title: Duration of response with oral clodronate in Paget's disease of bone.
abstract: We studied retrospectively 51 patients with Paget's disease of bone treated with oral clodronate, 1600 mg daily given for 1 (n = 23), 3 (n = 13), or 6 months (n = 15), to compare the effect of a variable length of treatment on the response rate to treatment and the duration of disease suppression. Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before treatment at monthly intervals for a year and every 3 months thereafter until biochemical relapse. Before treatment, patients given the three regimens had similar disease activity as judged by serum alkaline phosphatase and urinary hydroxyproline values. There was no significant difference in the time to response between groups (median = 2 months). The proportion of patients attaining normal values of alkaline phosphatase activity was significantly higher in patients treated for 6 months (71%, p < 0.03) compared with those treated for 1 or 3 months (23% and 39%, respectively). The time to relapse from the start of treatment was significantly shorter in patients treated for 1 month compared with those treated for 3 or 6 months (median = 11, 18, and 23 months, respectively). Thus, at 2 years all patients treated for 1 month had relapsed, whereas 31% and 40% were still relapse-free in patients receiving treatment for 3 and 6 months, respectively. The length of treatment was the only variable identified by stepwise linear regression that significantly affected the duration of response. We conclude that oral clodronate (1600 mg daily) suppresses disease activity in the vast majority of patients with Paget's disease of bone. The magnitude of the response and its duration depend on the duration of treatment or the total dose administered, so that several months of treatment with oral clodronate are required when a durable response is desired.
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: E V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: K
authors.initials: K
authors.lastname: Nakatsuka
authors.forename: J
authors.initials: J
authors.lastname: Orgee
authors.forename: G M
authors.initials: GM
authors.lastname: Coombes
authors.forename: J A
authors.initials: JA
authors.lastname: Kanis
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000704:Analysis of Variance; D004002:Clodronic Acid / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000378:metabolism; D012044:Regression Analysis; D012074:Remission Induction / Q000379:methods; D019233:Retreatment; D012189:Retrospective Studies
chemical_list: D004002:Clodronic Acid; D000469:Alkaline Phosphatase; D006909:Hydroxyproline