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
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 th...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2019 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/182615 |
| Online Access: | https://hdl.handle.net/2445/182615 |
| Access Level: | Open access |
| Keyword: | Genètica Malalties dels ossos Genetics Bone diseases |
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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 boneCronin, OwenForsyth, LauraGoodman, KirsteenLewis, Steff C.Keerie, CatrionaWalker, AllanPorteous, MaryCetnarskyj, RoseanneRanganath, Lakshminarayan R.Selby, Peter L.Hampson, GeetaChandra, RamaHo, ShuTobias, Jon H.Young-Min, StevenMcKenna, Malachi J.Crowley, Rachel K.Fraser, William D.Gennari, LuigiNuti, R.Brandi, Maria LuisaDel Pino-Montes, JavierDevogelaer, Jean PierreDurnez, AnneIsaia, GiancarloDi Stefano, MarcoGuañabens Gay, NúriaBlanch, JosepSeibel, Markus J.Walsh, John P.Kotowicz, Mark A.Nicholson, Geoffrey C.Duncan Emma L.Major, GaborHorne, AnneGilchrist, Nigel L.Boers, MaartenMurray, Gordon D.Charnock, KeithWilkinson, DianaGenèticaMalalties dels ossosGeneticsBone diseasesIntroduction: 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.BMJ Publishing Group2022202220192022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/182615Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1136/bmjopen-2019-030689BMJ Open, 2019, vol. 9, num. 9https://doi.org/10.1136/bmjopen-2019-030689cc-by (c) Cronin, Owen et al., 2019https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1826152026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
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 |
| 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 |
| spellingShingle |
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 Cronin, Owen Genètica Malalties dels ossos Genetics Bone diseases |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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.creator.none.fl_str_mv |
Cronin, Owen Forsyth, Laura Goodman, Kirsteen Lewis, Steff C. Keerie, Catriona Walker, Allan Porteous, Mary Cetnarskyj, Roseanne Ranganath, Lakshminarayan R. Selby, Peter L. Hampson, Geeta Chandra, Rama Ho, Shu Tobias, Jon H. Young-Min, Steven McKenna, Malachi J. Crowley, Rachel K. Fraser, William D. Gennari, Luigi Nuti, R. Brandi, Maria Luisa Del Pino-Montes, Javier Devogelaer, Jean Pierre Durnez, Anne Isaia, Giancarlo Di Stefano, Marco Guañabens Gay, Núria Blanch, Josep Seibel, Markus J. Walsh, John P. Kotowicz, Mark A. Nicholson, Geoffrey C. Duncan Emma L. Major, Gabor Horne, Anne Gilchrist, Nigel L. Boers, Maarten Murray, Gordon D. Charnock, Keith Wilkinson, Diana |
| author |
Cronin, Owen |
| author_facet |
Cronin, Owen Forsyth, Laura Goodman, Kirsteen Lewis, Steff C. Keerie, Catriona Walker, Allan Porteous, Mary Cetnarskyj, Roseanne Ranganath, Lakshminarayan R. Selby, Peter L. Hampson, Geeta Chandra, Rama Ho, Shu Tobias, Jon H. Young-Min, Steven McKenna, Malachi J. Crowley, Rachel K. Fraser, William D. Gennari, Luigi Nuti, R. Brandi, Maria Luisa Del Pino-Montes, Javier Devogelaer, Jean Pierre Durnez, Anne Isaia, Giancarlo Di Stefano, Marco Guañabens Gay, Núria Blanch, Josep Seibel, Markus J. Walsh, John P. Kotowicz, Mark A. Nicholson, Geoffrey C. Duncan Emma L. Major, Gabor Horne, Anne Gilchrist, Nigel L. Boers, Maarten Murray, Gordon D. Charnock, Keith Wilkinson, Diana |
| author_role |
author |
| author2 |
Forsyth, Laura Goodman, Kirsteen Lewis, Steff C. Keerie, Catriona Walker, Allan Porteous, Mary Cetnarskyj, Roseanne Ranganath, Lakshminarayan R. Selby, Peter L. Hampson, Geeta Chandra, Rama Ho, Shu Tobias, Jon H. Young-Min, Steven McKenna, Malachi J. Crowley, Rachel K. Fraser, William D. Gennari, Luigi Nuti, R. Brandi, Maria Luisa Del Pino-Montes, Javier Devogelaer, Jean Pierre Durnez, Anne Isaia, Giancarlo Di Stefano, Marco Guañabens Gay, Núria Blanch, Josep Seibel, Markus J. Walsh, John P. Kotowicz, Mark A. Nicholson, Geoffrey C. Duncan Emma L. Major, Gabor Horne, Anne Gilchrist, Nigel L. Boers, Maarten Murray, Gordon D. Charnock, Keith Wilkinson, Diana |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Genètica Malalties dels ossos Genetics Bone diseases |
| topic |
Genètica Malalties dels ossos Genetics Bone diseases |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2022 2022 2022 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/182615 |
| url |
https://hdl.handle.net/2445/182615 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1136/bmjopen-2019-030689 BMJ Open, 2019, vol. 9, num. 9 https://doi.org/10.1136/bmjopen-2019-030689 |
| dc.rights.none.fl_str_mv |
cc-by (c) Cronin, Owen et al., 2019 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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cc-by (c) Cronin, Owen et al., 2019 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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9 p. application/pdf |
| dc.publisher.none.fl_str_mv |
BMJ Publishing Group |
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BMJ Publishing Group |
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Articles publicats en revistes (Medicina) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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