ULTRASTRUCTURAL AND HISTOMORPHOMETRIC EVALUATIONS OF GALLIUM NITRATE ON BONE IN NUDE-MICE BEARING A CANINE ADENOCARCINOMA (CAC-8) MODEL OF HUMORAL HYPERCALCEMIA OF MALIGNANCY

Gallium is a group IIIa transition metal that lowers serum calcium by an unknown mechanism and has been utilized in the treatment of cancer- associated hypercalcemia. The purpose of this study was to histomorpho metrically investigate the ultrastructural effects of gallium nitrate on osteoclasts and osteoblasts in trabecular bone of normal nude mice and nude mice with humoral hypercalcemia of malignancy. Two groups of normal nude mice (n = 7 and n = 8, respectively) and two groups of hyp ercalcemic nude mice (n = 9) bearing a serially transplantable canine adenocarcinoma (CAC-8) were treated with vehicle or gallium nitrate. O steoclasts were hypertrophied in vehicle-treated tumor-bearing nude mi ce as compared with vehicle-treated nontumor-bearing nude mice. Osteoc lasts from tumor-bearing nude mice treated with gallium nitrate were s ignificantly decreased in size and had fewer intracytoplasmic vesicles as compared with osteoclasts from vehicle-treated tumor-bearing nude mice. Degenerate osteoclasts, characterized by pyknotic nuclei and inc reased cytoplasmic vacuolation, were observed in both groups of galliu m-treated nude mice. Osteoblasts from vehicle-treated tumor-bearing nu de mice were hypertrophied and had extensive lamellar arrays of rough endoplasmic reticulum as compared with osteoblasts from vehicle-treate d nontumor-bearing nude mice. Osteoblasts in gallium-treated nude mice (tumor-bearing and nontumor-bearing) were small and flattened with po orly developed cytoplasmic organelles. This investigation demonstrated that osteoclasts and osteoblasts in nude mice treated with gallium ni trate had ultrastructural evidence of decreased metabolic and function al activity. The results suggest that gallium nitrate lowers serum cal cium by inhibiting osteoclastic bone resorption.