Tough on the surface

Posted: 12th October 2017

Researchers from St Vincent’s Institute of Medical Research (SVI) in Melbourne have identified a key pathway that makes the external surface of male bones – called cortical bone – stronger than female bones.

Bone is made up of an internal honeycomb-like structure – called the trabecular bone – which is covered by a thick outer shell of hard cortical bone. While the signals between bone cells that control the growth of trabecular bone are relatively well understood, until this study, the signals that control cortical bone formation were unknown.

In research published in the journal Nature Communications, the team showed that mice lacking a signaling protein called Socs3 in specialized bone cells have severely delayed formation of their cortical bone. Male mice recover from this impairment at puberty, but female mice do not. This is because testosterone interacts with other proteins that enable the process of bone corticalisation to continue.

Treatments for osteoporosis are best at preventing vertebral fractures – the most common site of fracture. This is because they are able to increase the strength of the trabecular bone. However, these treatments are less able to strengthen cortical bone. Weakened cortical bone leads to fractures in the hip and wrist, which are common in sufferers of osteoporosis.

“Most research that has identified genes that control bone mass has focused on the trabecular bone,” said lead researcher, Associate Professor Natalie Sims. “Until now, we didn’t know any specific signals that control the strength of cortical bones, and why some people develop stronger cortical bones than others – it’s a big black box.”

“The next step is to identify which molecule needs Socs3 for cortical bone production. This could eventually lead to the development of treatments to slow the deterioration of cortical bone that happens with age and would aid sufferers of osteoporosis,” said Natalie.

“This discovery is very exciting as we have treatments that are reasonably good at preventing fractures in the vertebrae,” said Professor Peter Ebeling, Medical Director at Osteoporosis Australia. “However, we are not so good at fixing the more common hip and wrist fractures. If we can develop therapeutic targets that prevent the erosion of cortical bone, that could be a major game changer. It would have a huge impact on the quality of lives of many people who suffer from weak cortical bones and the cost savings to our health system would be significant.”

Funding for the research was provided by the National Health and Medical Research Council.

For more information please see: Bone cell biology and disease