PICUP - Point-of-Care Fracture Prediction

A significant and escalating worldwide health burden is the ageing population and its demand for accurate medical diagnostics. Of particular concern are osteo diseases such as osteoporosis (OP) as this results in a very high healthcare burden, particularly in elderly populations. More than 1000 people die every month in the UK from OP related hip fractures and the NHS costs associated with OP hip fracture are >£2.0b per annum.

This proposal concerns the development of a new clinical instrument to predict osteoporotic fractures within an individual and thus improve quality of life and reduce this health burden. The proposal, for the first time, will combine two recently developed technologies within a new, point-of-care clinical instrument. This proposal has been developed from a recently completed EPSRC research programme, "Point-of-Care High Accuracy Fracture Risk Prediction" (EP/K020196/1). This took the first research steps towards providing the underpinning science and engineering proof of principle for a new approach to fracture prediction. It was premised upon the thesis that bone is a complex engineering material where composition is critical to performance, i.e. osteoporotic compromise of fracture strength is related to changes in architecture, mass and material chemistry. The work also attempted to secure proof of principle for a new measurement technique (focal construct technology, FCT) that could derive critical chemistry features based upon X-ray scattering.

The research was a great success in that a new set of biomarkers, sensitive to osteoporosis, was discovered, and the novel data acquisition approach was demonstrated to provide the quantified parameters within the required precision. Other, smaller (short term) development research grants (IAA) awarded within the previous 18 months have also enabled us to explore options for alternative geometries and the use of other optical elements within the measurement space. Further, a current, joint STFC research programme (ST/N006526/1) is exploring the combined use of our FCT approach with a novel pixelated detector, Hexitec, albeit within a different application sector.

At this stage, the technological risks remain high, the demand for such research is tangible, and the potential societal and financial benefits are very large.

The programme will ultimately deliver a novel and accurate, non-invasive clinical instrument to assess bone quality and provide an individualised fracture risk prediction. Therefore, the ultimate beneficiary of this programme will be the aging general population who present with an increasing risk of fragility fracture. Currently, without the successful conclusion of this research, the management of osteoporosis sufferers is compromised by limited intelligence. Thus whether an individual needs "safeguarding" measures to minimise the risk of a fracture cannot be reliably determined. Equally importantly, the enhanced medical diagnostics afforded by this research will also prevent over safeguarding for those presenting with osteoporotic changed (as revealed by DXA) but mechanically robust bone.
The research programme is the second step (the first being the research that recognised new diagnostic markers) towards the development of the novel technology. The solution builds upon cutting edge science coupled with highly innovative state-of-the-art engineering. The application of the technology will enable patients to be accurately diagnosed within community environments. Our approach has the potential for wide spread impact in patient care, N.H.S. cost savings, U.K. industrial development and wealth generation. In particular the work will have impact for:

> Elderly populations, as individuals will be significantly less likely to suffer from factures (or even death following fracture) and thus have enhanced quality of life. The reduced times to receive any diagnosis will also relieve associated psychological stress.

> Patients receiving therapy for bone disease as this group will have improved care through faster and more accurate diagnostic testing.

> The N.H.S. as >£20 billion per annum is currently spent on treating hip fractures and this would be significantly reduced if accurate fracture assessment were possible. Further, rapid and more accurate diagnosis within the community would produce efficiency savings both for GP's and hospital clinicians.

> U.K. industry that will assume a world lead in this growing medical technology. This will underpin significant potential global R&D investment ultimately contributing to the U.K.'s economic growth. The clinical technology development will form part of what is planned to be a significant commercial commitment from Halo X-ray Technology Ltd (HXT) to this application area and thus will directly create new jobs and industrial activity. They intend to leverage the successful award of this grant to raise additional InnovateUK and private venture funding, which will be used to develop HXT presence and technology in the medical field. The development of new HXT products and the expansion into new markets will lead to greater support of local and national businesses. All HXT production is outsourced; increased sales will therefore boost all aspects of the company supply chain, including improved employment prospects within these companies. The export opportunity for new products based on this development will be significant and add substantially to the UK economy. In a similar commercial development, the work will significantly enhance the ability of the Science and Technology Funding Council to create licence agreements for its detector systems and thus offset the taxpayers contributions to scientific research within the U.K.

> The young scientists employed for the duration of the programme will benefit from training within an exciting and growing applied research field providing a springboard for future careers in academia and or industry.

> The Universities involved in the programme will benefit directly through an expanded research base, new collaborations and networks.