Escitalopram exposure compromises osteogenic potential of human osteoblastic cells

Objective: This study aimed to assess the impact of escitalopram on bone metabolism by evaluating its effects on cell viability and proliferation, wound-healing capacity, osteogenic activity, bone formation markers, and collagen deposition. Design: The effects of escitalopram were studied on human osteoblastic SAOS-2 cells. Escitalopram (1–1000 µM) was tested in a dose–response curve. Cell viability was measured by MTT assay, and proliferation by hemocytometer counting. Cell migration was examined with the Scratch assay over 72 h. Osteogenic differentiation was assessed by gene expression of RUNX2, Osterix (Osx), bone sialoprotein (BSP), type I collagen (COL1), and osteocalcin (OCN) using RT-qPCR. Alkaline phosphatase (ALP) activity was analyzed at 4 and 8 days. Mineralization was determined by Alizarin Red staining (days 10, 14, 21). For last, Immunofluorescence was carried out for collagen 1 staining (days 3, 7 and 10). Results: Escitalopram induced cytotoxicity in doses greater than 100 µM, reducing cell viability within 24 h. At non-toxic concentrations (≤30 µM), proliferation was enhanced in 30 µM after 7 days. Conversely, escilalopram reduced the migration capacity in a concentration-dependent manner. Moreover, the gene expression of RUNX2, OSX, BSP, COL1, and OCN were diminished when exposed to escitalopram. In the functional tests, escitalopram significantly decreases ALP activity at day 4, but not at day 8. Mineralization was dose-dependently impaired at 14 and 21 days. Collagen type I immunofluorescence exhibit weaker staining when escitalopram exposure. Conclusion: Escitalopram compromises osteoblast differentiation, extracellular matrix formation, and migratory potential. These results provide mechanistic insight into the adverse skeletal effects of SSRIs and suggest the need for monitoring bone health in long-term users.