Emerging roles for calcium-regulating hormones beyond osteolysis

Parathyroid hormone (PTH), the active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and PTH-related peptide (PTHrP), the mediator of hypercalcemia of malignancy, are all osteolytic hormones. Recent studies have demonstrated that endogenous PTH and PTHrP also exert bone anabolic activity and that PTHrP is a crucial modulator of growth plate development. At least part of these PTHrP functions can be mediated by intracrine effects, involving a unique interplay of cell surface membrane and intracellular signaling. 1,25(OH)2D also exerts bone anabolic effects and, as with PTHrP, acts on multiple extraskeletal tissues. The skeletal functions of these hormones now extend beyond modulating bone resorption, and important extraskeletal activities have been discovered which involve unique local modes of action.