title: Alendronate in the treatment of Paget's disease of bone.
abstract: 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.
authors.affiliation: WHO Collaborating Centre for Metabolic Bone Disease, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
authors.forename: S
authors.initials: S
authors.lastname: Vasikaran
authors.forename: E V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: M N
authors.initials: MN
authors.lastname: Benéton
authors.forename: S
authors.initials: S
authors.lastname: Rogers
authors.forename: L
authors.initials: L
authors.lastname: Coulton
authors.forename: J
authors.initials: J
authors.lastname: Orgee
authors.forename: G
authors.initials: G
authors.lastname: Coombes
authors.forename: J A
authors.initials: JA
authors.lastname: Kanis
mesh_terms: D000368:Aged; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D002118:Calcium / Q000097:blood*; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine*; D008297:Male; D010001:Osteitis Deformans / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate