Low dose intravenous 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) for the treatment of Paget's disease of bone

Twenty patients with severe symptomatic Paget's disease were treated with a series of 15 mg intravenous infusions of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD). A regimen of either five consecutive days of treatment (regimen 1) or a course of 12 weekly infusions was administered (regimen 2). In five cases regimen 2 followed regimen 1 after a three month interval. Alkaline phosphatase levels fell in all patients and returned to the normal range in 12. All but one of the patients obtained symptomatic improvement. There was a median fall in alkaline phosphatase activity of 63%. Eight patients observed a transient increase in bone pain starting about 24 hours after the first infusion. Intravenous APD was well tolerated, and we conclude that it is an effective treatment for Paget's disease; this route of administration avoids the problem of poor and unpredictable gastrointestinal absorption seen when a bisphosphonate is given orally. The optimal dose and duration of APD therapy, frequency of relapse, requirement for further courses, and merits relative to other second generation bisphosphonates remain to be established.