Drug used to treat weak bones may reduce bone strength

1 March 2017

Bone samples

Micro-cracks inside bone samples from patients treated with bisphosphonate
(Credit: Diamond)

UK scientists have published startling new research which shows a type of drug used to treat weak bones may actually increase the risk of tiny cracks appearing in the bone.

The early-stage research, funded by STFC and carried out by scientists at Imperial College London, suggests these microcracks could make the bone weaker.

Researchers studied bone samples from 16 people who had been diagnosed with osteoporosis and had suffered a broken hip – but only half of the patients had been taking the commonly-prescribed drug bisphosphonate.

The team used X-rays from the UK’s synchrotron facility, Diamond Light Source, to visualize the structure of bone at a high resolution. They found that the bones of people taking the drugs not only had a larger number of tiny cracks, but also had less strength.

Osteoporosis causes bones to weaken, making them more fragile and prone to breaks. This is because the cells that help to regenerate old bone, called osteoclasts, become over-active and burrow holes, or perforations, into the bone.

The condition, which affects 3 million people in the UK and 200 million worldwide, usually strikes the over-65s.

Dr Richard Abel, lead author of the research from the Department of Surgery and Cancer at Imperial, explained: "This research suggests that, in a small number of patients, rather than protecting against fractures bisphosphonates may actually may make bones more fragile. We now urgently need larger studies to confirm this finding."

He added that further studies would also provide insight into whether there is an ideal length of time to prescribe the drugs.

Bisphosphonates slow the rate at which bone is broken down, by reducing osteoclast activity. These drugs, for which there are thought to be around 6.5 million prescriptions every year in the UK and 190 million globally, have been found to prevent the risk of fracture by 30-50 per cent.

But in recent years doctors have become increasingly concerned that osteoclasts are slowed to such an extent that in rare cases it may actually increase the risk of fracture.

This is because osteoclasts are needed to remove old, damaged bone so that it can be replaced with new bone. If these cells become too sluggish, bones aren’t regenerated or repaired as often as they should be – leaving them prone to damage.

To investigate this, researchers needed to analyse the microstructure of bone. This is not visible using standard X-ray equipment in labs or hospitals, so the researchers used Diamond to analyse the samples.

They studied eight hip bone samples from patients who had suffered a fracture while taking bisphosphonates, and eight samples from patients who had suffered a fracture but had not been taking the medication.

The team also studied samples from patients who did not have osteoporosis and had not experienced a hip fracture.

“It is great to see how our visualization tools have provided an insight into the microcracks” says Professor Laurent Chapon, Director of Physical Sciences at Diamond Light Source. “The X-rays used to map these cracks are usually used to help people to solve engineering or environmental problems, so it is good to see how physical sciences’ tools have benefitted medical research.”

The results revealed that the bones of people who had been taking bisphosphonates had 24 per cent more microcracks than the bones of people who had not been taking the drugs, and 54 per cent more than healthy ageing bone.

However, as expected, the bones of people who were taking bisphosphonates were also found to have fewer holes. Despite this, the bones from patients treated with bisphosphonates were also found to be 33 per cent weaker than the other osteoporosis patients who were not taking the medication.

Dr Abel went on to say: "There may be a crucial time point between holes in the bone being prevented, and microcracks beginning to form. If we can find this, we may be able to ensure bisphosphonates provide maximum protection against fractures by personalising the duration of treatment.

Long term we may need to develop other therapies that treat osteoporosis by building new bone rather than slowing the breakdown of old bone."

He said the team will now expand the field of study and investigate whether microcracks form in patients who have taken bisphosphonates but not sustained fractures.

Further information on the project can be seen here.

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Becky Parker
STFC Media Officer
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