Bone modeling in gallium nitrate-treated rats.

ABSTRACT

Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorption in vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.75 mg elemental gallium i.p. QOD X 8, Ga+), and controls received the solvent (Ga-). In the bone of Ga+ rats the number of osteoclasts was increased (Ga+ 70.4 +/- 2.31 osteoclasts/mm2; Ga- 46.5 +/- 1.61 osteoclasts/mm2, P less than 0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 mumol/g cortical bone) and detected by electron microprobe on the surface of a few trabeculae. Alkaline (Alp) and acid (Acp) phosphatase activities were higher in Ga+ than in Ga- calvaria (Ga+ Alp 223 +/- 23.4 U/mg prot, Ga- Alp 145 +/- 13.3 U/mg prot, P less than 0.02; Ga+ Acp 69.5 +/- 4.7 U/mg prot, Ga- 57.5 +/- 2.8 U/mg prot, P less than 0.05). Serum iPTH was increased (Ga+ 112.9 +/- 17.6 pg/ml, Ga- 41.4 +/- 7.4 pg/ml, P less than 0.01), serum calcium was reduced (Ga+ 2.4 +/- 0.02 mmol/l, Ga- 2.6 +/- 0.03 mmol/l, P less than 0.001); calciuria remained comparable to controls. Relative to the hypocalcemia this suggests renal loss of Ca. The calcemic response to hPTH 1-34 (i.v. 50 micrograms/kg) was decreased 2 hours after injection of the hormone (delta Ca TPTX Ga+ 0.11 +/- 0.04 mmol/l, Ga- 0.33 +/- 0.03 mmol/l P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)