In this study we compare the effect of the dietary Pi content, particularly Pi-restriction, in wild type (WT) and intestinal-specific NaPi-IIb deficient mice (NaPi-IIb−/−) and show that upon Pi-restriction NaPi-IIb−/− mice demineralize bone which may help to prevent more severe hypophosphatemia. The gene discussed is SLC34A2; the disease is hypophosphatemia.