Innovative Nutritional Prevention of Osteoporosis: the Polyphenol Fisetin Sustains Bone Health by Controlling Osteoblasts and Osteoclasts Differentiation

Osteoporosis is marked by reduced bone mass and increased fracture risk. This study assesses the preventive effects of fisetin, a plant-derived polyphenol, in two murine models of estrogen deficiency and inflammation-induced bone loss. In vivo, fisetin supplementation preserved bone mineral density, improved microarchitectural parameters, and favorably modulated circulating bone markers. In vitro, fisetin promoted primary preosteoblast differentiation and activity by enhancing Runx2 transcriptional activity. Concurrently, it inhibited RANKL-induced osteoclastogenesis as shown by reduced multinucleated cell formation, TRAP activity, and expression of key osteoclast differentiation genes. These findings support fisetin as a novel nutritional strategy for osteoporosis prevention through dual regulation of bone remodeling cells.