracetamol.

‘With an increase of 12% in tetracycline and other NSAIDs usage, there is a 20% impact on the development of teeth among children globally.’

Dentists at FORP-Dental USP's Enamel Clinic, who research and treat the condition daily, have seen a significant increase in the number of youngsters seeking treatment for pain, white or yellow tooth spots, dental sensitivity, and fragility in recent years. Simple chewing can fracture children's teeth in some situations. All of them are hallmark indications of DEDs of the enamel hypo mineralization type, the etiology of which remains unknown.

Dental decay in the form of carious lesions arises earlier and more frequently in these patients as a result of this illness, and their restorations are less sticky and fail more frequently. According to studies, they may need to repair restorations ten times more frequently than people with healthy teeth.

Dental enamel defects (DED) are divided into two types: qualitative and quantitative. Qualitative defects are those that are defined by hypomineralization of the enamel, where it stays at normal thickness but with faulty enamel mineralization, as seen by diffuse or delimited white to yellow-brown opacities. Quantitative defects, on the other hand, are characterized by enamel hypoplasia, which is characterized by a decrease in enamel thickness (2^✔).

The Effects of Celecoxib and Indomethacin on Tooth Development

The researchers were especially intrigued by a coincidence: the patients' ages. The initial years of life, when DEDs occur, are characterized by recurrent sickness, typically with a high fever. "These diseases are typically treated with NSAIDs, which inhibit the activity of cyclooxygenase [COX, a key inflammatory enzyme] and reduce the production of prostaglandin [which also promotes inflammation]," said Francisco de Paula-Silva, the article's last author and a professor in FORP-Pediatric USP's Department. "However, because COX and prostaglandin are known to be physiological for dental enamel, we questioned if these medicines interfered with its regular synthesis."

The researchers studied the problem using rats, since these animals have incisors that grow continually, making analysis easier. After 28 days of celecoxib and indomethacin treatment, virtually no alterations in the rats' teeth were discernible to the naked eye. When the researchers began extracting the teeth, they discovered that they cracked more easily.

Imaging and chemical composition analysis revealed that dental mineralization had been harmed. The teeth have low mineral density and low quantities of calcium and phosphate, both of which are necessary for the production of dental enamel.

When the researchers investigated the causes, they discovered changes in proteins essential for mineralization and cellular differentiation, indicating that the medications had altered the composition of the tooth 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. Hitherto we've been totally in the dark," said Paula-Silva. "We only achieved these important findings thanks to the efforts of FORP-USP's Dental Enamel Clinic and collaboration with L�cia Helena Faccioli, a professor at FCFRP-USP. She made a significant contribution to our understanding of the role of lipidic mediators in inflammatory diseases of the teeth."

The group intends to conduct a clinical trial to confirm the findings of the animal model 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. 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 the future," said Paula Silva, who compared the scenario to that of tetracycline, an antibiotic that is not advised for youngsters due to tooth discoloration.

Another crucial issue to address is the indiscriminate use of over-the-counter medications, which appears to have worsened as pediatric treatment has become more widespread, but precise data on this is lacking.

References:

1. Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs - (https:www.nature.com/articles/s41598-022-19583-w)
2. Prevalence and Diagnosis of Molar-Incisor-Hypomineralisation (MIH): A systematic review - (https:link.springer.com/article/10.1007/BF03262714)

Source: Medindia

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