We found that FR167653 not only blocked osteoclast differentiation induced both by PTHrP and sRANKL with down regulation of c-Fos and NFATc1 in bone marrow macrophages without affecting RANKL and OPG expression in bone marrow stromal cells, but also alleviated bone resorption induced by PTHrP with partial reduction of hypercalcemia in vivo. Here, TNFRSF11B is linked to hypercalcemia disease.