HIGH-DOSE PAMIDRONATE IN THE MANAGEMENT OF RESISTANT PAGETS-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 diff icult to induce and maintain. In five patients with resistant symptoma tic Paget's disease, in whom a variety of antipagetic therapies had fa iled to induce remission, we have examined the effects of high dose pa midronate (1.44-2.52 g intravenously over 12-42 weeks). All five subje cts had a marked symptomatic improvement, and disease activity was sup pressed to a greater extent than had been achieved previously, but in only one did alkaline phosphatase activity suppress into the normal ra nge. A plateau in the biochemical response was evident, with successiv e pamidronate doses of 120 mg producing smaller decrements in alkaline phosphatase. The plateau was reproducible on repeated courses. Bone b iopsies in two patients showed continued pagetic activity with an incr eased mineralization rate and no osteomalacia. Worthwhile clinical and biochemical improvements can be obtained in patients with resistant P aget's disease by the use of high-dose pamidronate. Though this approa ch does not seem to cause defective mineralization, it may be difficul t to suppress disease activity completely.