Objective. To determine whether resistance to one bisphosphonate predicts resistance to another bisphosphonate. Methods. One hundred patients with Paget's disease were treated with intravenous (IV) pamidronate. The initial dose was 120 mg; followed by further doses of 240 mg, until either biochemical remission was achieved or a total dose of 1 gm was given. Biochemical remission was defined as an alkaline phosphatase level within the reference range. Patients whose disease failed to respond to pamidronate were then treated with alendronate for 6 months: Patients whose disease failed to respond to alendronate Were given either tiludronate for 3 months, or clodronate for 6 months. Results. Sixteen of the 100. patients treated with pamidronate failed to achieve a biochemical response despite a cumulative dose of 1 gm. Of the 16 nonresponders, 1 died of an unrelated cause, and the remaining 15 patients were treated with alendronate. In 2 of these patients, the treatment was changed to another bisphosphonate because of gastrointestinal intolerance to alendronate. Of the remaining 13 patients, 9 (69%) achieved full biochemical remission. In 4 other patients, both pamidronate and alendronate therapy were unsuccessful (1 patient responded to tiludronate, tiludronate therapy was unsuccessful in 1, clodronate was unsuccessful in 1, and 1 patient elected to receive no further treatment). Of the 2 patients who could not receive alendronate because of gastrointestinal intolerance, 1 achieved normalization with tiludronate, and a repeat course of pamidronate was unsuccessful in the other. In total, 73% of patients in whom initial treatment with IV pamidranate was unsuccessful responded to a change in bisphosphonate treatment. Conclusion. Failure to achieve biochemical normalization is likely to be specific to the-individual drug rather than indicative of bisphosphonate class, resistance.
