Population-level imaging, genomic and phenotypic analyses to determine how bone marrow adiposity impacts human health

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Stop and think about your bones: what images come to mind? Perhaps a skull with grinning jaws, or the strong white limbs stretching out towards your fingers and toes. You might even think of the bone marrow within them, producing the blood that courses through your veins. But this is not the whole picture, for your skeleton hides a secret: it is full of fat, and no one knows why.This unsolved mystery is surprising. Scientists first noticed that our bone marrow contains fat-storing cells, called adipocytes, over a century ago. Having fat in our bones might strike you as unusual, but it is not: in humans and other mammals, this bone marrow adipose tissue (BMAT) develops steadily after birth and accumulates rapidly during puberty. Indeed, by the time we reach adulthood BMAT can comprise up to 70% of bone marrow volume, representing almost 10% of our total fat stores. Therefore, it seems likely that BMAT plays some role in the normal functioning of our bodies.Recent studies suggest that BMAT may also influence numerous diseases. One way of measuring BMAT is by a technique called magnetic resonance imaging (MRI). MRI scans have shown that BMAT further increases with ageing and in many diseases. For example, BMAT often increases in osteoporosis, suggesting that it might contribute to the bone fragility that defines this disease. Increased BMAT also occurs in obesity and type 2 diabetes, metabolic diseases that are placing a huge burden on our society. Therefore, excessive BMAT may lead to poor metabolic health. Finally, BMAT might enhance the growth of tumours within the bone, such as those that have spread from breast or prostate cancers, as well as leukaemia and other cancers that begin in the bone marrow.Based on these findings, BMAT is now attracting considerable interest as a potential player in the development of numerous diseases. Unfortunately, study of BMAT has been relatively limited, and analysis of BMAT using MRI has never been done across large populations. Consequently, the roles of BMAT in normal physiology and disease remain poorly understood. So, what is the function of BMAT, and how might it impact human health?Our team of scientists from the Universities of Edinburgh, Westminster and Dundee is now working to answer these key questions. To do so, we will use information being collected by the UK Biobank, a major study that is following the health and wellbeing of 500,000 volunteers from across the UK. The UK Biobank is doing MRI scans of 100,000 participants, which is estimated to be completed before the end of our 3-year research project. Using this MRI data, we will measure BMAT in each participant. This will be done by using artificial intelligence techniques to create computer software for automatic analysis of the MRI scans. These approaches will establish how the amount of BMAT varies across this very large population. The power of the UK Biobank is that it has also collected DNA samples and health data on each participant. Therefore, once we have measured participants' BMAT we will be able to discover how this relates to other aspects of human health and disease. This includes physiological factors, such as age and sex; genetic factors, such as mutations in particular genes; and disease outcomes, such as heart disease, obesity, diabetes, osteoporosis, and many other conditions of ill health. Together, this unprecedented, large-scale research project will help to unravel the mystery of BMAT whilst also establishing new methods for automated MRI analysis. The latter will be of huge help to the NHS, which currently faces a major backlog of unanalysed MRI scans. More broadly, understanding the impact of BMAT on human health has great potential to improve diagnoses and treatment of numerous diseases, including osteoporosis, diabetes, cardiovascular disease and several types of cancer. This will be vital if we are to reduce the public health impact of these worldwide health problems.