Bone remodelling
To get a better understanding of how Paget’s disease affects your bones, it is useful to understand how they are kept healthy throughout life.
It is often assumed that once a person’s bones reach adult size, they do not change, but this is not the case.
In a similar way to skin, bone cells undergo a continuous cycle of regeneration, where old bone is removed and is replaced by new bone. This cycle is known as bone remodelling.
Bone is made up of a protein called collagen and a mineral called hydroxyapatite. Two specialised cells are responsible for bone renewal and repair. These are known as:
- osteoclasts – cells that absorb old bones
- osteoblasts – cells that lay down new bone
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 attempt to compensate for this by producing new bone, but because they have to work at a faster speed than normal, the bone that they produce becomes weak and unstable.
Over time, this disruption to the bone remodelling process can lead to bones becoming bigger and weaker than normal.
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.
These are described below.
Genetic factors
People who inherit certain mutated genes from their parents could go on to develop Paget's disease. The most important of these is a gene called SQSTM1. People with a mutation in this gene have a greatly increased risk of developing Paget’s disease in later life. Seven other genes have now been identified which also increase the risk of Paget’s disease substantially.
In about 15% of cases, Paget’s disease runs in families. If you have a close 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 in Britain and New Zealand. In contrast, the number of people affected in some other countries, such as Italy, has remained static.
The severity of symptoms also seems to be decreasing, as up to 60 years ago it was not uncommon for people to experience very severe symptoms in multiple bones. However, this is no longer the case.
The reasons for these differences are unclear.
In Britain, a possible reason for the decrease in the number of people who are affected by Paget’s disease might be the significant changes that have been seen in the ethnic mix of the population over the past 50 years. An influx of people from Asia and Africa, where Paget’s disease is rare, could account in part for the decreasing frequency of the disease.
Another theory is that Paget’s disease might be caused by a slow virus infection.
Viruses that have been suggested as possible triggers for Paget’s disease include:
- measles virus – a common childhood infection
- canine distemper virus – a virus that is responsible for distemper which is a type of viral infection that affects animals, mainly dogs
- respiratory syncitial virus – which causes respiratory infections during childhood
Due to vaccines, both measles and distemper are now uncommon infections. This could account for the decrease in cases of Paget's disease.
Another theory is that people with rural lifestyles, who regularly come into contact with farmyard animals, and who in the past had high levels of physical activity, may be at increased risk of developing Paget’s disease. As the number of people living this type of lifestyle is much less common than it was, it could offer an alternative explanation for the fall in cases of Paget’s disease.
Improvements in nutrition and a reduction in the occurrence of rickets (a bone disorder caused by a vitamin deficiency) over the past 50 to 100 years have also been suggested as possibly accounting for the decreasing severity of Paget’s disease.
