Diphosphonate therapy of paget's disease of bone.
The use of disodium ethane-1 hydroxy-1, 1-diphosphonate (EHDP) therapy for Paget's disease of bone was examined in 75 affected patients. Forty-eight patients received randomly assigned oral doses of either 0, 2.5, 5, 10, or 20 mg/kg/day in a controlled, double-blind protocol, and the remainder received either 10 or 20 mg/kg/day in a non-random protocol. The clinical status of the patients and appropriate laboratory tests were evaluated before treatment and at frequent intervals during a six-month period of initial therapy. There were no significant changes in either urinary hydroxyproline or serum alkaline phosphatase in those patients receiving placebos, while both these parameters decreased significantly at all dose levels of EHDP, with the greatest decline noted in the highest dose group. However, statistical analysis of the data related to changes in symptoms in the double-blind study revealed that patients receiving the higher dose of EHDP (10 or 20 mg/kg/day) had less favorable outcomes than those receiving the lower doses (2.5 or 5 mg/kg/day). The high does group had a relatively lower rate of symptom improvement and a relatively greater rate of deterioration than did the low dose group. Twenty-one of forty-nine patients followed for at least 18 months have shown a sustained suppression of their serum alkaline phosphatase and urinary hydroxyproline values for 12 months following cessation of EHDP, while therapy has been reinstituted for the other 28 patients because of increases in these measurements, with or without accompanying symptomatic deterioration. Eight patients sustained fractures through Pagetic bone during the period of study and all of these were treated with higher doses of EHDP. On the basis of the biochemical and clinical data in this study it appears that initial therapy of Paget's disease of bone with 5 mg EHDP/kg/day maximizes benefits while minimizing possible adverse effects.