Short-term effects on bone and mineral metabolism of 4-amino-1-hydroxybutylidene-1,1-diphosphonate (ABDP) in Paget's disease of bone.

To study the short-term effects on mineral and bone metabolism of a recently introduced amino-diphosphonate (4-amino-1-hydroxybutylidene-1,1-diphosphonate or ABDP), 10 patients suffering from active Paget's disease were examined. Each subject received intravenously 5 mg/day of ABDP for 4 days and the effects of treatment were monitored for 12 days. ABDP administration was followed by an early and significant decrease of the urinary hydroxyproline and calcium excretion, of the theoretical renal threshold for phosphate of the serum calcium. Serum phosphate also decreased, while its urinary excretion increased. Intact parathyroid hormone levels at the end of treatment were four times higher than basal levels. Total and bone alkaline phosphatase tended to decrease only slightly at the end of the observation, whereas serum osteocalcin, tended to increase. These findings indicate that the earlier effect of ABDP is a profound inhibition of bone resorption, which brings about a compensatory parathyroid hormone response. The decrease of urinary hydroxyproline follows an exponential curve, with a calculated half-life of 2.2 days, suggesting an approximate equivalency of 5 mg/day ABDP to slightly more than 30 mg/day 3-amino-1-hydroxypropylidene-1,1-diphosphonate. Bone formation seems scarcely influenced in the short-term, but osteoblastic indices show a contrasting behaviour, which may reflect a different biological origin and/or significance.