• Nimbolide inhibits osteoclast differentiation and promotes apoptosis of mature osteoclasts in vitro in a concentration-dependent manner.
• Nimbolide exerts its pro-apoptotic effect on osteoclasts via the Fas/FasL signaling pathway.
• In vivo, nimbolide reduces bone loss in ovariectomized mice, an estrogen deficiency-induced osteoporosis model.
• Nimbolide does not significantly affect serum estradiol levels, suggesting a direct effect on osteoclasts rather than hormonal modulation.