Excessive phosphorus intake adversely affects bone and mineral metabolism. Estrogen is one of the factors affecting fibroblast growth factor 23 (FGF23), a phosphorus-regulating hormone. However, the interaction between excess phosphorus and estrogen status has not been fully elucidated. This study investigated the involvement of estrogen in the effects of high phosphorus intake on bone metabolism and ectopic calcification in ovariectomized (OVX) rats. The interaction between high phosphorus diet and OVX was not observed in bone mineral density and aortic calcium. In contrast, high phosphorus intake markedly increased renal calcium concentration in sham rats, whereas the effect was attenuated in OVX rats, which was reversed by a selective estrogen-receptor modulator treatment. A strong positive correlation between renal calcium and serum FGF23 was observed. In addition, fibroblast growth factor receptor 1 (FGFR1: a predominant receptor of FGF23) inhibitor treatment partially decreased renal calcium concentrations in rats with high phosphorus intake. In conclusion, the effect of high phosphorus intake on bone metabolism and aortic calcification did not depend on the estrogen status; in contrast, high phosphorus intake synergistically induced nephrocalcinosis in the presence of estrogenic action on the bone. Furthermore, FGF23 was involved in the nephrocalcinosis induced by high phosphorus intake partially through FGFR1 signaling. Phosphorus is one of the nutrients that are more likely to be consumed excessively. According to the NHANES 2005-2006, the mean daily phosphorus intake exceeds the recommended dietary allowance for most age groups 1. Although the phosphorus content of Western diet is increasing because of the increasing use of phosphorus-containing food additives and increasing consumption of processed foods and soft drinks containing these additives 2 , nutrient composition tables do not usually include phosphorus from food additives 3. Therefore, dietary phosphorus intake may have been underestimated 1. Many researchers have reported the adverse effects of excess phosphorus intake. High phosphorus (HP) intake reduces bone mineral density (BMD) in rats 4-6 and adversely affects bone metabolism in humans 7. HP intake induces arterial medial calcification in animal models of chronic kidney disease (CKD) 8,9 and impairs endothelial function in humans 10. An HP diet increases renal calcium concentration and induces high incidence of nephrocalcinosis in rats 11,12. In a prospective cohort of US healthy adults, HP intake is associated with increased mortality 13. Fibroblast growth factor-23 (FGF23) is an important regulator of phosphorus homeostasis by inhibiting renal phosphorus reabsorption and decreasing intestinal phosphorus absorption through inhibiting 1,25-dihydroxyvitamin D [1,25(OH) 2 D] synthesis. Some factors affect FGF23, and one of which is estrogen. An in vitro study reported that estrogen increased mRNA expression and protein levels of FGF23 in osteoblast-like cells 14. Ovariectomy (OVX) decrease...