We studied four treatment regimens of oral
alendronate in 60 patients with active Paget's disease. Two groups received an oral daily dose of either 40 or 80 mg of
alendronate for 3 months, followed by placebo for a further 3 months: the other two groups received treatment with 40 or 80 mg per day for 6 months. Activity of
alkaline phosphatase and urinary
hydroxyproline excretion were measured before, during, and
after treatment, at intervals for a total follow-up of 1 year. A transiliac bone biopsy was performed in 24 patients before and after the treatment. An additional 16 patients had a third biopsy more than a year after stopping treatment.
Alendronate induced a marked suppression in the urinary excretion of
hydroxyproline within 2 weeks (p < 0.01) followed by a fall in serum activity of
alkaline phosphatase at 1 month (p < 0.01) in all treatment groups. Nine months after the start of treatment patients treated with 80 mg for 6 months had a significantly lower mean
alkaline phosphatase activity compared to the other treatment groups (p < 0.02), which persisted at 1 year (p < 0.05).
Alkaline phosphatase decreased to within the laboratory reference range in all patients given 80 mg for 6 months. In contrast,
alkaline phosphatase decreased to within the laboratory reference range in 73-83% of patients given 80 mg for 3 months and the 40 mg dose. Histomorphometric assessment showed a decrease in indices of bone turnover in the pagetic biopsies. None of the biopsies taken
after treatment showed evidence of impaired mineralization of bone. Gastrointestinal side effects occurred in 25% of patients of whom two withdrew from treatment. We conclude that oral
alendronate is an effective agent for the treatment of
Paget's disease of bone.