In summary, the phenotype of Fgf-23−/−/NaPi2a−/− compound mutants demonstrates that 1) increased NaPi2a activity is the main cause for the severe hyperphosphatemia observed in Fgf-23−/− mice, 2) that the mineralization defect and the growth plate changes in Fgf-23−/− and Fgf-23−/−/NaPi2a−/− compound mutants at 6 weeks of age are partly due to lack of Fgf-23 function rather than systemic phosphate homeostasis, and 3) that the altered expression of the sibling proteins OPN and DMP1 in bone is independent of serum phosphate levels in mice ablated for Fgf-23. Here, DMP1 is linked to hyperphosphatemia.