Paget's disease of bone treated in five days with AHPrBP (APD) per Os

Abstract

Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 ± 26 U/I (x̄ ± SEM) to 103 ± 10 U/I after 6 months (nl < 120 U/I). Urinary excretion of hydroxyproline decreased immediately and became normal (nl < 2.3 μmol/IGF) as a mean at day 5 (from 4.6 ± 0.4 μmol/IGF to 2.1 ± 0.3 μmol/IGF). Thereafter it remained within the normal range (2.0 ± 0.2 μmol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.