TAYLOR BOROWETZ

Researchers at the University of Saskatchewan have found key information illuminating what happens to human bone cells as we age.

Working with a team led by Canada Research Chair David Cooper, PhD graduate Yasmin Carter is exploring the difference in bone structures between the sexes and why osteoporosis disproportionately affects women.

The team’s specialty is bone imaging, the process of looking at 3-D micron-resolution images at the cellular level which works with the same principles as a CT scan.

Mechanosensation and mechanotransduction are two very technical terms that represent how bones sense loading, Carter said. For example, it can recognize how much you weigh, if you’re running or whether there is a bone injury such as a fracture.

Carter said that if a change in the system occurs, there is an alteration in its ability to respond to or sense damage. Both genders experience bone loss as they age, but for one in three women in Canada, it progresses further and leads to osteoporosis.

Osteoporosis results in many fractures and notably harms quality of life.

Carter was astounded to discover that hip fractures, a common injury with osteoporosis, in Saskatchewan cost the provincial healthcare system $25 million in 2007 alone.

With one in three women in the western world carrying this physical burden, the cost becomes huge.

The osteocyte system is the network of cellular spaces in bones. It may seem miniscule, Carter explains, but one millimeter of bone contains 30,000–40,000 cellular spaces.

“What we were interested in is whether or not we could see some differences in this cellular space system as women age,” she said.

She mentions that many groups are asking these questions, but have to base their studies on animal models whose systems simply do not have an adequately similar structure.

Both the bones in an animal and the stresses they undergo daily differ greatly from those of a human. Carter says the main issue they have is actually age-related. Shorter lifespan makes it very difficult to reproduce what an actual 80-year-old person might experience. For example, the average rat lives for two to three years.

She says the team is very lucky to have had access to the Melbourne Femur Collection, a collection of thighbones curated by a group of collaborators in Australia with per- mission from the next of kin.

The MFC provided the team with human samples. Carter explains that they’ve been able to look at a fairly significant number: 68 individuals, 30 of which were female.

The team did their preliminary work at the Advanced Photon Source outside of Chicago and have followed-up and tested it at the Canadian Light Source. Carter says their study would have been impossible without a synchrotron, as they allow you to see 3-D images of tiny samples in a non-destructive way.

All of their work has come to a surprising conclusion.

“We have identified a possible difference between the bones of men and women at this cellular spaces level,” Carter said.

There had to be some difference in functionality because of the bias osteoporosis has towards women, she continued, but no one has ever been able to find the right track.

Cellular spaces themselves are larger in young women and they become smaller with age. Carter explained that this is in contrast to those of a male, which stay basically the same size throughout their lifespan with minimal expected loss.

Because these bone spaces are initially approximately one-third larger in women, she speculated that there has to be a biological pressure for them to be larger.

Her theory is that this network of spaces can act as a storage system for minerals like calcium or phosphate that will be required to produce offspring later in life.

Carter said you theoretically can’t, especially in the past, eat enough minerals to support fetal development. Instead of doing this on demand, your system was always prepared for it.

Their hypothesis is that when a woman becomes pregnant, these stored minerals can be put to use. Now they have to work to prove it.

Another variable Carter would like to look at in their studies is whether or not the women sampled have had children. If their conclusion is true, the number of children a woman has had would undoubtedly affect her bone structure.

They also witnessed the cellular spaces becoming smaller in older women, which happens through a process called “infilling.” When infilling occurs, layers of minerals attach into the bone cell spaces.

The cells are connected together through tiny canals that are used to communicate between cells, acquire nutrients and allow the waste produced by the cells to be removed. She said the infilling may interrupt this system, which could reach a tipping point where portions of bone no longer have a functioning mechanotransduction system — the many processes by which cells convert mechanical stimulus into chemical activity.

This could be a possible reason for osteoporosis.

Carter said their next task is to go back to the cellular level to look at surrounding soft tissues and dig deeper into the effects of the infilling process. For this step, they will go back to work with confocal microscopy. She also hopes that they can identify specifically which materials are being filled in the cells.

The implications of this work could be quite vast. She questions why the osteocyte system operates the way it does, and whether infilling can be stopped.

To answer these queries, the team needs to sample more data throughout the age range and find when the infilling process starts to occur.

Their findings could greatly reduce suffering from age-related bone degradation.