An x-ray of an osteoporotic patient.
An x-ray of an osteoporotic patient.
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"We need to help people start fighting osteoporosis before it’s even begun"

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"We need to help people start fighting osteoporosis before it’s even begun"

Melissa Formosa is unlocking new ways to predict and fight the onset of osteoporosis

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Right now, medicine is too dependent on radiographic imaging techniques for diagnosing osteoporosis. It can be a debilitating disease, one that develops slowly over several years, weakening bones and rendering them dangerously fragile. Such diagnostic radiographic tools have their own limitations, detecting osteoporosis only once it has already developed. This means that it is already too late to properly control it.

People tend to think of bones as static and unchanging, but this is a misconception. They are actually highly active organs, made of connective tissue reinforced with calcium and unique bone cells, with most also containing bone marrow where blood cells are made. Bone tissue is constantly turned-over throughout our lives, with these specialised cells absorbing the old tissue and laying down new tissue. These processes work hand in hand to maintain a healthy and strong skeleton.

The complex nature of bones means there are many different mechanisms by which osteoporosis can develop. Injuries from osteoporosis can be very painful and often debilitating, even requiring permanent hospital care in some cases, if someone breaks their back for example. The disease overwhelmingly affects older women: one in three women over the age of 50 are diagnosed with osteoporosis, whereas one in five men will suffer osteoporosis at the same point in their lives. Unfortunately, research into how and why the disease develops in some people is often overlooked by scientific research – but it’s becoming increasingly clear that osteoporosis has a significant genetic component.

For example, in the WNT1 gene (an osteoblast, or cell that creates bone), mutations disrupt the process of building bones so carriers have brittle bones and suffer from early onset osteoporosis. Findings such as these are important in demonstrating that osteoporosis is not – and can no longer be seen – as a disease that solely affects the elderly. 

"If we were able to fully understand genetic causes through AlphaFold, this could revolutionise treatment"

Yet, a fracture is still often the first indication that osteoporosis is present. What we need is to find biomarkers – a blood test or identified gene or protein we can seek out in those who are predisposed, or at high-risk of developing osteoporosis. We need to help people start fighting the disease before it’s even begun.

To help us do this, we’ve been using AlphaFold in an attempt to understand genetic causes more fully. Quite quickly we realised that this could revolutionise treatment, by way of using it to help develop personalised medicine; a model that aims to provide tailor-made prevention and treatment strategies for defined groups of individuals.

Someone with the disease could then have their genome sequenced and protein variants modelled. That would give us a better idea if that person is at risk of a fracture in the near future and, crucially, then take action to prevent that. It could also help us understand disease progression, and allow patients more control over deciding what intervention is best for them. Ultimately, the aim is to manage onset from the earliest possible stage, and prevent progression, fractures and the pain and debilitation they can bring.

When we enter the amino acid sequence into AlphaFold software, it creates a 3D image of what the protein structure looks like and allows us to compare the protein structures encoded by both normal and defective genes. With AlphaFold, we can visualise the impact of specific genetic mutations, some of which may only cause subtle structural changes. Others induce significant deformations to the protein, reducing its ability to function properly, contributing to disease.

Ultimately, we’re aiming to develop simple blood tests for young adults to help predict disease, and to find new genes and proteins associated with the disease so we can develop better drugs to treat it. Early detection and the introduction of personalised medicine could mean that osteoporosis can be managed much more effectively – and millions of lives could be vastly improved. 

This kind of AI is becoming more central to our work and will be central to that of future researchers in this field. We finally have a chance to get one step ahead of this debilitating disease – that’s priceless.