Summary
Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorptionin 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×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<0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 μmol/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<0.02; Ga+: Acp 69.5±4.7 U/mg prot, Ga−: 57.5±2.8 U/mg prot,P<0.05). Serum iPTH was increased (Ga+: 112.9±17.6 pg/ml, Ga−: 41.4±7.4 pg/ml,P<0.01), serum calcium was reduced (Ga+: 2.4±0.02 mmol/l, Ga−: 2.6±0.03 mmol/l,P<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 μ/kg) was decreased 2 hours after injection of the hormone (ΔCa: TPTX Ga+: 0.11±0.04 mmol/l, Ga−: 0.33 ±0.03 mmol/lP<0.01). In conclusion, Ga, at the dosage used, does not inhibit the activity of osteoblasts in rats and does not interfere with mineralization but increases the number of osteoclasts through stimulation of parathyroid gland activity, induced by a fall in serum calcium. The hypocalcemia seems to be related to skeletal resistance to PTH and to increased renal calcium loss.
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Cournot-Witmer, G., Bourdeau, A., Lieberherr, M. et al. Bone modeling in gallium nitrate-treated rats. Calcif Tissue Int 40, 270–275 (1987). https://doi.org/10.1007/BF02555260
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DOI: https://doi.org/10.1007/BF02555260