Niclosamide Suppresses Osteoclastogenesis and Bone Resorption: Involvement of STAT3 Signaling

Niclosamide, known for its anticancer and anti-inflammatory effects via modulation of NF-κB and STAT3 signaling, has now been shown to suppress osteoclast differentiation and function through STAT3 inhibition. In vitro experiments demonstrated that niclosamide downregulates STAT3 activation, leading to reduced expression of genes involved in osteoclast differentiation, acid secretion, chemotaxis, and pyroptosis, thereby impairing multiple osteoclast biological behaviors. In vivo, niclosamide treatment attenuated bone loss in an ovariectomy-induced mouse model of osteoporosis by inhibiting osteoclast activity. The STAT3 activator colivelin partially reversed these niclosamide-induced effects on bone metabolism. Collectively, niclosamide inhibits both osteoclast formation and the bone-resorptive function of mature osteoclasts via suppression of the STAT3 pathway, suggesting a novel therapeutic approach for osteoporosis.