Anti-inflammatory drugs would cause alterations of the dental enamel

Anti-inflammatory drugs would cause alterations of the dental enamel.


A study conducted at the University of São Paulo (USP) in Brazil, and described in an article published in the journal Scientific Reports, demonstrates that anti-inflammatory drugs commonly taken by children may be associated with dental enamel defects, currently present in around the 20% of the world’s children. The authors, affiliated with the Ribeirão Preto School of Dentistry (FORP-USP) and the School of Pharmaceutical Sciences, studied the effects of celecoxib and indomethacin, non-steroidal anti-inflammatory drugs (NSAIDs) classified by the World Health Organization (WHO) as the first step on the analgesic ladder, along with paracetamol. In recent years, the dentists of the FORP-USP Dental Enamel Clinic, who study and deal with the problem on a daily basis, have observed a sharp increase in the number of children who seek treatment for pain, white or yellow spots on the teeth, sensitivity and dental fragility. In some cases, simply chewing can fracture teeth. All of these are classic symptoms of dental enamel defects 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. The first years of life, when dental enamel is forming, is a time when illnesses are frequent, often with high fever. “These diseases are typically treated with NSAIDs, which inhibit cyclooxygenase activity(COX, an inflammatory enzyme) and reduce the production of prostaglandins (which also promote inflammation),” said Francisco de Paula-Silva, professor in the Department of Pediatrics at FORP-USP and author of the paper. “However, COX and prostaglandins are known to be physiological for dental enamel and we therefore wondered whether these drugs interfere in the normal formation of this structure.”

To study the problem, the researchers used rats, which have continuously growing incisors, which facilitates the analysis. The rats were treated with celecoxib and indomethacin for 28 days, after which virtually no differences were visible to the naked eye in their teeth. However, when the researchers began extracting the teeth, they found that they fractured more easily. The teeth contained subnormal levels of calcium and phosphate, which are important for the formation of dental enamel, and the mineral density was low. When the researchers looked for the reasons for this situation, they found alterations in the necessary proteins for mineralization and cell differentiation, demonstrating that the drugs had indeed influenced the composition of the tooth enamel.

The next steps

“At the moment, the study offers us at least a hint as to the identity of a new actor who may be involved in the development of dental enamel defects. Until now we were completely in the dark,” said Paula-Silva. 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 affected by this dental problem and the use of these drugs, and we will organize a clinical study that will relate the two data sets in order to be able to make recommendations on which drugs should not be used and for which patients. We can also help define an appropriate treatment protocol in the future,” Paula-Silva said, comparing this situation to that of thetetracycline , an antibiotic not recommended for children because it causes tooth discoloration.





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