Gallium nitrate

A high incidence of hypercalcemia is often observed in patients with non-small cell lung cancer, breast cancer, multiple myeloma, kidney cancer, and cancer of head and neck. Hypercalcemia of malignancy seems to result from an imbalance between the net resorption of bone and urinary excretion of calcium. Patients with extensive osteolytic bone metastases frequently develop hypercalcemia. Although in vitro and animal studies have been performed to investigate the mechanism of action of gallium nitrate, the precise mechanism for inhibiting calcium resorption has not been determined. Gallium, the active component that exerts the physiological effects of gallium nitrate, may induce physicochemical changes in the bone matrix to promote hydroxyapatite crystallization and attenuate mineral dissolution. Gallium may also decrease acid secretion by osteoclasts and modulate the synthesis of osteocalcin, an osteoblast-specific bone matrix protein that triggers bone resorption. Osteoclast morphology or viability is not reported to be affected.

Gallium nitrate may modulate inflammation. In vitro, it was shown to block the production of inflammatory cytokines, such as interleukin-1 (IL-1) beta, by macrophage-like cells. Gallium nitrate also dose-dependently inhibited matrix metalloproteinase activity promoted by tissue plasminogen activator (tPA).