Biochemical Analysis of the TOPAZ study
Research type
Research Study
Full title
Biochemical Analysis of the TOPAZ study
IRAS ID
360703
Contact name
Stuart H Ralston
Contact email
Sponsor organisation
University of Edinburgh
Clinicaltrials.gov Identifier
16/ES/0110 /207747, TOPAZ REC number / IRAS; 18/ES/0086 / 245197, ZIPP-LTE REC number /IRAS; 19/ES/0141 / 259285, GAPDPD REC number / IRAS
Duration of Study in the UK
0 years, 11 months, 30 days
Research summary
Osteogenesis imperfecta Osteogenesis imperfecta (OI) otherwise known as brittle bone disease is a rare genetic disorder characterised by increased bone fragility and multiple low trauma fractures (broken bones). A major impact of the disease is on the skeleton, OI is a systemic disorder which involves the cardiopulmonary and gastrointestinal system, soft tissues, tendons, muscle, joints, hearing, eyesight and dental health (Hald et al Calcified Tissue International 2024). While there is evidence that bone turnover is raised in OI the mechanisms are incompletely understood. A previous study showed that circulating concentrations of the biochemical marker sclerostin (SOST) were reduced in OI compared with people without OI (controls). (Nicol et al J Bone Miner Res. Feb 2018;33:307-15) In the same study SOST increased in response to teriparatide treatment which is a drug used to prevent fractures in people with osteoporosis (thinning of the bones). Other researchers have suggested that transforming growth factor beta (TGFß) is increased in OI and it has been proposed that this factor may increase bone remodelling and contribute to bone fragility in osteogenesis imperfecta (Song et al J Clin Invest. 2022;132). In this study here we propose to perform an analysis of circulating concentrations of SOST, the related cytokine Dkk1 and TGFß in stored serum samples from participants the TOPAZ clinical trial (4). We will relate the circulating concentration of these three factors to therapeutic response to treatment administered during the trial. The proposed study will clarify the role of SOST, Dkk1 and TGFß as biomarkers of disease severity and treatment response.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
25/YH/0179
Date of REC Opinion
22 Aug 2025
REC opinion
Favourable Opinion