FGF23 increases induced by vitamin D metabolites are enhanced by increasing the serum calcium. Comparison of the FGF23 responses to exogenous 1,25(OH)2D and 25(OH)D treatment of WT mice (A) and of 1(OH)ase−/−C mice (on a high-Ca diet) and 1(OH)ase−/−R mice (on a rescue diet) (B). Serum Ca levels are shown in WT mice (C) and in 1(OH)ase−/−C and 1(OH)ase−/−R mice (D) after treatment with 1,25(OH)2D and 25(OH)D. Intraperitoneal injections of 1,25(OH)2D (6 ng/g) or 25(OH)D (100 ng/g) were given every 2 days for 1 week. Alternatively, exogenous 1,25(OH)2D (50 pg/g) was administered for 2 months (2M) to 1(OH)ase−/−C mice (on a high-Ca diet). Bars represent the mean±SEM. Significant differences between groups were determined by one-way ANOVA followed by Bonferroni test. *P≤0.05; **P≤0.01; ***P≤0.001; and ****P≤0.0001 compared with vehicle-treated mice of the same genotype on the same diet; ‡P≤0.05 compared with 1(OH)ase−/−C mice.