This FAERS-based study identified multiple drug classes associated with OP/OPN-related adverse event signals, with anti-viral drugs - particularly tenofovir disoproxil and its combination therapies - exhibiting the strongest signal. Although glucocorticoids had a lower reporting proportion, their short onset time underscores the need for vigilance. These findings provide real-world evidence for drug safety management and highlight the necessity of bone health monitoring in long-term medication users. Future studies should integrate clinical data to validate these findings and explore underlying mechanisms.