Mechanistically, UD inhibited phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) phosphorylation, facilitated Forkhead box O (FoxO) nuclear translocation, and suppressed reactive oxygen species (ROS) accumulation, thereby preventing NFATc1 activation and nuclear import.<h4>Conclusion</h4>Collectively, this research identifies a novel metabolic-signaling interplay linking pyrimidine metabolism with osteoclast differentiation and highlights UD as a promising metabolic regulator for the treatment and prevention of osteoporosis. The gene discussed is NFATC1; the disease is osteoporosis.