title: Long-Term Effects of Intravenous Ibandronate in Paget's Disease of Bone.
abstract: We have previously demonstrated that intravenous ibandronate produces high initial response rates in Paget's disease, but the durability of this effect is unknown. It might be expected to be short lived because ibandronate has a low affinity for bone. Here we report long-term follow-up (up to 14 years) of patients from that trial. Twenty-five patients with active Paget's disease [baseline serum total alkaline phosphatase (ALP) ~3 times the upper limit of normal] received either 6 or 12 mg intravenous ibandronate at baseline. There were prompt reductions in ALP following treatment, with normalization in 88%. ALP remained in the normal range in most patients for 20-30 months, but some subjects then showed gradual increases. Three years after ibandronate, before any patients had received additional treatment, ALP was normal in 61%. Six patients maintained normal ALP beyond 6 years without further intervention. Responses to 6 and 12 mg were similar. These results indicate that long-term remissions in Paget's disease can be achieved with bolus delivery of a potent bisphosphonate, even if the drug has a low affinity for bone. Therefore, bisphosphonate retention in bone might not be the only factor determining duration of remission. Intravenous bisphosphonates are likely to produce high drug concentrations within pagetic lesions which might result in cytotoxicity to the pagetic cells, leading to long durations of remission. These findings strengthen the evidence that potent bisphosphonates delivered in a single intravenous dose are a very efficient way to manage this condition.
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. i.reid@auckland.ac.nz.|Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand. i.reid@auckland.ac.nz.
authors.forename: Ian R
authors.identifier: 0000-0001-6021-5458
authors.initials: IR
authors.lastname: Reid
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Diana
authors.initials: D
authors.lastname: Wattie
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Rheumatology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Ramanamma
authors.initials: R
authors.lastname: Kalluru
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Tim
authors.initials: T
authors.lastname: Cundy
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077557:Ibandronic Acid; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000188:drug therapy*; D013995:Time; D013997:Time Factors
chemical_list: D004164:Diphosphonates; D002118:Calcium; D000077557:Ibandronic Acid
keywords: Bisphosphonates; Ibandronate; Paget’s disease; Zoledronate; Zoledronic acid