Why do we lose bone mass when we lose weight?

If the scale shows a lower number than usual when trodden, it can feel like a big victory. However, weight loss does not always happen without complications, because with weight loss, we humans also lose bone mass.

If you are already at risk of developing osteoporosis, or if you belong to the older part of the population, weight loss can therefore potentially lead to problems with the bones. A new research project, with support from Independent Research Fund Denmark, will try to find out why we lose bone mass when we lose weight.

»The idea is partly that we need to understand what happens in the skeleton during weight loss. Partly that we must try to find out how to prevent the amount of bone from decreasing when you lose weight,« says Morten Frost, Clinical Professor at Odense University Hospital and the University of Southern Denmark (SDU), who is leading the research.

The starting point for the research is the drug semaglutide, which is based on the hormone GLP-1. The drug can be prescribed in connection with type 2 diabetes or overweight, where it is essential for your health to reduce weight.

»The older you get, the worse you generally get at rebuilding your bones,« says Morten Frost and continues:

»You can't just say that older people shouldn't lose weight if they are overweight or obese. Because there are older people who have bad knees, a bad heart or other conditions suggesting that they may need help to lose weight. We must be able to help them to a slightly better weight loss, where the bone mass is preserved.«

Osteocytes control the process

In the body, there are cells called osteocytes, which are central to controlling the breakdown and building of our skeleton (see facts below).

The osteocytes are embedded in our bones and give a signal to the body when it is time to break down or build up bone mass.

In three sub-projects, the researchers are investigating how these signalling pathways work when losing weight is treated with medication based on GLP-1.

In the first part of the project, the researchers gave semaglutide to healthy people and at the same time had a control group that did not receive semaglutide. 

In both groups, bone tissue samples have been taken, and now the osteocytes will be examined for which signalling pathways they contain. And what differences there are in the signalling pathways of people who have lost weight compared to people who have not lost weight.

In the second sub-project, the researchers gave healthy people GLP-1-hormone for three days. Long enough for the body to detect the hormone, but for such a short time that the body does not have time to change weight.

»There we can look at the osteocytes and see if they look different and what activities there are in them. We can then compare this with the first sub-project, where people have lost weight. Then we can say whether it is determined by GLP-1 or whether it is due to the weight loss itself. We hope that this is due to the weight loss alone, because then the results of the studies could potentially also be relevant for other ways to lose weight. And then it will make more sense in the long term to develop a drug that works in different places in the signalling systems that cause changes in the bones during weight loss,« explains Morten Frost.

A stepping stone towards being able to slow down the degradation

In the third and final part of the project, the researchers are giving semaglutide to people with type 2 diabetes.

Type 2 diabetes affects bones in the way that the bone cells are less active, although science today does not fully know why. It may therefore be that weight loss has a different effect on the skeleton in type 2 diabetes.

Again, the osteocytes are studied by the researchers drilling a small amount of bone tissue out of the iliac crest.

All in all, the researchers hope to be able to find ways to slow down the breakdown of our bones when we lose weight. And whether it happens in the same way in people with type 2 diabetes.

»If we can find some targets in the degradation process, we may be able to help develop a drug that can protect the bones during weight loss. This is important for people who lose weight, but it could also be important for people who have osteoporosis who need to increase their bone mass. So, there are a number of potential gains. It's also a good thing if you lose weight in a healthier way in the future than you do today, where it's mostly just about getting rid of the excess body weight,« Morten Frost emphasises and adds:

»When you are overweight, you usually have a higher bone mass, and it may therefore very well be that the bone loss during weight loss in most people only normalises the amount of bone rather than causes low bone mass. However, we lack data on this. On the other hand, studies indicate that physical activity can help maintain some of the bone mass during weight loss. Exercise is also important for weight loss.«

The research project is planned to run over three years, and the project group includes Postdoc Eva M. Wölfel, PhD student Julie Bjerrelund and PhD Morten S. Hansen associated with the project.