Researchers discover overlooked process of bone renewal

Small tunnels in the spongy (trabecular) part of the bone have been known for decades, but their role has remained unclear. Researchers from the Department of Clinical Research at the University of Southern Denmark, together with Danish and international colleagues from USA and Canada, now show that these tunnels are part of a process that renew trabecular bone from within.

In the hard outer layer of bone, researchers already know that similar tunnels form as part of the bone renewal process. The new study shows that a comparable renewal process also occurs within the small rods and plates of trabecular bone.

Bones require continuous maintenance

Bones are living tissue that is continuously renewed throughout life specialized bone cells remove old tissue, while other cells build new tissue in its place. The balance between breakdown and formation of bone changes with factors such as age, hormones and disease.

- Old bone tissue is continuously removed and replaced with new tissue. What is new is that we can see that this renewal can also take place within the small trabecular structures of the bone itself, says Lisbeth Koch Thomsen, visiting researcher and PhD from the Department of Clinical Research at the University of Southern Denmark and first author of the study.

Small tunnels revealed the full process

The tunnels themselves are not a new discovery. Previous research has mainly focused on the breakdown of bone tissue and has, among other things, associated the tunnels with disease and possible weakening of the bone structure.

In the new study, however, the researchers also identified the stages in which new bone tissue is formed, demonstrating that the tunnels are part of a renewal process from within.

The researchers were able to follow one tunnel in three dimensions through a series of very thin sections from a human bone sample. In different parts of the tunnel, they found evidence of bone breakdown followed by the formation of new bone tissue.

- We can see different stages of the same process. First, bone is removed, and then new bone is formed. This shows that the tunnels are not simply a sign of bone loss, says Lisbeth Koch Thomsen.

It is this link between breakdown and rebuilding that leads the researchers to describe the tunnels as part of bone remodelling.

Renewal within the bone structure

The already recognized bone renewal on the surface of trabecular bone does not necessarily reach older tissue deep within the trabecular bone. The newly described process may provide a way of reaching and renewing this tissue.

The researchers call the process intratrabecular remodelling. In the scientific paper, they propose that it can be regarded as a fifth mode of bone remodelling alongside four previously described modes.

One possible explanation is that the process helps replace older or microscopically damaged bone tissue deep within the bone structure. However, this remains a hypothesis and needs further investigation.

PTH increased the tunneling activity

A central part of the study is based on bone samples from people with hypoparathyroidism, a rare condition in which the body produces insufficient levels of the hormone PTH.

The samples were collected in an earlier randomised trial involving 62 participants, conducted by Professor Lars Rejnmark at Aarhus University Hospital. Participants received either PTH or placebo in addition to their usual treatment. The researchers have now analysed the samples to investigate intratrabecular remodelling.

After six months, the researchers found markedly more intratrabecular remodelling among participants who had received PTH. They observed both increased bone breakdown and subsequent formation of new bone tissue.

- PTH strongly increased intratrabecular remodelling. This shows that the process can be regulated, but we do not yet know what more or less activity means for bone health, says Lisbeth Koch Thomsen.

Rabbit model showed how the tunnels develop over time

Human bone samples can show different stages of the process, but they do not allow researchers to follow the same tunnel over time. In collaboration with Canadian colleagues, the researchers therefore used repeated 3D scans of the bone of a living rabbit treated with PTH.

By scanning the same area at two different time points, the researchers could see how the tunnels changed. Among other things, they observed tunnels moving towards each other and becoming connected.

This part of the study is based on a single rabbit and therefore cannot be directly extrapolated to humans. The research group is continuing to work with the model to investigate what controls intratrabecular remodelling.

The significance for bone health remains to be investigated

The study does not show whether the process makes human bones stronger or weaker. The researchers are now investigating whether it may, among other things, help replace older or damaged bone tissue deep within the bone structure.

- Until now, this process has been missing from our understanding of how bones are renewed. We therefore need to investigate its role in the normal maintenance of bone and whether it changes with age or disease, says Thomas Levin Andersen, Professor of Bone Pathology at the Department of Clinical Research at the University of Southern Denmark and Odense University Hospital and senior author of the study.

The study does not investigate osteoporosis treatment and cannot show whether the process could be used to prevent or treat the disease. Instead, the findings provide a basis for further research into the role of the process in humans.