Efficacy of the bisphosphonate APD in the control of Paget's bone disease

Abstract

Fifty-four patients with Paget's bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Paget's disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (≅ 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Paget's disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 ± 8.0 to 20.0 ± 3.9 KA units ( P ∠ 0.001) and urinary excretion of hydroxyproline diminished from 108.6 ± 16.9 to 42.4 ± 8.3 mg/24 h ( P ∠ 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment. It was found that the nonresponders had a shorter therapy-free interval as compared with the good responders. These observations indicate that APD is an effective agent in the long-term control of the activity of Paget's bone disease. No significant side effects have been observed in this group of patients.