Non-weight bearing cohort study, version 1.0
Research type
Research Study
Full title
Evaluating the changes in muscle metabolic health and physical function in older people with non-weight bearing fractures: a longitudinal cohort study
IRAS ID
236583
Contact name
Eleanor Lunt
Contact email
Sponsor organisation
Nottingham Health Science Partners
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Summary of Research
The loss of muscle size and strength during immobility can be harmful to older people. Their ability to recover lost muscle function with rehabilitation after time spent inactive is greatly reduced compared to younger people. This causes poor walking ability, more chance of falls and more need for care at home or in a care home. The underlying processes causing older people to be so affected by immobility are unknown. Age-related muscle changes and altered muscle biochemistry may have a role.We will study men and women 70 years or older, who have an acute fracture, clinically managed with immobilisation and non-weight bearing. There are two parts to the study running together: a main cohort study (n=40) and a sub-study (n=20). Both parts will document the changes in muscle mass and strength at three time points during the first 6 weeks of immobilisation and at 4 months follow up. We aim to understand how changes in muscle function relate to clinical outcomes.
The sub-study will perform more detailed measurements of muscles using labelled drinks and examining urine tests, blood tests and small samples of muscle. Participants will be invited to participate in the sub-study if they are female and have an ankle fracture. There are no expected risks from taking part in the overall study, although there maybe side effects from muscle biopsies in the sub-study. This is an observational study so no intervention is being tested and the study will not interfere with clinical care. This study is being run from the NIHR Biomedical Research Centre at University of Nottingham and Nottingham University Hospitals NHS Trust. It is expected to start in April 2018 and to end in April 2020.
Summary of Results
As per the Declaration of End of Study Report, this study finished recruitment and follow up in June 2020, recruiting 50 rather than 60 participants as had been planned. The reason is that, although there were many potential participants, their frailty and co-pathology meant that many did not wish to give consent - despite considerable simplification of the protocol to reduce participant burden.This was a study done as a PhD study, alongside linked studies with volunteers under university research ethics committee governance. This explains why the analysis of the results and their interpretation is not yet complete. The PhD candidate in question is now on maternity leave, but prior to going on leave in October 2021 she had largely completed the analysis and is in the final stages of putting together her PhD thesis for final examination in 2022. At that point, she and the supervisory team will be ready swiftly to complete the papers on the work for publication.
The key findings of the research is that “clinically frail” people (the sorts of very old people who are seen in hospital with frailty syndromes such as lower limb fractures) show considerably more advanced age-related changes to the muscles than has conventionally been observed in volunteer studies, even in those meeting criteria for being frail. Their muscles are so wasted that conventional techniques to biopsy them, or to examine their structure by ultrasound are limited. We also observed that these muscles did not wither or weaken during hospitalisation as has been observed when fit young or older people are subject to experimental immobility. The implication is that the muscles of these people have been so under-used that they have largely “switched off”. The amount of metabolic activity of a muscle is related to its size and how it is used: these patients’ muscles were tiny and appeared to be barely used. The loss of function seen in hospital patients (hospital associated disability) in these cases cannot be explained by them wasting further, but due to non-muscular elements of deconditioning (e.g. psychological or pain) and environmental factors - and hence that targeting the muscles is unlikely to reduce hospital associated disability. Given that participants’ muscles were already startlingly wasted and weak at baseline, we assume that this is why they fell and fractured, and we surmise that these patients will have been chronically sedentary and inactive. Without addressing this underlying vulnerability state, we presume that these patients are destined to have further frailty events even after the fracture that brought them to our attention has healed. This poses an enormous challenge. We do not know if these people are beyond the point of no return and that their muscles cannot be switched back on. We can be certain that switching them back on will be very difficult and protracted since it would need to address all the factors that led to this state in the first place (ageing, disability, pain, motivation, and the social and physical environment). This leads us to the priorities for future research priorities, which include overcoming the principal challenges that prevent people from remaining active in their old age and predispose them to frailty: pain, cognitive impairment and lack of motivation.
REC name
Wales REC 6
REC reference
18/WA/0115
Date of REC Opinion
11 Apr 2018
REC opinion
Further Information Favourable Opinion