The current study demonstrates that (1) hypercalcemia, contributes to the early lethality of CaR–deficient mice, (2) defects in endochondral bone formation in CaR–deficient mice result from effects of the excess elevations in calcium and the decrease in phosphorus and PTHrP levels, while (3) the increased osteoblastic bone formation results from direct effects of PTH. This evidence concerns the gene PTH and hypercalcemia disease.