Journal of Clinical Endocrinology & Metabolism, Vol 80, 595-602, Copyright © 1995 by Endocrine Society
A multicenter trial of low dose gallium nitrate in patients with advanced Paget's disease of bone
RS Bockman, F Wilhelm, E Siris, F Singer, A Chausmer, R Bitton, J Kotler, BJ Bosco, DR Eyre and D Levenson
Department of Medicine, Hospital for Special Surgery, New York, New York 10021.
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.
