Another Reason to Consider Bone Quality, Not Just Density

Bone density has always been considered crucial to preventing fractures. But a University of Toronto researcher has found evidence adding to the increasing realization that bone quality may be at least as important as mass in preventing broken bones. 

Jane Mitchell, a professor in the Department of Pharmacology and Toxicology and her PhD student Lucia Zhang, discovered that the G protein, Gs, which is very important in developing bone, seems to create poor quality bone when it’s found in large amounts in the bones of mice. She published her results recently in the Journal of Bone and Mineral Research. Mitchell discussed the significance of her findings with writer Heidi Singer.

Tell me about your findings.

We’ve always assumed you have a certain amount of these G proteins in your cells and they’re going to be doing their job to convey signals. But we’ve assumed the amount of them doesn’t change. G proteins are in every cell in the body, helping to pass along signals from receptors that are stimulated by endocrine hormones and many neurotransmitters. There’s quite a range of functions of these G proteins – they regulate a lot of things in the body. We know that the Gs protein is particularly important in bone cells, because diseases where there is not enough Gs or where there is mutated Gs result in bone diseases. So we asked if increased amounts of normal Gs protein in bone cells in mice would have any effect. We saw lots of bone in these mice. What we didn’t expect was that the bone was full of holes. And this really decreased the quality of the bone: you could snap those bones much easier than regular bone.  

Could there be drugs that are increasing the numbers of G proteins and weakening people’s bones?

First, it’s important to say that these are mouse models, and we’ve made an extreme version so we can see the potential effect. We do know about diseases where the gene that codes for the Gs protein is mutated and that causes lots of bone problems, but those are relatively rare diseases. Is there something in between that may be going on with just normal G proteins?

We already know that some drugs, like glucocorticoids (a type of steroid), give you osteoporosis. And these drugs do change G protein levels. In fact, that’s why we set out to study the effects of increased G proteins in bone. Some other drugs do make bones weaker, but nobody has studied whether there are increases in G protein levels with these drugs, so we still don’t know if this is part of their effects on bone.  And some diseases make bones weaker too. For example, people with type 2 diabetes tend to be heavier so they have increased bone density but it’s not good-quality bone. We’re learning all the time that just measuring bone density is not telling the whole story.

How do we measure bone quality?

We look at the size of the bones but also if they are brittle or soft. These things can’t be seen on a normal bone density scan, which just measures the amount of bone mass, not the quality. Newer methods use microcomputed tomography that can tell you more about the bone quality but it’s an expensive method and not part of the standard of care right now. 

What’s the next step in your research?

We don’t know anything about why some people have higher levels of G proteins. I want to get a lot more human cells from a whole range of different people and see what’s the actual range of G protein expression and does it correlate to the quality of their bone? We are also testing if diabetes and drugs that affect bone density, are changing the levels of G proteins in the bone?