Gallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully
characterize the direct actions of GN on bone, we examined its effects on medium calcium,
medium β-glucuronidase (β-GLU), and collagen synthesis in control and hormone-stimulated
neonatal (4-6 days) mouse calvariae in vitro. GN (10 μg/ml) inhibited parathyroid
hormone-stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 μg/ml
of GN was required for complete inhibition; partial inhibition was seen with 12 h
preincubation; 1, 3, or 6 h was inadequate. A dose-response study showed that with
24 h preincubation, 5, 3, and 1 μg/ml of GN inhibited 81, 62, and 0% of PTH-induced
calcium release. The effects of GN on the release of β-GLU generally paralleled those
on the release of calcium except that 10 μg/ml of GN stimulated β-GLU release. Collagen
synthesis was inhibited 50% by 3 μg/ml of GN, whereas noncollagen protein synthesis
was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn
from the medium after 24 h of preincubation, the inhibitory effect on calcium release
and β-GLU activity, but not on collagen synthesis, persisted through the 72 h of culture.
GN also inhibited the resorption elicited by thyroxine (1 μM) and interleukin-1β (10
nM) but not by 1,25-dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a
powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses.
A preexposure time is required to induce the persistent effect, but the continuous
presence of GN is not necessary to maintain its effects on bone. Although GN has a
primary cellular site of action, the requirement for preculture could suggest that
GN could, in addition, make the bone matrix more resistant to resorption.