Drug Repositioning Based on Single-Cell Transcriptomics Data Identifies Quinidine as a Potential Drug for Treating Osteoporosis

Osteoporosis (OP) is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, but no effective clinical therapies exist. To address this unmet need, we employed a computational pipeline drug repositioning method based on single-cell data and Mendelian randomization analysis to screen potential candidate drugs for the treatment of osteoporosis. Quinidine was identified as a potential therapeutic agent for osteoporosis. Mendelian Randomization analysis indicated a causal relationship between Quinidine's drug target SCN5A and osteoporosis. Larval zebrafish experiments confirmed that Quinidine can ameliorate the Dexamethasone-induced osteoporosis model and promote cranial bone mineralization. qPCR showed that Quinidine can promote osteoblast-related gene expression and inhibit osteoclast-related genes expression. This study systematically revealed Quinidine as a potential drug in the prevention and treatment of osteoporosis through an integrated strategy of single-cell drug repositioning, genetic causal inference, and animal model validation.