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REACT (Real-world Emulated Clinical Trials): A Framework for DrugRepurposing Applied to Osteoporotic Fractures

Liu, J.; Lee, S.; Chen, X.; Fernandez, S.; Wu, Q.; Zhang, P.

2026-03-23 pharmacology and therapeutics
10.64898/2026.03.20.26348832 medRxiv
Show abstract

Osteoporotic fractures remain common despite available therapies, highlighting the need for new, safe, and affordable treatment options. Advances in real-world data and causal inference have enabled target trial emulation, with prior frameworks demonstrating drug repurposing using observational data. However, no large-scale trial emulation framework has been applied to systematic drug repurposing for osteoporotic fracture prevention. To address this gap, we developed REACT (Real-world Emulated Clinical Trials), a scalable framework that operationalizes established target trial principles into an automated, comparator-robust pipeline for high-throughput drug screening. Applied to fracture prevention in older adults with osteoporosis, REACT screened 1,222 drugs and identified 18 with statistically significant associations, including 11 with protective effects and 7 with risk-increasing effects. The convergence of these findings with biological and prior observational evidence underscores REACTs ability to surface clinically meaningful patterns and its potential as a generalizable platform for accelerating real-world drug discovery and safety surveillance.

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