Stuart Ralston Research Group

Section: Genetic and Experimental Medicine

Research in a Nutshell

The Ralston group's research focuses on the pathogenesis and treatment of patients with bone and joint disease.  In addition to conducting a wide range of research studies, the group has a strong focus on improving management of patients with bone disease. Professor Ralston is director of the Edinburgh Paget’s Disease Centre of Excellence (PACE) which was established by the Paget’s Association in 2015. The research group has also developed clinical tools for the management of patients with bone disease including the dietary calcium calculator and the osteoporosis risk benefit calculator (ORB) which allows clinicians and patients to estimate the risk of different fractures and how these might be impacted on by different treatments. The links to these tools are below:

  Calcium calculator           

  Osteoporosis risk-benefit calculator 

Research projects are being undertaken with the aim to gain greater understanding of the genetic determinants of bone and joint disease with the aim of tailoring treatments more effectively to improve clinical outcome for patients. There is a particular focus on rare bone diseases, including osteogenesis imperfecta, hereditary hypophosphataemic rickets, pregnancy associated osteoporosis and Paget’s disease of bone. Professor Ralston is chief investigator on the Zoledronate in the prevention of Paget’s disease trial (ZiPP) which is a ground-breaking study that seeks to determine if prophylactic treatment of patients genetically at high risk of developing Paget’s disease can alter the natural history of the disease and improve clinical outcome. More details are available at the ISRCTN website. http://www.isrctn.com/ISRCTN11616770

The ZiPP trial was scheduled to finish in 2020 but final study visits have been delayed due to the coronavirus pandemic. The final study visits were completed in December 2021, and it is expected that the results will be published during 2022.

Professor Ralston is also chief investigator on the Treatment of Osteogenesis Imperfecta with Teriparatide and Zoledronic acid trial (TOPaZ). This seeks to determine if a two-year course of Teriparatide followed by a single infusion of Zoledronic acid is superior to standard care in reducing the risk of fracture in osteogenesis imperfecta. More details are at the ISRCTN website: https://www.isrctn.com/ISRCTN15313991  This study has also been negatively impacted by the pandemic but is currently ongoing and has 261 recruits in follow up. New sites have just been initiated in Paris and Amsterdam.

Professor Ralston is chief investigator on the Pregnancy Associated Osteoporosis study (PAO) which is being supported by the Royal Osteoporosis Society. The study aims to find out more about the causes of Pregnancy Associated Osteoporosis, the natural history of the disease and its response to treatment. More details can be found at this link: PAO study.  

Preclinical and translational research is also being conducted into the genetic basis of Paget’s disease of bone funded by the European Commission as part of an advanced investigator award to Professor Ralston. New genes are being identified through extended genome wide association studies and candidate genes are being investigated using disease models.  A new study on genetic profiling called the Genetic Analysis to Prevent the Development of Paget’s Disease (GAPDPD) is due to start soon which will use genetic profiling to identify individuals at high risk of Paget’s disease. Dr Barbara Hauser a consultant rheumatologist and honorary senior lecturer within CGEM is the local principal investigator on the GAPDPD study.

Dr Nerea Alonso and Beatriz Larraz Prieto are investigating the genetic determinants of response to teriparatide to determine if genetic profiling could be of real clinical value in targeting treatment more effectively.  Functional analysis of the identified markers would help to develop new strategies to improve bone formation in non-responder patients.

Contact

Stuart.Ralston@ed.ac.uk

Collaborations

• Professor Bente Langdahl, University of Aarhus

Partners and Funders

• Arthritis Research UK
• Efficacy and Mechanisms Evaluation
• Paget’s Association