Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PoCOsteo (PoC in-office device for identifying individuals at high risk of Osteoporosis and osteoporotic fracture)

Teaser

Osteoporosis is the most frequently found metabolic bone disease and is characterized by low bone mass, micro-architectural bone deterioration, and increased bone fragility and fracture risk. It is no longer considered age or gender-dependent. About 28 million individuals...

Summary

Osteoporosis is the most frequently found metabolic bone disease and is characterized by low bone mass, micro-architectural bone deterioration, and increased bone fragility and fracture risk. It is no longer considered age or gender-dependent. About 28 million individuals (6.6% of men and 22.1% of women aged over 50) suffered from osteoporosis in the EU in 2010. About 8.9 million fractures occur annually worldwide, one third of which is experienced in the EU.

Early detection of individuals at risk of osteoporosis and starting a suitable treatment before the presentation of the complications would drastically improve the current situation.

Osteoporosis is a polygenic disorder, determined by the effects of several genes, with each gene separately having only relatively modest effects on bone mass and other determinants of fracture risk. Recent advances have suggested that profiling of genetic variations could not only identify those at high risk of developing osteoporosis but also enhance the predictive accuracy of fracture prognosis.

Also, in order to determine the effective onset of osteoporosis in an early stage in individuals predicted to be at risk, and to accurately monitor the evolution during treatment, the analysis of Bone Turnover Markers (BTMs) is emerging as a key route that could provide the required sensitivity/specificity. But although BTMs have shown clinically interesting associations with the rate of bone loss, the routine use of BTMs in clinical practice is complicated by large random within-patient variability (linked to diet, exercise, other medication etc.), and biologic variability (age, gender, body mass index, circadian, and menstrual variation).

The alternatives to BTM analysis such as DXA or ultrasonic measurements are expensive for smaller hospitals or private practices and/or lack sensitivity.

The early stage identification of high-risk individuals who would best benefit from intervention, and as a low cost in-office monitoring solution based on the measurement and accurate analysis of BTM values for patients with osteoporosis on treatment, are therefore two important gaps in the clinical armamentarium in osteoporosis management. However, with today’s technological advances, we believe it is possible to develop an in-office device capable of determining both the genetic predisposition and BTM values from a single drop of blood, at acceptable cost.

In order to develop such a device, various technologies including molecular medicine, nanobiotechnology, microfluidics, material sciences and biochemistry come together. While the proof of concept of different parts of the final device are already designed in the lab, their integration into a single device is still an idea and thus further tests are needed to confirm its accuracy for the final application.

The PoCOsteo project thus aims to integrate proteomics and genomics technology into a functional single PoC device and to validate the final instrument by comparing the results with that of the current state-of-the-art of each technology separately. The final device is aimed to be used by the physicians to identify individuals at high-risk of osteoporosis and osteoporotic fracture, to provide them with personalized care, and monitor the treatment process more efficiently.

In summary, the overall aim of PoCOsteo is the development, clinical validation and preparation for commercialisation of a Point-of-Care tool for bone disease (a.o. osteoporosis) prevention, detection and treatment.

Work performed

In order to have a framework of the musts and limitations for the final device, a list of all prerequisites that should be considered in the final device, both from end-costumers and regulatories point of view, along with the technological conditions for each partner was made.

The next step was developing the proteomic and genomic biosensors and corresponding microfluidic manifolds. The latter was designed in a way that the least amount of blood, collected through fingerprick, is needed. All the preparation steps of the sample are now designed to occur in the cartridge and tests are continued to reduce the measurement time, while increasing the shelf-life and accuracy of the sensors. The primary tests for both biosensors are promising and the challenges are being addressed.

At the same time, the final device is being designed to answer the needs of both biosensors in different steps of sample preparation, measurement and reporting. The idea is to have a portable and user-friendly device, and so all designs are made to fulfil these needs while not increasing the cost.

As the device will be tested in practice, two clinical studies have been designed and ethically approved. These studies are conducted in Austria, representative of European population, and Iran, representative of a middle-Eastern population. The participants are getting recruited and will be followed in the course of the project based on the submitted protocol. At the same time preliminary modeling simulations have been performed in order to have a better understanding of the needed variables and also the modeling techniques for the later phases.

Final results

With ageing society, osteoporosis is emerging as one of the main diseases that, indirectly via fractures, impacts significantly the quality of life on the one hand and healthcare expenses on the other. Because it is a ‘silent disease’ which really only manifests itself in the excessive consequences of a fall, both the diagnosis and compliance to therapy later on are problematic, contributing to a huge treatment gap and related costs both financially and in terms of quality of life. The only way to effectively change this situation is by providing the medical community with accurate diagnostic tools that are easily accessible and easy to use, provide immediate feedback, and are low-cost, both in terms of capex and opex. By combining in PoCOsteo a genomic and a proteomic assessment in one finger prick test, we will offer a unique tool which can in a single low-cost test make a convincing assessment of this important disease. This will allow the physician to immediately define follow-up actions with the patients, without having to schedule dedicated follow-up meetings which are costly and often lead to patient drop out.

The advanced requirements of the osteoporosis use case will drive a close collaboration between various players in the proposed value chain. The need to integrate all technology elements into a working set-up sufficiently advanced so that it can be used and evaluated during the project by non-technical people in medical labs, will require all parties to work together towards pragmatic and stable solutions, with commercial value that can be exploited also in other use cases after PoCOsteo. As such we expect PoCOsteo will lead to important new technology elements which will become commercially available.

Clinical validation in two hospitals will involve patients in the developments. Planned support and advise of the project by the International Osteoporosis Foundation, being the main global alliance of patient societies, research organizations, healthcare professionals and international companies working to promote bone, muscle and joint health, will ensure close follow-up and adjustment of regulatory issues, related to the project work plan and the later use of the PoCOsteo tool in realistic environments.

Website & more info

More info: http://www.pocosteo.eu.