New way to build stronger bones

American scientists have discovered a way to trigger bone production, raising hopes of a treatment for osteoporosis.

A team at the Howard Hughes Medical Institute found they could massively increase bone mass in mice by tweaking the structure of a protein in the body.

The modification is so minor they hope the side-effects will be minimal if the process is repeated in humans.

Osteoporosis, caused by thinning of the bones, affects about three million people in the UK.

It is estimated that it is responsible for 230,000 fractures suffered by Britons each year.

Details of the study were published in the journal Developmental Cell.

The results were dramatic, yet the molecular alteration is very, very minimal

Dr Gerald Crabtree

In vertebrates, bone is constantly being formed and broken down throughout life.

Cells called osteoclasts continuously degrade bone, while cells called osteoblasts replenish it.

Out of balance

In an ideal situation, the two types of cell are perfectly balanced, allowing the bone to maintain bone mass.

However, if the balance is upset and more bone is destroyed than formed it can lead to osteoporosis.

The researchers found that they could tip the balance by modifying the structure of a protein called NFATc1.

Their work was sparked by reports that patients who were treated with the immunosuppressant drug cyclosporine tended to lose bone mass.

Cyclosporine is known to trigger a change of shape - and function - in the NFATc family of proteins.

The researchers modified NFATc1 in mice so it could move more easily into the command centre of cells, and thus become a little more active than usual.

This triggered the production of large amounts of new bone.

Cell count up

Analysis showed that the animals' tissue contained increased numbers of both type of bone cell.

However, the increased production of osteoblasts was never quite matched by that of osteoclasts - and thus more bone is laid down, than is degraded.

The research suggested that NFATc1 stimulated production of osteoblasts, which in turn released inflammatory proteins called chemokines, which promote osteoclast development.

Researcher Dr Gerald Crabtree said it could potentially be possible to develop new drugs to treat osteoporosis by recreating the same effect.

They are hopeful that the risk of side-effects would be minimal, as only small modifications to NFATc1 were required to produce a profound effect.

NFATc1 in the mice that developed extra bone was only 10% more active than it is in normal mice.

Dr Crabtree said: "The results were dramatic, yet the molecular alteration is very, very minimal.

"If you could find a small molecule that would flip 10% of the existing NFATc1 into the active form you could favour the formation of osteoblasts and make stronger bones."

Pauline Davey, of the UK National Osteoporosis Society, said the condition had a major impact on NHS costs and the quality of patients' lives.

"Broken hips in particular cost the NHS and government £1.7bn a year to treat so finding effective drug treatments that reduce this burden is of great importance.

"There are a range of drug treatments which are effective but all drugs have side-effects which means some people can't get on with them.

"Therefore it's really important that there are other equally effective treatments that they can use."