Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts and Osteosarcoma Cells

• Main Authors: Böker, K.O (Author), Di Fazio, P. (Author), Matziolis, G. (Author), Wagener, N. (Author)
• Format: Article
• Language: English
• Published: MDPI 2022
• Subjects: antiepileptic drugs; bone defects; human bone cells; osteoblastogenesis; pregabalin
• Online Access: View Fulltext in Publisher

 Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica®). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mes-enchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was pro-moted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregab-alin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to sys-temic effects of pregabalin. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.