TY - JOUR
T1 - Baseline Characteristics of the TOPaZ Study
T2 - Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta
AU - Hald, Jannie Dahl
AU - Weir, Christopher
AU - Keerie, Catriona
AU - Dewar, Lorna
AU - MacLean, Morag
AU - Milne, Lynsey
AU - Keen, Richard
AU - Walsh, Jennifer
AU - Poole, Kenneth
AU - Langdahl, Bente
AU - Lindsay, John R.
AU - Ghouri, Nazim
AU - Hollick, Rosemary J.
AU - Aspray, Terry
AU - Crowley, Rachel K.
AU - Cohen-Solal, Martine
AU - Hassan-Smith, Zaki
AU - Tuck, Stephen
AU - Curtis, Elizabeth
AU - Harvey, Nick
AU - Eekhoff, E. Marelise W.
AU - Feenstra, Johannes
AU - Hampson, Geeta
AU - Stone, Mike
AU - Turton, Jane
AU - Patel, Prashanth
AU - Siddiqi, Mashood
AU - Munro, Robin
AU - Roy, Matthew
AU - Paskins, Zoe
AU - Narayanan, Deepa
AU - Malcolm, Ellen
AU - Javaid, Muhammad Kassim
AU - Osborne, Patricia
AU - Tang, Jonathan C. Y.
AU - Lam, Wayne
AU - Moore, David
AU - Black, Holly A.
AU - Duckworth, Andrew D.
AU - Makaram, Navnit
AU - Guo, Tianyu
AU - Stenhouse, Gregor
AU - Ralston, Stuart H.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12/1
Y1 - 2025/12/1
N2 - 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.
AB - 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.
KW - Bisphosphonate
KW - Clinical trial
KW - Genetic
KW - Osteogenesis imperfecta
KW - Teriparatide
UR - https://www.scopus.com/pages/publications/105021200686
U2 - 10.1007/s00223-025-01440-3
DO - 10.1007/s00223-025-01440-3
M3 - Article
C2 - 41206390
SN - 0171-967X
VL - 116
JO - Calcified tissue international
JF - Calcified tissue international
IS - 1
M1 - 136
ER -