In vivo Morphologic Changes in the Rat Osteoclast Induced by Gallium Nitrate: The Result of Toxicity or Other Effects?

Abstract

Gallium nitrate, an approved antitumor drug, has found clinical application in the treatment of cancer-related hypercalcemia and of Paget’s disease; the exact mechanism of its action, however, remains unknown. The present study utilized rats in a 7-day exposure to gallium at doses similar to those used clinically. Quantitative histomorphometry and ultrastructural examination of osteoclast fine structure were carried out on specimens from animals with documented hypocalcemia. Gallium exposure produced striking changes in the osteoclast. The number of nuclei/osteoclast increased, and the ruffled borders of the osteoclasts were markedly decreased along the length of the Howship’s lacunar cavity. The absence of a decrease in osteoclast number and the types of changes seen in ultrastructure suggest that the mechanism of action of gallium seen here may differ from that of calcitonin, a nontoxic, reversible antiresorbing agent. Results underscore the difficulty in assessing the toxicity of agents such as gallium on the osteoclast, a mature differentiated cell which does not divide and which does not produce a characteristic extracellular matrix component.

Alterations in osteoclast morphology following long-term 17beta-estradiol administration in the mouse

“…The ultrastructural alterations identified in estrogen-treated mice were very likely the cellular functional basis for the decreased resorption and development of osteosclerosis in estrogen-treated mice. Osteoclast function and ultrastructural morphology have been shown to be highly responsive to anti-resorbing agents such as ethane-1-hydroxy-1,1-diphosphonate (EHDP) [8, 9], dichloromethylene diphosphanate (Cl 2 MDP) [10], calcitonin [11,12,13], other anti-resorptive agents, such as mithramycin [14], and to gallium nitrate [15]. …”