Hirosaka Hayashi, Yutaka Miura, Yoshitaka Iwazu, Hideyuki Mukai, Yoshiyuki Mori, Takahiro Kuchimaru, Nobuhiko Ohno, Tatsuya Aiba, Risa Okada, Daisuke Kamimura, Dai Shiba, Hiroshi Kurosu, Makoto Kuro-O
Communications biology 9(1) 2026年1月22日
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that promotes urinary phosphate excretion in response to phosphate loading. While essential for phosphate homeostasis, elevated FGF23 increases phosphate concentration in the renal tubular fluid, promoting calcium-phosphate crystal formation and tubular injury. Here we show that bone resorption mobilizes phosphate into the circulation and mimics the pathophysiology of dietary phosphate loading. Enhanced bone resorption, induced by soluble receptor activator of NF-κB ligand (sRANKL) administration or microgravity exposure on the International Space Station, increased circulating FGF23 levels and caused renal tubular injury in mice. Pre-treatment with bisphosphonate, an inducer of osteoclast apoptosis, prevented sRANKL-induced increases in FGF23 and tubular damage. These findings suggest that bone mineral loss may contribute to renal tubular injury in clinical settings, including immobilization, osteoporosis, and chronic kidney disease-mineral bone disorder.