Bone remodelling
To get a better understanding of how Paget’s disease affects your bones, it is useful to understand how your bones grow.
People assume that once their bones reach adult size, they remain static and unchanging. This is not so.
In much the same way as your skin, bone cells undergo a continuous cycle of regeneration, where old bone cells are removed and replaced by new ones. This cycle is known as bone remodelling.
Bone cells contain collagen, which is a type of protein that is very strong and robust.
There are two specialised cells that are responsible for regulating the collagen that is found in the bones:
- Osteoclasts are the cells that absorb the collagen from old bone cells.
- Osteoblasts are the cells that create new collagen to produce new bone cells.
In Paget’s disease, something goes wrong with the osteoclast cells and they begin to absorb collagen at a much faster rate than normal.
The osteoblasts will attempt to compensate for this by producing new collagen, but as they are working at a faster speed than normal, the collagen that they produce becomes weakened and unstable.
Over time, the disruption in the bone remodelling process can lead to your bones becoming bigger and weaker than usual.
Possible causes of Paget’s disease
The exact cause of Paget’s disease is unknown, but it is likely that the condition develops as result of a combination of genetic and environmental factors.
Genetic factors
There is evidence that people who inherit certain mutated genes from their parents – the RANKL mutated gene and the SQSTM1 mutated gene – have an increased risk of developing Paget’s disease.
There is also evidence that Paget’s disease can run in families. For example, an estimated 15% of people who have Paget’s disease have a close family member who also has the condition.
If you have a first degree relative with Paget’s disease, such as a parent, brother or sister, you are seven to eight times more likely to develop the condition.
Environmental factors
The evidence that environmental factors may play a role in Paget’s disease is based on the fact that the number of people who are affected by the condition has fallen sharply over the last 50 years.
If Paget’s disease was only caused by genetic mutations, the number of new cases that are recorded by the authorities each year would either stay relatively stable or would increase.
One suggested environmental factor is the measles virus. The theory is that the mutated genes, RANKL and SQSTM1, cause the measles virus to stay in the body after the initial measles infection has passed. The virus may lay dormant for many years before being ‘re-activated’ and attacking the osteoclast cells, causing them to malfunction.
Therefore, the fall in the number of cases of Paget’s disease could be because of a corresponding fall in the number of measles infections owing to the measles vaccination programmes.
At present, there is only limited evidence to support this theory. Further research is required in order to understand how environmental factors are linked to Paget’s disease.
