Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.

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dc.contributor.author Cronin, Owen
dc.contributor.author Forsyth, Laura
dc.contributor.author Goodman, Kirsteen
dc.contributor.author Lewis, Steff C
dc.contributor.author Keerie, Catriona
dc.contributor.author Walker, Allan
dc.contributor.author Porteous, Mary
dc.contributor.author Cetnarskyj, Roseanne
dc.contributor.author Ranganath, Lakshminarayan R
dc.contributor.author Selby, Peter L
dc.contributor.author Hampson, Geeta
dc.contributor.author Chandra, Rama
dc.contributor.author Ho, Shu
dc.contributor.author Tobias, Jon H
dc.contributor.author Young-Min, Steven
dc.contributor.author McKenna, Malachi J
dc.contributor.author Crowley, Rachel K
dc.contributor.author Fraser, William D
dc.contributor.author Gennari, Luigi
dc.contributor.author Nuti, Ranuccio
dc.contributor.author Brandi, Maria Luisa
dc.contributor.author Del Pino-Montes, Javier
dc.contributor.author Devogelaer, Jean-Pierre
dc.contributor.author Durnez, Anne
dc.contributor.author Isaia, Giancarlo
dc.contributor.author Di Stefano, Marco
dc.contributor.author Guañabens, Núria
dc.contributor.author Blanch, Josep
dc.contributor.author Seibel, Markus J
dc.contributor.author Walsh, John P
dc.contributor.author Kotowicz, Mark A
dc.contributor.author Nicholson, Geoffrey C
dc.contributor.author Duncan, Emma L
dc.contributor.author Major, Gabor
dc.contributor.author Horne, Anne
dc.contributor.author Gilchrist, Nigel L
dc.contributor.author Boers, Maarten
dc.contributor.author Murray, Gordon D
dc.contributor.author Charnock, Keith
dc.contributor.author Wilkinson, Diana
dc.contributor.author Russell, R Graham G
dc.contributor.author Ralston, Stuart H
dc.coverage.spatial England
dc.date.accessioned 2020-12-09T03:21:07Z
dc.date.available 2020-12-09T03:21:07Z
dc.date.issued 2019-9-4
dc.identifier.citation BMJ open 9(9):e030689 04 Sep 2019
dc.identifier.issn 2044-6055
dc.identifier.uri http://hdl.handle.net/2292/54024
dc.description.abstract INTRODUCTION:Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS:People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION:The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER:ISRCTN11616770.
dc.format.medium Electronic
dc.language eng
dc.publisher BMJ
dc.relation.ispartofseries BMJ open
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Paget’s Disease of Bone
dc.subject SQSTM1, genetics
dc.subject Zoledronic acid
dc.subject bisphosphonate
dc.subject randomized controlled trial
dc.subject Adult
dc.subject Anxiety
dc.subject Bone Density Conservation Agents
dc.subject Depression
dc.subject Genetic Testing
dc.subject Humans
dc.subject Musculoskeletal Pain
dc.subject Mutation
dc.subject Osteitis Deformans
dc.subject Quality of Life
dc.subject Radionuclide Imaging
dc.subject Randomized Controlled Trials as Topic
dc.subject Sequestosome-1 Protein
dc.subject Zoledronic Acid
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Medicine, General & Internal
dc.subject General & Internal Medicine
dc.subject Paget's Disease of Bone
dc.subject bisphosphonate
dc.subject Zoledronic acid
dc.subject SQSTM1
dc.subject genetics
dc.subject randomized controlled trial
dc.subject BRIEF PAIN
dc.subject MUTATIONS
dc.subject SEQUESTOSOME-1
dc.subject INVENTORY
dc.subject SEVERITY
dc.subject 1103 Clinical Sciences
dc.subject Clinical
dc.subject Clinical Medicine and Science
dc.subject Prevention
dc.subject Clinical Trials and Supportive Activities
dc.subject Aging
dc.subject Clinical Research
dc.subject Musculoskeletal
dc.subject 1103 Clinical Sciences
dc.subject 1117 Public Health and Health Services
dc.subject 1199 Other Medical and Health Sciences
dc.title Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.
dc.type Journal Article
dc.identifier.doi 10.1136/bmjopen-2019-030689
pubs.issue 9
pubs.begin-page e030689
pubs.volume 9
dc.date.updated 2020-11-26T19:54:43Z
dc.rights.holder Copyright: The author en
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/31488492
pubs.publication-status Published
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype protocol
pubs.subtype Journal Article
pubs.elements-id 782799
dc.identifier.eissn 2044-6055
dc.identifier.pii bmjopen-2019-030689
pubs.number ARTN e030689
pubs.online-publication-date 2019-9-4

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