A single infusion of the bisphosphonate AHPrBP (APD) as treatment of Paget's disease of bone

Abstract

Purpose: Disabling pain, skeletal deformity, or risk of joint involvement characterize Paget's disease of bone. Because the disease often affects the elderly, for whom compliance is a problem, we investigated therapy with a single intravenous infusion of amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD).

Patients and methods: Eleven patients with mild but symptomatic Paget's disease and one patient with very severe disease were treated with AHPrBP administered as a single intravenous infusion of 60 mg over 24 hours. Follow-up with clinical and biochemical evaluations was performed over six months for all patients, and over one year for seven patients.

Results: Clinical improvement and normalization of biochemical parameters were observed in all patients except one with extremely severe disease. On average, plasma alkaline phosphatase activity fell progressively and significantly from 256 +/- 29 U/liter (mean +/- SEM) to 97 +/- 6 U/liter after six months, and to 102 +/- 11 U/liter after one year (normal: less than 120 U/liter). Urinary excretion of hydroxyproline decreased within seven days to normal (from 4.3 +/- 0.5 mumol/liter of glomerular filtrate [lGF] to 1.7 +/- 0.2 mumol/lGF; normal: 2.2 mumol/lGF). Thereafter, it remained within the normal range until one year (1.8 +/- 0.2 mumol/lGF after six months and 1.9 +/- 0.3 mumol/lGF after one year). Side effects were negligible. Two patients noted only a transient increase in body temperature. When bone scintigraphy was repeated after six months, it revealed a marked decrease of the activity of the disease.

Conclusion: Due to the important and sustained inhibition of bone resorption induced by AHPrBP, a single infusion of 60 mg of the bisphosphonate leads to a rapid decline in activity and a long-standing remission of moderate Paget's disease, without significant side effects.