BioGrOA: Imaging joint biomechanics in growth and osteoarthritis

Throughout life, our joints change continuously and adapt to the varying and often huge loads placed upon them as we walk, run, lift and jump. However, as we get older our joints undergo structural changes that may lead to the aching and stiffness that is often associated with ageing.

Osteoarthritis is the most important ageing-related disease affecting almost 9 million people in the UK. It is estimated that more than 33% of the UK population aged over 45 have sought treatment for osteoarthritis. For this reason, osteoarthritis is a major financial, social and healthcare burden. Osteoarthritic joints, most often knees and hips, undergo structural deterioration, characterised by loss of the joint cartilage which covers the bone and normally allows pain-free joint movement.

Current osteoarthritis treatments are limited and largely consist of the use of pain-killers and physiotherapy. In some individuals, osteoarthritis progresses to the extent that total joint replacement is required. Currently we are unable to identify those at risk of developing osteoarthritis. We are also unable to treat those at early disease stages. This proposal will change this by identifying whether the way in which the skeleton grows during childhood and adolescence, changes how joint structures adapt to the huge loads placed upon them.

Our research team has developed new imaging technologies to enable us to address this. Using this technology, we are now able to image mouse knee joints whilst they are experiencing loading, like that is seen in our everyday life. We are able to see how the cartilage and the bones of the joint react to these loads, and most importantly, how they change their structure in response to this. Therefore, we will apply this technology to mouse knee joints which we know grow very quickly in early life, and which develop osteoarthritis with ageing. We will also examine a large cohort of human patients to see if their joints have changed their shape in response to their childhood and adolescence growth.

This research will identify if there are specific joint structures which change with loading and ageing, and therefore will offer clues into who may develop osteoarthritis. Further, it will identify if height during childhood and adolescence can predispose someone to joint changes linked to osteoarthritis. Together, this will allow us to better identify those at risk of osteoarthritis and therefore will have huge patient benefit. This is vital if we are to reduce the healthcare and economic burden of this disease.

Osteoarthritis (OA), characterised by articular cartilage loss, affects almost 9 million people in the UK and is a major financial, social and healthcare burden. Advancing our understanding of the mechanisms underpinning disease aetiology will enable us to deliver new paradigms to identify those at risk of OA, and to deliver personalised interventions to treat patients with OA.

Our previous research has identified associations between growth plate cartilage phenotypes and OA development. Further, we have developed new synchrotron X-ray imaging technologies to allow determination of nanoscale mechanical strains in intact joints under loading. Here we will build on this work and for the first time will use a unique integration of approaches and resources in musculoskeletal biology, epidemiology, biomechanics and imaging to examine our hypothesis that: growth plate cartilage dynamics and joint biomechanical functionality are intimately linked.

We will apply our new imaging methods to directly test our hypothesis in young, adult and aged OA-prone (STR/Ort mice) and healthy (CBA wild-type mice) intact joints. We will apply loads to murine knee joints and examine the subsequent strain patterns using our unique digital volume correlation code. We will then correlate these to hierarchical anatomical changes in joint structure, which we can now visualise at an unprecedented resolution. Next we will investigate the biomechanical and anatomical implications of microfractures in these joints. Finally, we will interrogate the MRC National Survey of health and development (NSHD) to determine if an association exists between the joint shape and life course longitudinal growth using previously derived measures of height size, tempo and velocity.

This work has the potential to improve human health by identifying those at risk of osteoarthritis and by identifying associated imaging biomarkers that predict OA onset and progression.