Mechanical stimuli control bone development

September 2, 2013 by Simone Ulmer
Here, the 3D simulation depicts the stress on the bone tissue, calculated on the basis of CT images. The red areas represent high mechanical stress and bone formation while the blue ones represent low stress and bone resorption. Credit: Schulte et al. 2013

Researchers from ETH Zurich have successfully demonstrated, for the first time in vivo, how bone tissue responds to local mechanical stimuli that control bone formation. The study reveals how important it is to stimulate the bones through movement.

It is common knowledge that mechanical stress on bones, arising through activities such as jogging or walking, encourages bone formation. However, it has remained unclear how exactly the bone-forming cells in the bone marrow respond to – or how their bone-resorbing counterparts respond in the absence of strain. Now, researchers from ETH Zurich have demonstrated for the first time how local mechanical stress and bone formation or resorption () are linked by combining lab experiments and simulations on the CSCS supercomputer "Monte Rosa". These have revealed that eighty per cent of the build-up and breakdown of bone substance is controlled by mechanical stimuli.

Strain encourages balanced bone formation

The simulations reveal how the exerted locally in the lab – by stretching a vertebral body in a mouse tail – leads to the build-up of the bone substance in certain places and its resorption elsewhere. According to the researchers, the results also confirm the assumption that bone substance is formed where it is needed and resorbed where it is not. A well-balanced interplay between osteoblasts, which are responsible for bone formation, and , which resorb and break down bones, is important for a healthy organism. Both the over- and underproduction of these two kinds of cells lead to in the . "Our study is therefore essential for gaining a better understanding of bone diseases and how to develop new medications," says Ralph Müller, who is the study director and a professor of biomechanics at ETH Zurich.

The scientists used different groups of mice for their experiments. While a certain caudal vertebra segment was stressed mechanically three times a week for a period of four weeks in one group, this part of the experiment was omitted for the control group. Moreover, there was another test group in which the animals' ovaries were removed. The resulting lack of oestrogen has a negative impact on bone formation and leads to bone resorption – presumably one of the reasons why around thirty per cent of women develop osteoporosis after the menopause.

Experiment and simulation indicate correlation

During the experiments, the researchers regularly took high-resolution computed tomography images of the animals. Superimposed and processed into three-dimensional representations using imaging processing, the images produced spatial models displaying the areas of bone formation, bone resorption and areas where nothing had changed. The scientists then exposed these models virtually to different forces on the supercomputer and calculated what would happen next for every area. Through these simulations, the researchers were able to study the link between local and its impact on the bone at the cellular level. "The results clearly show that the activity of both the and the osteoclasts is controlled by mechanical strain," says Ralph Müller. "High local strains lead to the formation of the bone and low strains provoke its resorption." According to the researchers' analyses, the probability of bone substance being resorbed under increasing mechanical strain decreases exponentially while bone formation increases exponentially. Moreover, bone resorption appears to be controlled mechanically to a considerably higher degree than , especially in mice without ovaries, where non-specific bone resorption increases significantly in the absence of mechanical strain. In other words, bone substance is also resorbed in places where it is actually needed.

For the scientists, the results echo the mounting evidence that oestrogen receptors are involved in the bone-cell response to mechanical stimuli. In short: a lack of oestrogen receptors limits targeted resorption.

Explore further: Identification of a molecule linking bone loss and bone formation

More information: Schulte, F. et al. Local Local Mechanical Stimuli Regulate Formation and Resorption in Mice at the Tissue Level, PLOS One, 2013, 8(4): e62172. DOI: 10.1371/journal.pone.0062172

Related Stories

Identification of a molecule linking bone loss and bone formation

August 1, 2013
Bone integrity requires skeletal remodeling, which involves both bone formation and resorption. It has been previously shown that the formation of new bone is triggered by degradation of older bone. However, it is unknown ...

Reversal cells may tip the balance between bone formation and resorption in health and disease

June 6, 2013
By analyzing biopsy specimens from patients with postmenopausal osteoporosis and primary hyperparathyroidism, investigators have begun to pay increasing attention to "reversal cells," which prepare for bone formation during ...

Not only bone density, but also quality of bone predicts fracture risk

August 5, 2013
In a study carried out at the University of Eastern Finland, bone histomorphometry and infrared spectroscopy revealed abnormal bone properties in children with vertebral fractures and in children after solid organ transplantation. ...

New osteoporosis drug combination outperforms current alternatives

May 14, 2013
A combination of two FDA-approved osteoporosis drugs with different mechanisms of action was found to increase bone density better than treatment with either drug alone in a small clinical trial. As reported in paper receiving ...

Zoledronic acid linked to early increase in sclerostin levels

April 29, 2013
(HealthDay)—Women with postmenopausal osteoporosis treated with zoledronic acid show an early increase in serum levels of the negative regulator of bone formation, sclerostin, that return close to baseline after 360 days, ...

Mechanisms for a beneficial effect of moderate alcohol consumption on osteoporosis in women

August 2, 2012
Women after menopause tend to develop weaker bones from what is known as osteoporosis, which may lead to fractures (especially hip fractures) from falling. The weakness of the bones results from an imbalance between the normal ...

Recommended for you

New approach helps rodents with spinal cord injury breathe on their own

October 17, 2017
One of the most severe consequences of spinal cord injury in the neck is losing the ability to control the diaphragm and breathe on one's own. Now, investigators show for the first time in laboratory models that two different ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.

New method to measure how drugs interact

October 17, 2017
Cancer, HIV and tuberculosis are among the many serious diseases that are frequently treated with combinations of three or more drugs, over months or even years. Developing the most effective therapies for such diseases requires ...

A new compound targets energy generation, thereby killing metastatic cells

October 17, 2017
Cancer can most often be successfully treated when confined to one organ. But a greater challenge lies in treating cancer that has metastasized, or spread, from the primary tumor throughout the patient's body. Although immunotherapy ...

Research finds that zinc binding is vital for regulating pH levels in the brain

October 17, 2017
Researchers in Oslo, Norway, have discovered that zinc binding plays an important role in the sensing and regulation of pH in the human brain. The findings come as one of the first studies that directly link zinc binding ...

Researchers find factor that delays wound healing

October 17, 2017
New research carried out at The University of Manchester has identified a bacterium—normally present on the skin that causes poor wound healing in certain conditions.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.