Olanzapine affects bone formation via oral Enterococcus through SAA1 gene and extracellular matrix-related pathways.

Olanzapine is a commonly used drug in the treatment of schizophrenia, but the mechanism of abnormal bone metabolism caused by olanzapine is still unclear. The change of microflora may be an important factor leading to the change of bone metabolism. Therefore, the purpose of this study was to explore a plausible hypothesis that olanzapine may aggravate abnormal bone metabolism and cause bacterial imbalance in patients with schizophrenia. This study intervened in mice by gavage with olanzapine to detect changes in alveolar bone tissue and oral microbiota. The effect of related bacteria on osteogenesis was further examined. The results showed that Enterococcus increased, the bone mass and type I collagen of alveolar bone decreased. Enterococcus lipoteichoic acid (LTA) inhibited osteogenic differentiation and up-regulated SAA1 gene expression. SAA1 gene can down-regulate the expression of COL1A1 gene, and the proteins encoded by the two may interact. Olanzapine may increase the relative abundance of oral Enterococcus, whose components are plausibly linked to increased expression of SAA1 gene and inhibition of bone formation through extracellular matrix-related pathways. These exploratory findings support further exploration of microbiota-based strategies to alleviate skeletal complications and promote oral health. The clinical research presented in this paper has been registered on ClinicalTrials.gov, a platform of the U.S. National Institutes of Health (Registration Number: NCT06123897; URL: https://clinicaltrials.gov/ct2/show/NCT06123897), with the registration date of November 9, 2023.