Paget's Disease

Paget’s disease of the bone – What is Paget’s disease of the bone?

Paget’s disease of the bone is a chronic ailment affecting the skeleton. Sir James Paget described Paget's disease of bone in 1877 and the disease is named after him.

Who does Paget’s disease of the bone affect?

This is a rare disease affecting 1% of the population in the United States. It commonly affects the elderly and nearly 3 to 4% of the population over age 50 are affected.

The disease commonly affects men more than women (3 men for every 2 women affected). (1-7)

What regions are affected by Paget’s disease of the bone?

Paget’s disease affects almost any bone in the skeleton but is commonest in the spine or vertebrae, pelvis or hip bones, long bones of the arms and legs and the skull.

The disease may be restricted to one bone or may affect more than one. It can affect the entire bone or a part of it.

Inheritance of Paget’s disease of the bone

The condition runs in the families and can be inherited. It can be present in as many as 25 percent to 40 percent of the direct descendants of someone with the disease.

The disease appears frequently among those of Anglo-Saxon descent and those who live in certain geographic areas, such as:

  • England
  • United States
  • Australia
  • New Zealand
  • Western Europe

Paget’s disease is uncommon in:

  • China
  • Japan
  • Scandinavia
  • India

It is very rare among other ethnic groups, such as Asians and Africans.

Causes of Paget’s disease of the bone

There is a marked variation in the number of cases of Paget’s disease in different regions of Britain. For example, the condition is less common in the south of the country, (estimated 1 in 100 people over the age of 55 is affected), and it is more common in the north, (county of Lancashire where 1 in 50 people over 55 may be affected).

This fact suggests that both environmental factors as well as genes may play a role in the development of Paget's disease. The exact cause is unclear.

Symptoms of Paget’s disease of the bone

The condition leads to enlarged and deformed bones. There is pathological breakdown of the bone cells. This is followed by excessive bone formation and repair that makes the bone dense but brittle.

Normally, as people age, their bones rebuild at a slower rate. For those with Paget's disease, however, this process of rebuilding and repair of bones takes place at a faster rate.

The most common symptom is bone pain. There may be recurrent fractures, joint pain or arthritis, bowing or bending of the legs, loss of hearing if the skull is affected, pinching of vital nerves leading to pain and other symptoms. Symptoms get worse slowly, and the disease does not spread to other bones.

Diagnosis of Paget’s disease of the bone

Paget’s disease is diagnosed in those over 40. Diagnosis is based on X ray features of the affected bones. Blood tests show a rise in serum alkaline phosphatase that reflects new bone formation.

Urine test results also indicate rapid bone formation. A bone scan usually shows the extent of involvement of the disease.

If bone cancer is suspected bone biopsy may be advised where samples of the affected bones are viewed under the microscope for signs of cancer.

Treatment of Paget’s disease of the bone

Medical therapies aim to reduce the frequency of pain, fractures and arthritis. Effective and safe treatment methods can help most people with Paget's disease.

Prevention of Paget’s disease of the bone

There are no known ways to prevent Paget's disease. A healthy diet rich in calcium and Vitamin D and regular physical exercise is important in maintenance of normal bone health and joint mobility.

Causes of Paget’s disease of the bone

Paget’s disease is a rare disorder of the bone affecting the rate of formation and destruction of various bones of the skeleton. It is common in the elderly and those from European descent. The exact causes of this condition are unclear. (1-6)

Physiology of the bone

Normally a bone breaks down regularly with use and aging. As a result of this breakdown in the younger individuals there is normal bone repair and growth that is called remodelling and takes place every day.

Cells that breakdown or absorb and dissolve bone cells are called osteoclasts and those that form new bone cells are called osteoblasts. The rest of the bone is made up of a protein called collagen and a mineral called hydroxyapatite.

Pathophysiology of Paget’s disease

In Paget's disease the osteoclasts become more active than the osteoblasts creating a discrepancy between bone breakdown and formation. This means that there is more bone breakdown than usual.

The osteoblasts try to keep up by making new bone. The whole process becomes chaotic leading to formation of deformed bones that are large, misshapen, and dense, while all the while weak and brittle and easy to fracture or bowing or bending due to pressure. The bone is deformed, and fits together haphazardly.

A normal bone when viewed under the microscope shows a tight overlapping structure that appears as a brick wall. In Paget’s disease there is an irregular mosaic pattern, as though the bricks were just gathered and left together haphazardly.

Cause of Paget’s disease

The cause of Paget's disease is unknown. Genetics play an important role in development of this disease. This is evident because people of the Anglo Saxon descent are more at risk of this condition.

Similarly those of African or Asian origin rarely are affected by Paget’s disease. Thus Paget's disease occurs more commonly in European populations and their descendants.

Genes are said to be activated when exposure to a virus. It may be present in as many as 25 percent to 40 percent of the direct descendants of someone with the disease.

Genetics of Paget’s disease

The inheritance is said to be Autosomal dominant. There are four to seven genes that when faulty cause Paget's disease. Of these a special gene mutation or variation called the sequestosome 1 (SQSTM1) is the most important.

Patients carrying this mutation seem to be severely affected by Paget's disease and there is a high risk of transmitting the infection in offspring. The disease commonly affects elderly and men are slightly more at risk of the disease than women (3 men affected for every 2 women with the condition).

Environmental causes of Paget’s disease

Environmental conditions are also responsible for causation of this disease. This is evident by the fact that those who live in certain geographic areas, like Northern and western Europe, the United States, Australia and New Zealand are more at risk.

Paget’s disease is uncommon in those living in China, Japan, Scandinavia and India.

There is also a marked variation in the number of cases of Paget’s disease in different regions of Britain. For example, the condition is less common in the south of the country, (estimated 1 in 100 people over the age of 55 is affected), and it is more common in the north, (county of Lancashire where 1 in 50 people over 55 may be affected).

The number of people affected in Britain is on the decline since due to immigration of people of African and Asian origin there is an ethnic mix of people who do not get this disease. However, the disease remains the commonest in the UK with over 1 million affected patients.

Other causes of Paget’s disease

Mechanical stress may play a role in causation of Paget’s disease. Some researchers suggest the infections with the following viruses may be possible triggers for Paget’s disease:-

  • Paramyxovirus including measles,
  • canine distemper virus affecting dogs primarily
  • respiratory syncytial virus affecting babies

This however is not proven.

Due to vaccines, both measles and distemper are now uncommon infections. This could also account for the decrease in cases of Paget's disease.

Symptoms of Paget’s disease of the bone

Paget’s disease is a rare bone disease that is characterized by enlarged, deformed and brittle bones that easily fracture. The disease is thought to be inherited with several genes leading to increased susceptibility.

Paget’s disease commonly affects the elderly and is more common in men than women. People of the Anglo Saxon descent are more prone to this condition while people from African or Asian origin are least at risk.

Symptoms of the condition can be outlined as follows (1-6):

No symptoms of the disease

In many patients there may not be any symptom of the condition. In these patients a routine X ray or blood test for another condition may reveal the disease as a chance finding.

Age and sex

Normally the disease is diagnosed in people over the age of 40. Men are a little more commonly affected than women. For every 3 men diagnosed with the condition there are 2 women affected.

Bones affected

Bones affected commonly are the spine or vertebrae, skull, long bones of the arms and legs and the pelvis or the hip bones. In one third of cases the disease is monostotic and affects a single bone and in two third of the cases the disease is polyostotic and affects two or more bones.

Bone pain

This is the most common symptom of Paget’s disease. The pain is due to rapid formation of new bone that may lead to bone fractures or pinching of vital surrounding nerves. Pain may be present at rest, at night and on movement but does not tend to be focused around a particular nearby joint.

Bone fracture

Recurrent and easy fracture of the bones that are affected. Due to repeated breakdown and remodelling of the bones they are liable to fractures that are caused even with minor trauma or injury.

Bone deformity

Bone deformity can be caused by enlarged and hyperactive bone formation. This affects the surrounding structures like nerves etc. leading to pain.

Compression of the nearby nerves may also lead to paralysis or numbing of sensation of the nearby regions. For example affliction of spine and pelvis leads to sciatica and those from the neck and arms leads to cervical radiculopathy.

Bowing of the legs

Due to weak and soft bones of the legs, weight bearing may lead to bowing or bending of the legs.

Joint pain

Joints near the affected bone are painful with arthritis. This may hamper joint mobility.

Hearing loss

There may be hearing loss if the bones of the skull are affected. Normally hearing takes the help of conducting sound waves and vibrations via tiny bones inside the ear.

When the skull is affected hearing mechanism may be hampered. There may be symptoms of tinnitus or ringing of the ears as well.

Headaches

In addition there may be headaches if the skull is involved due to pressure on nerves and blood vessels. Some patients also develop a larger size of the head.

Skin temperature

Skin temperature may be increased over areas of active disease or the affected bones.

Heavy bleeding

Bones that have a high blood supply may also lead to heavy bleeding if affected. Due to high blood supply to these bones the heart may develop heart failure due to its inability to pump blood.

Excessive calcium in the bloodstream

Excessive Calcium from bone breakdown is released into the blood stream. This leads to features such as weakness, fatigue, loss of appetite, constipation and abdominal pain. The heart pumps in more blood to the affected bone compared to normal.

Paralysis of limbs

There may be paralysis of one or more limbs if the spine is affected.

Paget’s disease and bone cancer

If the pain is severe and uncontrolled with medication the disease may have degenerated into a bone cancer. This is called Paget's sarcoma occurs in only about 1 percent of patients with Paget's disease. If affects patients with Paget’s disease over 70 years of age.

Progression of symptoms

Symptoms get worse slowly, and the disease does not spread to other bones.

Diagnosis of Paget’s disease of the bone

Paget’s disease of the bone is a rare condition affecting the elderly and it primarily involves a faulty bone metabolism.

Diagnosis of this condition is usually made in individuals over 40. It is rare in younger individuals.

Diagnosis of the condition may involve X-rays, blood tests and so forth.

X-rays to diagnose Paget’s disease

In some patients there may be no symptoms of the condition. Diagnosis in them is made by chance on X ray of the affected joint or on routine blood tests.

In early stages of the disease more bone is broken down and the bone may appear as riddled with black holes on X rays.

Later in the disease process these black areas can take the shape of a "V," with denser, thicker bone following behind it. This is known as 'the blade of grass' lesion.

The 'cotton wool' pattern in the skull is also characteristic where several woolly patches are seen over the skull on X ray.

On X rays the affected bone shows up as large, dense white and deformed. The shape may be bent or bowed seen in the long bones of the limbs. There may be evidence of a fracture in the bone as well.

Blood tests to diagnose Paget’s disease

Blood tests include those for serum alkaline phosphatase. This enzyme measures the bone turnover. It is usually quite elevated in patients with Paget's disease.

Usually blood levels of calcium, phosphorus, and parathyroid hormone are normal but prolonged immobility may lead to raised levels of blood calcium.

Urine tests to diagnose Paget’s disease

Urine tests also show signs of excess Calcium and rapid bone turnover. Urine levels of deoxypyridinoline and N-telopeptide are elevated.

Non-isomerised C-telopeptide fragments are also monitored to provide clues regarding disease activity and progression as well as treatment efficacy.

Bone scan to diagnose Paget’s disease

A bone scan or a PET (Positron Emission tomography) scan is advised for patients with Paget’s disease. In this test, a radioactive material is injected into a vein and it reaches all blood vessels of the body including those within the bones.

A special camera is used to look through the whole skeleton for areas or “hot spots” where the radioactive dye concentrates. These are areas of more bone turnover than usual.

Paget's disease almost always looks “hot” and active on a bone scan. As the disease progresses over a long time the spots area “burned out.”

Biopsy to diagnose Paget’s disease

Bone samples may sometimes be needed for biopsy. It is important to confirm the diagnosis of Paget’s disease. This test is advised before starting therapy to exclude other pathologies like:

  • osteoporosis (bones becoming brittle with aging)
  • osteoarthritis
  • osteomalacia
  • metastatic or cancer of other organs (e.g. breast or lungs) spreading to the bones

Biopsy is also advised to exclude bone cancers. These biopsies are sometimes done with a needle to take a sample of the bone. The local area is numbed prior to insertion of the needle. Sometimes the biopsies may be performed using small incisions in the operating room.

Hearing tests to diagnose Paget’s disease

Hearing loss may be the first to be detected in Paget’s disease affecting the skull bones. Here various audiometry and hearing tests are performed to detect if hearing loss is due to nerve affliction or due to bone deformities. A CT scan or MRI of the skull may be advised.

Heart failure

Heart failure is detected in severe Paget’s disease.

Imaging studies to diagnose Paget’s disease

Due to high blood levels of Calcium from increased bone breakdown kidney stones may occur. These are detected by imaging studies like Ultrasound and X rays. (1-5)