High-dose pamidronate in the management of resistant Paget's disease

Current recommendations for the total dose of intravenous pamidronate to be used in the treatment of Paget's disease range up to 400 mg per course, although up to 980 mg has been suggested for resistant cases. However, in a proportion of Paget's disease patients remission is difficult to induce and maintain. In five patients with resistant symptomatic Paget's disease, in whom a variety of antipagetic therapies had failed to induce remission, we have examined the effects of high dose pamidronate (1.44-2.52 g intravenously over 12-42 weeks). All five subjects had a marked symptomatic improvement, and disease activity was suppressed to a greater extent than had been achieved previously, but in only one did alkaline phosphatase activity suppress into the normal range. A plateau in the biochemical response was evident, with successive pamidronate doses of 120 mg producing smaller decrements in alkaline phosphatase. The plateau was reproducible on repeated courses. Bone biopsies in two patients showed continued pagetic activity with an increased mineralization rate and no osteomalacia. Worthwhile clinical and biochemical improvements can be obtained in patients with resistant Paget's disease by the use of high-dose pamidronate. Though this approach does not seem to cause defective mineralization, it may be difficult to suppress disease activity completely.