Gallium nitrate for advanced Paget disease of bone: effectiveness and dose-response analysis.

OBJECTIVE

To evaluate whether a brief course of treatment with gallium nitrate can reduce biochemical parameters of accelerated bone turnover in patients with advanced Paget disease.

DESIGN

Unblinded trial, decreasing dose schedules of gallium nitrate.

SETTING

University hospital with primary orthopedic and metabolic bone disease specialty.

PATIENTS

Ten patients with advanced Paget disease who had previously received conventional therapy consisting of calcitonin, etidronate, or mithramycin.

INTERVENTIONS

Five patients were entered into each of three dose schedules: 2.5 mg/kg body weight per day by continuous intravenous infusion for 7 days; 0.5 mg/kg per day for 14 days by subcutaneous injection; and 0.25 mg/kg per day for 14 days by subcutaneous injection. Several patients were treated with different dose schedules. Patients were followed until relapse.

RESULTS

Fifteen courses of treatment were administered to ten patients. Reductions in serum alkaline phosphatase and urinary hydroxyproline excretion were observed after treatment with each dose schedule. After treatment with high, intermediate, and low doses, the median maximum decreases in serum alkaline phosphatase activity were 49%, 39%, and 18%, respectively. The median maximum decreases in urinary hydroxyproline excretion were 50%, 52%, and 16%, respectively. The maximum decrease in urinary hydroxyproline excretion occurred within a median of 2 weeks from the start of treatment, whereas the maximum decrease in serum alkaline phosphatase activity occurred substantially later at a median of 6 weeks. All treatment schedules were well tolerated. Response duration was highly variable (range, 6 to 42 weeks).

CONCLUSIONS

Short-term treatment with gallium nitrate can reduce biochemical parameters of disease activity in patients with advanced Paget disease of bone. Larger trials using low-dose intermittent treatment schedules are required to evaluate the safety and effectiveness of this therapy.