Point-of-Care High Accuracy Fracture Risk Prediction

A significant and escalating worldwide health burden is the aging population and its demand for accurate medical diagnostics. Of particular concern are osteo diseases such as osteoporosis as these become significantly more apparent in elderly populations. Unfortunately, current diagnostic methods are poor predictors of pathology outcomes such as fracture risk. The challenge then is to identify and develop enhanced and new approaches to bone quality appraisal that can be employed for accurate prognosis, targeted therapies and therapy assessment.

It has been well demonstrated that 'bone quality' (including characteristics such as collagen/mineral ratio, collagen integrity, mineral crystallite size, microstrain) has a marked affect on a bone's mechanical properties and is probably the 'missing' information required to produce diagnostically predictive models of fracture. Unfortunately there is no current technique for its in vivo determination. However, such information is embodied within conventional X-ray scatter signatures (e.g. X-ray diffraction) although these are weak and present significant measurement difficulties.

We have identified a potential route to in vivo measurement of these clinically valuable but weak signals. The technology has only recently become available through independent innovations for (i) X-ray generation (flat panel/source-on-a-chip) and (ii) obtaining 'amplified' information from scattered X-rays (using 'focal construct technology', FCT). Critically, the multi-emitter flat panel X-ray source will enable us to engineer precisely the analytical X-ray beam required to provide scatter signatures enhanced by several orders of magnitude. The FCT beam topology also enables the simultaneous measurement of the absorbed X-rays (to estimate bone mineral density) and those coherently (and incoherently) scattered. The source-on-a-chip technology is manufactured as a flat-panel device capable of generating X-rays from very low-power sources. It has the additional advantage that it may be fabricated to produce an X-ray source of precisely the geoemetric form required for FCT. Ultimately we envisage these techniques being integrated within a single imaging/DEXA/scatter system to provide a comprehensive diagnostic tool. The nature of the techniques also enables design towards hand portable devices for point-of-patient care. Thus this proposal principally concerns the development of a new instrument that will be subsequently used to examine the possibilities of applying our novel technologies to a number of different areas and therefore it will enable a new and exciting research capability.

The research programme is the first step towards the development of a new healthcare technology for accurate and robust bone fracture prediction. The technological solution builds upon cutting edge science coupled with highly innovative state-of-the-art engineering. The application of the technology will enable patients with osteoporosis to be accurately diagnosed within GP surgeries and other local points of care. Our approach has the potential for wide spread impact in patient care, N.H.S. cost savings, U.K. industrial development and wealth generation.

1. Patients will be significantly less likely to suffer from factures (or even death following fracture) due to more informed patient management and will have enhanced health care through reduced times to receive the results of tests.

2. Patients receiving therapy for bone disease will have improved care through faster and more accurate diagnostic testing.

3. The N.H.S. spend of >£20 billion per annum on treating hip fractures would be significantly reduced if accurate fracture assessment were possible.

4. Industries in the U.K. will assume a world lead in the technology growth and application underpinning significant potential global R&D investment ultimately contributing to the U.K.'s economic growth.

5. The young scientists employed would be trained within an exciting applied research field providing a springboard for future careers in academia and or industry.

6. In the short term the Universities will benefit directly through an expanded research base, new collaborations and networks.