Effect of gallium on bone mineral properties

Summary

Gallium nitrate is biologically active in blocking bone rsorptionin vitro as well asin vivo. Administration of gallium nitrate to growing rats results in a dose-dependent accumulation of low levels of gallium in bone that is associated with specific changes in the mineral properties of bone. To elucidate in greater detail the changes induced by gallium, the properties of whole and density-fractionated bone samples from control and galliumtreated rats were examined. These studies showed that short-term treatment with gallium nitrate caused an increase in bone calcium and phosphate content. Devitalized bone powder from the gallium-treated rats was less soluble in acetate buffer and less readily resorbed by monocytes. Density fractionation analyses demonstrated that the largest proportion (76% by weight) of powdered metaphyseal bone particles from rats had a density of <2.15 g/cc. Following short-term treatment (14 days) with gallium nitrate (45 mg/kg body weight), a significant increase in the relative proportion of more dense bone (≥2.15 g/cc) was observed (24% for the control vs. 39% for the gallium-treated rats,P<0.01). In the diaphyseal samples, the largest proportion (88% by weight) of the bone powder had a density of ≥2.15 g/cc. After short-term treatment with gallium, a slight decrease in mean diaphyseal particle density was observed. Measurement of calcium accretion with⁴⁵Ca in the gallium-treated rats demonstrated increased specific activity in the metaphyseal bone samples, densities=2.0, 2.1, 2.15, and 2.25 g/cc; the difference was significant only for the 2.25 g/cc fraction. Therefore, short-term treatment with gallium nitrate leads to an increase in the calcium content of mature bone with more dense (more mineralized) bone particles accumulating in the metabolically more active metaphyseal bone. The data provide greater insight into the changes in bone properties induced afterin vivo treatment with gallium nitrate. However, the physiologic mechanisms by which these changes are effected are not known.