Potential breakthrough for osteoporosis announced

Behind the Headlines

Monday June 15 2015

Losing bone is a normal part of the ageing process, but for some people it can lead to osteoporosis

Osteoporosis affects around three million people in the UK

"Bone could be regrown to treat osteoporosis after breakthrough," The Daily Telegraph reports. This headline follows the development of a new drug that may increase bone formation, which could potentially combat osteoporosis. But this has only been tested in the lab so far and has not yet been proven to work in humans.

The researchers took inspiration from a class of drugs called thiazolidinediones, which are used to treat type 2 diabetes by improving sensitivity to the hormone insulin.

A side effect of these types of drugs is they reduce the number of stem cells that turn into bone-producing cells. The researchers turned this side effect on its head by developing a drug that appears to have the opposite effect, increasing the number of stem cells that develop into bone-producing cells. Another potential positive is that these early results in mice suggest the drug does not appear to have a negative effect on insulin sensitivity.

The drug has so far been tested on human stem cells in the laboratory and in mice over 21 days to look for side effects. While it could potentially regrow bone lost through conditions such as osteoporosis, this has not yet been demonstrated. The drug increased the number of human cells that turned into bone-forming cells, but bone production was not assessed in the mice.

The researchers say their results are promising enough to commence further animal studies. This process takes time, and not all drugs get through these tests. If the drug does prove to be successful and safe enough in animal studies, it would then progress to human trials.  

Where did the story come from?

The study was carried out by researchers from the Scripps Research Institute in Florida and the University of Adelaide. It was funded by the US National Institutes of Health, the Abrams Charitable Trust, and the Klorfine Family Fellowship. The study was published in the peer-reviewed medical journal, Nature Communications.

The Daily Telegraph incorrectly reported that the drug "already exists, because it [is] used in the treatment of diabetes to regulate insulin production". This is not the case – the drug used to treat diabetes causes a reduction in bone formation. The drug in development has been designed to have the opposite effect.

The Telegraph also said the drug "increased the rate of bone grown in mice". While the researchers may now have progressed to testing this, it was not reported to be the case in this study. Even if these tests have now been done, they would not have undergone peer review and publication yet, so we can't judge how robust they are. 

What kind of research was this?

This was a combination of laboratory experiments on human stem cells in the laboratory and in mice.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a receptor present on stem cells, the immature cells from bone marrow that can become different types of cells.

Receptors are protein molecules that react to specific chemical signals, much in the way a lock can be opened by a key.

Stimulation of PPARγ causes the stem cells to turn into adipocytes (fat cells) rather than osteoblasts (the cells involved in bone formation).

A class of drugs called thiazolidinediones, or glitazones, target PPARγ to improve insulin sensitivity for people with type 2 diabetes. A side effect of this drug is that fewer osteoblasts are formed.

A chemical compound called SR1664 develops, which partially blocks the receptor, still improving the insulin sensitivity but without reducing the number of stem cells that turn into osteoblasts.

From this, the researchers have developed another chemical compound called SR2595, which stimulates the PPARγ receptor to have the opposite effect, causing the stem cells to turn into osteoblasts.  

What did the research involve?

The researchers carried out various experiments to look at the structure of PPARγ and how it interacts with SR1664. They used this information to help them design SR2595.

Human stem cells grown in the laboratory were exposed to SR2595, and researchers looked at whether this made the cells become bone-forming osteoblasts.

Mice were given the drug for 21 days to find out whether the SR2595 would worsen insulin sensitivity. The researchers assessed the level the drug reached in the mice's bodies and looked at their insulin sensitivity, as well as food consumption and body weight.  

What were the basic results?

The number of human stem cells that became osteoblasts increased when they were treated with SR2595 in the lab.

Mice given SR2595 did not have any change in insulin sensitivity, fasting insulin levels, food consumption or body weight. 

How did the researchers interpret the results?

The researchers concluded that the results on SR2595 were sufficient to now conduct further animal experiments. 

Conclusion

This research has shown that a new chemical compound called SR2595 appears to stimulate human stem cells in the laboratory to develop into bone-forming cells rather than fat cells.

It is not yet known whether this would occur in humans or other mice. Even if this is the case, it is also not known whether the increased numbers of bone-forming cells would have the desired effect of increasing bone growth for people with osteoporosis.

Early results from mice indicate the compound may not have a negative effect on insulin sensitivity, but this was only assessed over a period of 21 days in seven-week-old mice. Further animal studies of longer duration will be required to evaluate whether the drug works, and then whether it is safe.

While weakening of the bones is often an inevitable part of ageing, there are still steps you can take to improve your bone health. The recipe for strong bones is a healthy balanced diet that includes calcium, exposure to summer sunlight for most of our vitamin D, and regular exercise, as well as avoiding certain risk factors, such as smoking and too much alcohol.

Read more about bone health.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Bone could be regrown to treat osteoporosis after breakthrough. The Daily Telegraph, June 12 2015

New drug could help scientists to regrow bones meaning conditions such as osteoporosis could be treatable. Mail Online, June 13 2015

Links to the science

Marciano DP, Kuruvilla DS, Boregowda SV, et al. Pharmacological repression of PPARγ promotes osteogenesis. Nature Communications. Published online June 12 2015

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