Effect of gallium on thein vitro formation, growth, and solubility of hydroxyapatite

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Abstract
Gallium (Ga) is an effective treatment for the hypercalcemia of malignancy. The mechanism of action of the metal in blocking bone resorption in humans is not well understood. This paper examines the effect of Ga on thein vitro formation of hydroxyapatite (HA) in three test systems that have possible biological relevance in a pH-stat at pH 7.4, 37°C, and 0.15 M NaCl: (1) the direct precipitation of HA; (2) the transformation of amorphous calcium phosphate to HA; and (3) the growth of HA seeds. In addition, the effect of Ga on HA solubility was measured at pH 5.0, the approximate pH of osteoclastic bone resorption. Ga decreased the HA formation and/or growth kinetics in a dose-related manner in all three test systems. In addition, the time to the onset of HA formation was increased in systems 1 and 2. Also, the adsorption of Ga on the surface of HA crystals was measured. Ga reduced the dissolution kinetics of HA compared with Ga-free control. The mechanism reported herein—the significant adsorption of Ga on forming and growing HA nuclei and on the surface of HA crystals—is believed to be responsible for the effects of the metal on HA proliferation and solubility. Accumulation of the metal on newly formed metaphyseal bone can now be explained by this adsorption of Ga. Thesein vitro results partly explain thein vivo action of Ga in treating hypercalcemia by decreasing bone apatite solubility. The similarities in reducingin vitro HA formation rates of aluminum and Ga suggest that patients on long-term Ga therapy for any bone pathology should be carefully monitored for possible osteomalacic complication.