Intravenously administered pamidronate in the treatment of Paget's disease of bone

To evaluate the effect of intravenously administered pamidronate in patients with Paget's disease of bone.

We conducted a prospective nonrandomized study and reviewed the related literature. Eighty patients (52 women and 28 men, ranging in age from 53 to 93 years; mean age, 76) were treated with pamidronate intravenously in a total dose of 180 mg during a 6- or 3-week period. All patients had bone scintigraphy and x-ray findings characteristic of Paget's disease of bone. Serum alkaline phosphatase levels were increased in all patients, and findings on fractionation were consistent with a bone origin. Indications for therapy included extensive disease, pagetic deformities, neurologic complications, pagetic pain, and critical areas of involvement. Blood chemistry profile and complete blood cell counts were determined at baseline and after the last dose of pamidronate. Serum calcium levels were determined after the first and second infusions of pamidronate. Patients underwent clinical and biochemical follow-up assessments, with serum alkaline phosphatase measurements, at 2- to 4-month intervals. Many patients who did not have a remission (defined as normalization of serum alkaline phosphatase level) after the first cycle of therapy or who had a relapse with serum alkaline phosphatase levels increased above the normal range after remission were treated with one or more cycles of intravenously administered pamidronate.

The mean serum alkaline phosphatase level was 1,051 U/L before therapy and 386 U/L after treatment, a decrease of 63% (P<0.0001). In 50 patients, the serum alkaline phosphatase level declined to normal. Such normalization was noted in 43 of 50 patients (86%) whose baseline alkaline phosphatase was less than 3 times the upper limit of normal (ULN), in 5 of 13 patients (38%) whose baseline alkaline phosphatase was 3 to 6 times the ULN, and in only 2 of 17 patients (12%) whose baseline alkaline phosphatase exceeded 6 times the ULN. Of 30 patients who did not have a remission, 22 received a second course of therapy, 2 of whom had normalization of the serum alkaline phosphatase level. Pamidronate was well tolerated; only nine patients reported a "flu-like" syndrome after the first infusion. Serum calcium levels decreased in many patients (to as low as 8 mg/dL), but no patients were symptomatic.

With intravenous administration of pamidronate in a dose of 180 mg in patients with Paget's disease of bone, remissions are likely in those whose baseline serum alkaline phosphatase level is <3 times the ULN and unlikely when baseline alkaline phosphatase levels are higher-especially more than 6 times the ULN.