title: A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years.
abstract: Two trials have shown that a single 5-mg infusion of zoledronic acid achieves much higher response rates in Paget disease of bone than risedronate. The duration of this effect is unknown. We have conducted an open follow-up of responders from the two trials (152 originally treated with zoledronic acid, 115 with risedronate) out to 6.5 years without further intervention. Endpoints were times to relapse (ie, return of serum total alkaline phosphatase activity to within 20% of the pretreatment value) or loss of response (response = normalization of alkaline phosphatase or 75% or greater reduction in its excess). Bone turnover markers were lower in the zoledronic acid group throughout follow-up, with mean alkaline phosphatase (ALP) remaining within the reference range in these patients, whereas the mean in the risedronate group was above normal from 1 year. Relapse rates were substantially greater in the risedronate group (23 of 115, 20%) than in those treated with zoledronic acid (1 of 152, 0.7%, p < .001), and loss of response occurred in 19 (12.5%) zoledronic acid patients compared with 71 (62%) risedronate patients (p < .0001). Risk ratios for relapse and loss of response in zoledronic acid patients were 0.02 [95% confidence interval (CI) 0.00-0.18] and 0.12 (95% CI 0.07-0.19), respectively. Changes from baseline in quality of life, assessed using SF-36 scores, were more positive in the zoledronic acid group across the follow-up period (p = .01). Bone markers at 6 months were predictive of response duration. These data demonstrate an unprecedented duration of remission of Paget disease following treatment with zoledronic acid, accompanied by an improved quality of life.
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lyles
authors.forename: Guoqin
authors.initials: G
authors.lastname: Su
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.forename: Javier
authors.initials: J
authors.lastname: del Pino-Montes
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Susan
authors.initials: S
authors.lastname: Cafoncelli
authors.forename: Christina
authors.initials: C
authors.lastname: Bucci-Rechtweg
authors.forename: David J
authors.initials: DJ
authors.lastname: Hosking
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D010001:Osteitis Deformans / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D011877:Radionuclide Imaging; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase