Early diagnosis and intervention of osteoporosis using nanovibrational stimulation

Osteoporosis is a disease of the bone which affects 3M people in the UK, is associated with 300,000 fractures per year, and costs the NHS £1.9B/yr (figures provided by the National Osteoporosis Society, 2015). Current medical practice is to diagnose osteoporosis and provide pharmacological treatment only after a fragility fracture has occurred. This project seeks to revolutionise treatment through a drug-free, proactive management, through use of precision nanovibrational stimulation applied via bone conduction (similar to bone conduction headphones). Nanovibrational stimulation has recently been shown to produce osteoblasts (bone building cells) in the lab from mesenchymal stem cells (MSCs - adult stem cells found in the bone and elsewhere in the human body). This was the first time that osteogenesis (promotion of bone) has been observed in MSCs without the requirement for drugs and/or complex engineered scaffolds. Since osteoporosis has been linked to insufficient osteogenesis in MSCs, nanovibrational stimulation could provide a breakthrough route to decrease the onset, or perhaps even reverse the effects, of osteoporosis. In order to evaluate this in a timely manner, this project will study disuse-related osteoporosis (due to spinal injury) since this provides a time-accelerated model for testing interventions. The academic team will work alongside the clinicians within the Scottish Centre for Innovation in Spinal Cord Injury (SCISCI) in the Queen Elizabeth National Spinal Injuries Unit and conduct the first trials in nanovibrational stimulation for proactive treatment of osteoporosis.

The study aims to achieve early detection of the initial phases of bone loss, followed by preventative treatment intervention using nanovibrational stimuli, to slow/prevent osteoporosis disease progression and avoid fragility fractures (and morbidity and mortality associated with fractures). A key associated economic benefit of the proposed research is the reduction of healthcare costs associated with osteoporosis and fragility fractures, through effective preventative treatment of bone disease.

The route to clinical implementation will involve a phased approach. We will demonstrate the feasibility of early detection and diagnosis of bone loss/osteoporosis development and preventative treatment with the nanovibrational intervention in: (i) a pre-clinical rodent model of spinal cord injury (SCI), and (ii) a clinical population, in patients with SCI. Disuse-related bone loss after SCI is greatly accelerated, compared to postmenopausal osteoporosis or ageing-related bone loss. The impact of early detection and disease diagnosis, and the efficacy of preventative intervention can be demonstrated in a shorter timeframe in this patient cohort than in postmenopausal women (and the elderly, more generally) who typically exhibit much slower rates of bone loss.

Clinical application will be broadened to other populations that suffer bone loss and fractures (postmenopausal osteoporosis, frail elderly), and potentially even bone cancer treatment. The proposal therefore includes plans to apply for follow-on funding to ageing, osteoporosis and cancer charities (e.g. Age UK, NOS, CancerUK) to expand the reach. An additional group that could benefit from this research are astronauts on long-term space missions, who are susceptible to bone loss after exposure to a weightless environment. We will also explore funding opportunities through the UK Space Agency's calls on Human Factors and the Space Environment, to explore the use of nanovibrational intervention to maintain bone health in astronauts.

The Queen Elizabeth National Spinal Injuries Unit (QENSIU) represents a group of clinical end-users of the technology. With the QENSIU being a primary care and rehabilitation centre, the whole multi-disciplinary team at the spinal unit will provide clinical support for the researchers on the project (mainly for WP3), coordinated by Purcell - Research Lead and Spinal Consultant at the QENSIU. This support, combined with access to the research facilities that are embedded within the spinal unit (see Letter of Support), provides clear clinical translation pathways for the project. Patient and public involvement is provided through patient networks, initially focused locally with Spinal Injuries Scotland (www.sisonline.org), but as the project progresses, broadened out to include the the National Osteoporosis Society (www.nos.org.uk).

To communicate our research findings to the intended clinical beneficiaries and end-users, an Osteoporosis Awareness Day will be organised through the QENSIU, forpatients with SCI, their families and care providers, and patient support networks. This will be an opportunity for the researchers to discuss with key stakeholders the evidence-base for changing clinical practice in relation to osteoporosis treatment and management (SIGN guidelines in Scotland; NICE in rest of UK).

Dalby's lab have already reported that certain types of agressive bone cancer cells are adversely affected by nanoscale vibration at 1kHz, and therefore further clinical benefits may arise from this. Additionally, Dr Paul Brennan (Senior Clinical Lecturer and Honorary Consultant Neurosurgeon at the University of Edinburgh and NHS Lothian) has been provided a Nanokick bioreactor chemotherapy treatment protocols. Technology developed in this project would be highly applicable to these additional
clinical areas.

Reid has an industrial funded project with Linn Products, starting April 2018, developing thin film piezoelectric transducers.