Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta

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; Mahood 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

doi:10.1007/s00223-025-01440-3

Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta

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 HarveyE. Marelise W. Eekhoff, Johannes Feenstra, Geeta Hampson, Mike Stone, Jane Turton, Prashanth Patel, Mahood 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

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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.

Original language	English
Article number	136
Pages (from-to)	136
Number of pages	12
Journal	Calcified Tissue International and Musculoskeletal Research
Volume	116
Issue number	1
Early online date	8 Nov 2025
DOIs	https://doi.org/10.1007/s00223-025-01440-3
Publication status	Published - 8 Nov 2025

Bibliographical note

Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Keywords

Bisphosphonate; Clinical trial; Genetic; Osteogenesis imperfecta; Teriparatide.

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10.1007/s00223-025-01440-3Licence: CC BY 4.0

Baseline Characteristics of the TOPaZ Study - Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta
Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
Final published version, 845 KBLicence: CC BY 4.0

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Hald, J. D., Weir, C., Keerie, C., Dewar, L., MacLean, M., Milne, L., Keen, R., Walsh, J., Poole, K., Langdahl, B., Lindsay, J. R., Ghouri, N., Hollick, R. J., Aspray, T., Crowley, R. K., Cohen-Solal, M., Hassan Smith, Z., Tuck, S., Curtis, E., ... Ralston, S. H. (2025). Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta. Calcified Tissue International and Musculoskeletal Research, 116(1), 136. Article 136. https://doi.org/10.1007/s00223-025-01440-3

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title = "Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta",

abstract = "IntroductionOsteogenesis 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.MethodsWe summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.ResultsWe 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.ConclusionsThe 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.",

keywords = "Bisphosphonate; Clinical trial; Genetic; Osteogenesis imperfecta; Teriparatide.",

author = "Hald, {Jannie Dahl} and Christopher Weir and Catriona Keerie and Lorna Dewar and Morag MacLean and Lynsey Milne and Richard Keen and Jennifer Walsh and Kenneth Poole and Bente Langdahl and Lindsay, {John R.} and Nazim Ghouri and Hollick, {Rosemary J.} and Terry Aspray and Crowley, {Rachel K.} and Martine Cohen-Solal and {Hassan Smith}, Zaki and Stephen Tuck and Elizabeth Curtis and Nick Harvey and Eekhoff, {E. Marelise W.} and Johannes Feenstra and Geeta Hampson and Mike Stone and Jane Turton and Prashanth Patel and Mahood Siddiqi and Robin Munro and Matthew Roy and Zoe Paskins and Deepa Narayanan and Ellen Malcolm and Javaid, {Muhammad Kassim} and Patricia Osborne and Tang, {Jonathan C.Y.} and Wayne Lam and David Moore and Black, {Holly A.} and Duckworth, {Andrew D.} and Navnit Makaram and Tianyu Guo and Gregor Stenhouse and Ralston, {Stuart H.}",

note = "Copyright {\textcopyright} The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.",

year = "2025",

month = nov,

day = "8",

doi = "10.1007/s00223-025-01440-3",

language = "English",

volume = "116",

pages = "136",

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Hald, JD, Weir, C, Keerie, C, Dewar, L, MacLean, M, Milne, L, Keen, R, Walsh, J, Poole, K, Langdahl, B, Lindsay, JR, Ghouri, N, Hollick, RJ, Aspray, T, Crowley, RK, Cohen-Solal, M, Hassan Smith, Z, Tuck, S, Curtis, E, Harvey, N, Eekhoff, EMW, Feenstra, J, Hampson, G, Stone, M, Turton, J, Patel, P, Siddiqi, M, Munro, R, Roy, M, Paskins, Z, Narayanan, D, Malcolm, E, Javaid, MK, Osborne, P, Tang, JCY, Lam, W, Moore, D, Black, HA, Duckworth, AD, Makaram, N, Guo, T, Stenhouse, G & Ralston, SH 2025, 'Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta', Calcified Tissue International and Musculoskeletal Research, vol. 116, no. 1, 136, pp. 136. https://doi.org/10.1007/s00223-025-01440-3

Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta. / Hald, Jannie Dahl; Weir, Christopher; Keerie, Catriona et al.
In: Calcified Tissue International and Musculoskeletal Research, Vol. 116, No. 1, 136, 08.11.2025, p. 136.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Baseline Characteristics of the TOPaZ Study: 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, Mahood

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 - Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

PY - 2025/11/8

Y1 - 2025/11/8

N2 - IntroductionOsteogenesis 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.MethodsWe summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.ResultsWe 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.ConclusionsThe 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 - IntroductionOsteogenesis 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.MethodsWe summarised data on the baseline characteristics of TOPaZ participants, including demographics, genetic diagnosis, clinical features, bone density measurements, previous treatments, and fracture history.ResultsWe 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.ConclusionsThe 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; Clinical trial; Genetic; Osteogenesis imperfecta; Teriparatide.

UR - https://link.springer.com/article/10.1007/s00223-025-01440-3

UR - http://www.scopus.com/inward/record.url?scp=105021200686&partnerID=8YFLogxK

U2 - 10.1007/s00223-025-01440-3

DO - 10.1007/s00223-025-01440-3

M3 - Article

C2 - 41206390

SN - 1432-0827

VL - 116

SP - 136

JO - Calcified Tissue International and Musculoskeletal Research

JF - Calcified Tissue International and Musculoskeletal Research

IS - 1

M1 - 136

ER -

Baseline Characteristics of the TOPaZ Study: Randomised Trial of Teriparatide and Zoledronic Acid Compared with Standard Care in Adults with Osteogenesis Imperfecta

Abstract

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