Moreover, we found that raising the intracellular level of calcium in BMSCs by treatment with ionomycin rescues the osteoporotic phenotype in alpl+/− mice and BMSC-specific (Prrx1-alpl−/−) conditional alpl knockout mice, and the treatment restores stem cell function of BMSCs from HPP patients, suggesting a new strategy for HPP therapy. Here, PRRX1 is linked to hypophosphatasia.