DUBLIN, Ireland (Reuters) — Identifying tiny cracks in a person’s bones could act as an early warning sign for more serious degenerative bone diseases, according to researchers from Ireland.
Chemists from Trinity College Dublin, in collaboration with scientists from the Royal College of Surgeons in Ireland (RCSI), have developed a biologically safe ‘nanoagent’ that binds to the cracks in a bone, even if the crack is just a few microns in diameter – less than the width of a human hair. Using a powerful confocal fluorescence microscope, extremely high resolution 3D images can be produced to detect and quantify microdamage much earlier in order to diagnose skeletal diseases and combat their progression.
“At the moment we can measure the quantity of bone very well, but not its quality. We also have very good methods of treating people who are at risk of fragility fractures and osteoporosis, for example. But we don’t have a very good way of identifying who needs that treatment. So if we are able to measure bone quantity and bone quality we should get a better indicator of fracture risk and then be able to target our therapy at those people who most need it,” explained RCSI Professor of Anatomy, Clive Lee.
The technique, published recently in the journal Chem, attaches luminescent compounds to tiny gold structures to form a synthetic nanoagent. When a microcrack is formed in a bone, calcium is exposed at that specific site — with the nanoagnet designed to be attracted to this exposed calcium.
The study was led by Professor of Chemistry, Thorri Gunnlaugsson, and postdoctoral researcher, Esther Surender. In laboratory tests, to simulate the microcracks they used a scalpel to score bone samples. This was then dipped into the nanoagent.
“To mimic damage to a bone, what we’ve done is generate a scratch by using the scalpel and then we put our bone into the agent which we have here in the solution. We can clean it up, leave it here for a certain amount of time up to several hours or only a few minutes, and we can rinse it and put it back into this dish and this is what we image then underneath the confocal fluorescence microscope,” said Gunnlaugsson.
While lab-based trials exposed bone samples to the nanoagent in a petri dish, real-world application would most likely have the agent injected into the blood stream in vivo at the site of the area under scrutiny.
Crucially, the technique does not expose the patients to X-rays which emit radiation and have, in some cases, been associated with an increased risk of cancer.
“Unlike x-ray where you will see the whole body imaging here we are targeting only the cracks in the bone, only the damaged area. And that’s the advantage of this technology,” added Gunnlaugsson.
The scientists concede that while the procedure works in the lab using bone samples, it cannot yet be implemented in the real world. They envision it will one day be possible to use their it alongside MRI scanning (magnetic resonance imaging), which uses harmless, non-ionizing radiation. Current MRI machines, however, lack the sensitivity and resolution needed to identify the tiny microcracks once the nanoagent has been administered. In effect, they’re now waiting for MRI technologies to catch up.
Nevertheless, the researchers say their nanoagent has great potential for catching stress or fragility fractures before they become more serious.
In elderly people with osteoporosis, bones are so weak and brittle that a fall – or even a sudden coughing fit or strenuous bend – can cause a fracture. But diagnosing weak bones before they break could reduce the need for operations and implants.
“If you break your hip, at the moment you’ve got about a 50 percent chance of not being able to live independently again and about a 20 percent chance of dying within six months. If we could identify the people who are most at risk for getting hip fracture, we could treat them and so prevent that fracture happening,” said Lee.