Paget's disease - Causes of Paget's disease

Paget's disease is caused by abnormal bone regeneration, although it's not clear exactly why this happens.

Bone cells regenerate in a similar way to skin, so old bone is removed and replaced by new bone. This cycle is known as bone remodelling.

Two specialised cells are responsible for bone renewal and repair. These are known as:

• osteoclasts – cells that absorb old bones
• osteoblasts – cells that make new bone

In Paget's disease, something goes wrong with the osteoclast cells and they begin to absorb old bones at a much faster rate than normal.

The osteoblasts then attempt to produce new bone at a faster rate than normal. However, this means the new bone becomes weak, unstable and larger than normal over time.

Possible causes of Paget's disease

The exact cause of Paget's disease is unknown, but it's likely to be caused by a combination of genetic and environmental factors.

These are described below.

Genetic factors

People who inherit certain mutated genes from their parents have an increased chance of developing 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 that also increase the risk of Paget's disease substantially.

In about 10-15% 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 number of people affected by the disease has fallen sharply over the last 50 years in the UK. In contrast, the number of people affected in other countries has remained static, which indicates that environmental factors may play a role.

The severity of symptoms also seems to be decreasing. Up to 60 years ago it was not uncommon for people to experience severe symptoms in multiple bones, but this is no longer the case.

The reasons for these differences are unclear.

One theory is that Paget's disease might be caused by a slow-acting viral infection. Possible triggers include:

• measles virus
• canine distemper virus – responsible for a type of viral infection that affects animals, mainly dogs (distemper)
• respiratory syncytial virus (RSV) – which causes respiratory infections during childhood

As a result of vaccination programmes, both measles and distemper are now uncommon infections. This could account for the decrease in cases of Paget's disease.

Another theory suggests people with rural lifestyles may be at increased risk of developing Paget's disease. As the number of people living this type of lifestyle is now much less common, it could offer an alternative explanation for the fall in cases of Paget's disease.

Improvements in nutrition and a reduction in cases of rickets over the past 50 to 100 years have also been suggested as possibilities for the decreasing severity of Paget's disease.