The body’s fight against osteoporosis
Osteoporosis is one of the most common diseases in Norway. Researchers have now discovered that the body alters genes to counteract the disease.
40% of all women over the age of 50 will experience fractures as a result of osteoporosis. Many of these fractures could be avoided with better prevention and treatment. Illustration: colourbox.no
Osteoporosis (porous bones) is a disease that weakens the skeleton and causes bone fracture, even when there is no strain on the bone. However, new findings show that osteoporotic bones can fight back. The development of the disease is reduced through small chemical changes in DNA. In other words, the skeleton makes use of available mechanisms to slow down the disease.
The body cannot stop the disease on its own, but perhaps we can utilise the body’s own resistance to develop effective treatment.
Genes inhibit and stimulate bone formation
Our skeleton is continuously being broken down and reconstructed, and is entirely renewed over a ten-year period. This is referred to as bone remodelling. As we grow older a lack of Balance occurs in the remodelling process. Breakdown takes place faster than reconstruction, and the skeleton is weakened.
In normal remodelling some genes have the task of compensating for normal wear and tear by producing bone mass while others help to ensure that the remodelling is kept in balance by preventing an overproduction of bone. The various genes in our skeleton work in harmony to ensure optimal bone density.
Research conducted by Professor Emeritus Kaare M. Gautvik and his collaborating partners, Sjur Reppe and Vigdis Teig Gautvik, has revealed that one of the genes in this process – SOST – differs in women with osteoporosis. They have examined this gene in detail to find out why it is different in ailing women compared with healthy women in the same age group.
Chemical modification of DNA
Professor Emeritus Kaare M. Gautvik has discovered that the skeleton modifies genes to counteract weakness in the skeleton caused by osteoporosis. Photo: Carina V. S. Knudsen, UiO.
“Approximately 70% of our bone mass is genetically determined, while the remainder is based on other factors such as nutrition and lifestyle,” says Professor Gautvik.
In recent years he and his fellow researchers have identified eight genes that together can explain approximately 40% of the genetic variation in bone mass. Of these eight, the SOST gene that has attracted particular attention.
In the remodelling process the SOST gene produces a protein that slows down bone reconstruction. Researchers initially expected that the gene would contribute to a decline in bone mass in osteoporosis patients by making more protein. Instead, they were surprised to find that the SOST gene was less active in women with osteoporosis and consequently produced less of the inhibiting protein.
When the body is affected by osteoporosis, the gene that inhibits bone formation slows down in order to counteract the disease.
The mechanism behind the body’s own fight against osteoporosis is called epigenetics. Epigenetics entails that the DNA hereditary material is modified by enzymes by adding a chemical group. In contrast to a mutation where the building blocks of DNA are altered, epigenetics does not necessarily lead to a permanent change in DNA, but is an adaptation that ensures that the gene can function better in a new situation.
An overlooked disease
“Osteoporosis is primarily a women’s disease and has therefore been ‘overlooked’ by a male-dominated society and health service,” Gautvik asserts.
He is keen to draw attention to this overlooked disease.
According to the Norwegian Institute of Public Health, 40% of all women over the age of 50 will sustain a fracture as a result of osteoporosis. Fractures of the upper femur, the wrist and the back are common, and are often accompanied by serious complications and a lifelong reduction in functional ability.
In addition to considerable suffering for those affected, treatment and rehabilitation following fractures require the use of extensive public resources that could be reduced if the disease were diagnosed at an earlier stage, thus permitting better prevention and treatment.
A unique body of material
The research is based on a unique body of material. More than 300 post-menopausal women were given a medical examination, and 100 of these satisfied the inclusion criteria. Blood samples and bone samples were taken from all of these 100 women. The researchers used advanced biochemical and gene technology methods to analyse all the molecules formed in osteoporotic bones. These were then compared with healthy bones.
As a result the skeleton is the first of the human organs where we are familiar with the molecular composition underlying the construction. The results have been published and made available to all researchers who are interested in the function and diseases of the skeleton.
In addition, the blood samples from the women make it possible to detect substances in the blood – so-called biomarkers – that can give some indication of the state of the bones. One of the aims is to develop a new diagnostic test for osteoporosis in order to shed light on the risk of developing the disease.
“Knowledge of how the genes in the skeleton function during the disease can enable new approaches to treating the disease,” says Professor Gautvik.