Atypical antipsychotics olanzapine and clozapine increase bone loss in female rats with experimental periodontitis

Background and Objectives Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second‐generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases. Methods In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature‐induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro‐inflammatory cytokine TNF‐α were made. Results Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature‐induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF‐α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis. Conclusion The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.