Gallium nitrate is a potent antiresorptive
drug that has been extensively tested in patients with accelerated bone turnover. We have evaluated the effects of this new agent in a pilot multicenter trial of 49 patients with advanced
Paget's disease of bone. Patients were randomized to receive 0.05, 0.25, or 0.5 mg/kg.day
gallium nitrate administered by sc injection in two 14-day cycles. Serum
alkaline phosphatase, fasting 2-h urinary
hydroxyproline and
N- telopeptide collagen cross-links excretion, and quality of life were assessed every 2 weeks for 12 weeks. The group mean
alkaline phosphatase activity at baseline was 854 +/- 100 (+/- SEM) IU/L. The mean changes from baseline to week 12 in serum
alkaline phosphatase were +0.5%, -24%, and -31%, respectively, for the three doses tested. The differences for each of the higher dose levels (0.25 and 0.5 mg/kg.day) was statistically significant (P < or = 0.05), and nearly half of the patients treated with the 0.5 mg/kg.day dose achieved a 50% or more reduction in
enzyme activity. The nadir value in
hydroxyproline excretion occurred
at 10 weeks, with mean changes of +9%, -10%, and -17% for the 0.05, 0.25, and 0.5 mg/kg.day doses, respectively; the difference was significant only at the 0.5 mg/kg.day level (P < 0.01). Urinary
collagen cross-link excretion showed a significant decrease at the 0.25 and 0.5 mg/kg.day doses. We also observed a definite, but nonsignificant, trend for improved quality of life in patients treated at the highest
drug dose. Minor discomfort at the injection site was frequently reported, but did not lead to interruption of
therapy. Our results in these patients who had received moderate to extensive prior
therapies with other drugs show that cyclical, low dose, sc administration of
gallium nitrate is safe and effective for treating patients with advanced
Paget's disease of bone.