Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta
Year: 2025
Type: article
Abstract: INTRODUCTION: Osteogenesis imperfecta (OI) is a rare disorder causing multiple fractures throughout life. No treatment has been shown to reduce the risk of fractures in OI. Here, we present the baseline characteristics of participants in the Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid (TOPaZ) trial. The aim of the trial is to determine whether teriparatide and zoledronic acid are superior to standard care in reducing the risk of clinical fractures. METHODS: We summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history. RESULTS: We recruited 350 adults with a clinical diagnosis of OI in 27 European referral centres between June 2017 and October 2022. Overall, 266 (76.2%) had type I OI, 55 (15.8%) had type IV, and 19 (5.4%) had type III. The type was unknown in 9 (2.6%). Blue sclera were noted in 80.8%, and 35.8% had dentinogenesis imperfecta. Bisphosphonates had been administered to 28.1% in the 2 years prior to enrolment. Pathogenic variants in COL1A1 or COL1A2 were found in 87.6%. Fractures occurring in the 2 years prior to enrolment were not associated with bone density. CONCLUSIONS: The TOPaZ population represents a unique cohort with which to study the genetic epidemiology and outcome of OI in relation to bone density and biochemical markers of bone turnover. When the trial reports, it will also provide new insights into the effect of an anabolic therapy, followed by antiresorptive treatment in the management of OI.
Source: Calcified Tissue International
Authors: Jannie Dahl Hald, Christopher Weir, Catriona Keerie, Lorna Dewar, Morag MacLean, Lynsey Milne, Richard Keen, Jennifer Walsh, Kenneth Poole, Bente Langdahl, John R. Lindsay, Nazim Ghouri, Rosemary J Hollick, Terry Aspray, Rachel K. Crowley, Martine Cohen-Solal, Zaki Hassan-Smith, Stephen Tuck, Elizabeth Curtis, Nick Harvey, E. Marelise W. Eekhoff, Johannes Feenstra, Geeta Hampson, Mike Stone, Jane Turton, Prashanth Patel, Mashood Siddiqi, Robin Munro, Matthew Roy, Zoe Paskins, Deepa Narayanan, Ellen Malcolm, Muhammad Kassim Javaid, Patricia Osborne, Jonathan C. Y. Tang, Wayne Lam, David Moore, Holly A. Black, Andrew D. Duckworth, Navnit Makaram, Tianyu Guo, Gregor Stenhouse, Stuart H. Ralston
Institutions: Aarhus University Hospital, University of Edinburgh, Royal National Orthopaedic Hospital NHS Trust, University of Sheffield, Addenbrooke's Hospital, Belfast Health and Social Care Trust, Musgrave Park Hospital, Royal Victoria Hospital, Queen Elizabeth University Hospital, University of Glasgow, University of Aberdeen, Freeman Hospital, Newcastle University, University College Dublin, St. Vincent's University Hospital, Inserm, Bioscar, Aston University, Queen Elizabeth Hospital Birmingham, South Tees Hospitals NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, MRC Lifecourse Epidemiology Unit, University of Southampton, Amsterdam Reproduction Development, Isala, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, University Hospital of Wales, University Hospital Llandough, University Hospitals of Leicester NHS Trust, Wishaw General Hospital, Bristol Royal Infirmary, Keele University, University of Hull, Ninewells Hospital, Nuffield Orthopaedic Centre, University of Oxford, Brittle Bone Society, National Health Service Scotland, NHS Lothian, Edinburgh Royal Infirmary, Western General Hospital, Institute of Genetics and Cancer
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,990
OpenAlex ID: W4416043235