[Cytokines in bone diseases. Cytokines and malignancy-associated hypercalcemia]

Malignancy-associated hypercalcemia is one of the commonest causes of hypercalcemia. Clinically, it has been subdivided into HHM (humoral hypercelcemia of malignancy) and LOH (local osteolytic hypercalcemia) . PTHrP (PTH related protein) , which has high homology with PTH in its N-terminus and binds to a common receptor (PTH1R) with PTH, plays a central role in the development of hypercalcemia in HHM. Although most features of HHM can be explained by excessive action of circulating PTHrP, decreased serum level of 1,25 (OH) (2)D and markedly suppressed bone formation found in HHM cannot be explained by the action of N-terminus of PTHrP. Fragments of PTHrP that do not bind to PTH1R, found in the circulation of HHM patients, or some other cytokines secreted by cancer cells may modify the clinical features of HHM. PTHrP also plays important roles in the development of LOH in some cancers, such as breast cancer. In this article, the role of cytokines, mainly PTHrP, in MAH will be reviewed.