Article Text
PDF
Abstract
Introduction Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI.
Methods and analysis Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL.
Ethics and dissemination The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care.
Trial registration number ISRCTN15313991.
- randomized controlled trial
- internal medicine
- rheumatology
- calcium & bone
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Footnotes
Twitter @Stu_Ralston
Contributors First draft of the manuscript: JDH and SR; Study concept and design: SR; Obtaining funding SR, CW, KJ, WL, PO, JW and BLL. All authors commented on and revised the manuscript for intellectual content and approved the final version of the manuscript.
Funding The study was funded by the Efficacy and Mechanism Evaluation (EME) Programme (reference EME 14/200/18) which is a partnership between the UK Medical Research Council (MRC) and the National Institute of Health Research. The teriparatide was kindly donated by Eli Lilly Pharmaceuticals. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any author accepted manuscript version arising from this submission.
Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. The funder and Eli Lilly had no role in study design, data collection, management, analysis, interpretation, writing of the report nor the decision to submit the report for publication.
Competing interests All authors report funding from the Efficacy and Mechanism Evaluation programme of the NIHR and non-financial support from Eli Lilly to support this work. BLL reports research grants from Mereo Pharmaceuticals outside this work and consultancy funding from Amgen, UCB, and Gedeon Richter. PO reports that she is an employee of the Brittle Bone Society. SR reports research grants from Kyowa Kirin and Astra-Zeneca outside the submitted work and funding to his institution from Pfizer, Abbvie, Kyowa Kirin, Alexion, Amgen, Cellgene, Janssen-Cilag, Novartis, Eli Lilly, Thornton & Ross, and Sanofi Genzyme and UCB outside the submitted work. SR also reports that he is a member of the Scientific Advisory Board of the Brittle Bone Society. KJ reports consultancy funding from Amgen outside the submitted work and reports that he is chair of the Medical Advisory Board of the Brittle Bone Society. JW reports that she is a member of the Medical Advisory Board of the Brittle Bone Society. CK and CW have no other conflicts of interest to declare.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; peer reviewed for ethical and funding approval prior to submission.