The information in each section below explains what Paget's disease is, how it is diagnosed and discusses causes, symptoms and complications. See the Treatment section for information on the treatment and interventions which may be used.
- What is Paget's disease of bone?
Paget’s disease is the second most common metabolic bone disease after osteoporosis. Approximately 1% of people in the UK, over the age of 55 years, are thought to be affected. The condition is also common in other European countries such as France, Spain and Italy and in people of European descent who have emigrated to other regions of the world, such as Australia, New Zealand, the United States of America and Canada.
Paget’s disease is a metabolic bone disorder in which the normal repair and renewal process within bone is disrupted. Bone affected by Paget's disease is renewed and repaired at an increased rate, causing abnormalities in the bone’s structure. Pagetic bone can appear enlarged and misshapen. Paget’s disease often causes no symptoms and may be found by chance. For those with symptoms, these may include pain, deformity and fracture. Either single or multiple bones may be affected with common sites being the spine, skull, pelvis and thigh (femur).
- How does Paget’s disease affect bone?
Bone is an active living tissue that is constantly being renewed through a process known as remodelling. Cells called osteoclasts break down old, damaged bone to make way for new bone laid down by cells called osteoblasts. Over time, this bone is mineralised, forming a hard and strong skeleton. Under normal circumstances, the amount of bone removed is balanced by the amount of bone laid down. In Paget’s disease, the processes of bone resorption and bone formation are markedly increased. The osteoclasts are larger than normal and break down bone faster than normal. The osteoblasts respond to this by depositing new bone at an increased rate. This dysregulation of bone turnover in Paget’s disease results in abnormalities of the bone structure, weakening of the bone and enlargement or deformity of the affected bones. Pagetic bone often appears misshapen and enlarged. You can learn more by watching this video on our Youtube channel.
- What causes Paget’s disease?
There are still some uncertainties about the causes of Paget’s disease, but it is generally believed to be due to a combination of genetic and environmental influences.
Genetic factors play a key role in predisposing to Paget's disease. It is thought that people who develop Paget’s disease inherit variations in one or more genes that regulate osteoclast activity, causing bone resorption to be increased. This is thought to be responsible for the increased bone remodelling that is typical of the disease. The most important predisposing gene for Paget’s is called Sequestosome 1 (SQSTM1). Abnormalities of SQSTM1 have been identified in 40% to 50% of people with a family history of Paget's disease and also in 5% to 10% of people who have no family history. The children of people with Paget’s disease are about seven times more likely to develop Paget’s disease than people who don’t have a family history.
Environmental factors also play a role in Paget’s disease, as evidenced by the fact, that over the last few decades, the frequency and severity of the disease have declined in many countries, and is most marked in regions that previously had a high prevalence, such as the UK. Various environmental triggers have been suggested, including dietary calcium or vitamin D deficiency, exposure to environmental toxins, repetitive mechanical stress on the bone, skeletal trauma and slow viral infections. Despite this, researchers have yet to discover which environmental factors influence the development of Paget’s disease.
- What are the symptoms?
The symptoms of Paget’s disease vary widely. Many people who have Paget’s disease do not have symptoms and never develop complications. In many cases, individuals are unaware that they have the condition. It may be discovered by chance on x-ray or if a blood test is performed for another reason.
Of those who present with symptoms, pain is the most common. Pain may arise from the affected bone itself, or from the altered biomechanics of limb deformity; for example, a bowed leg alters the way you walk and puts stress on the joints and soft tissues.
The blood flow to active areas of Paget’s disease increases and this can lead to a feeling of warmth over the affected bone. The affected bone may become enlarged and misshapen.
In many cases there may be no symptoms and individuals are unaware that they have Paget’s disease.
Further information can be found in our Booklets and Newsletters in the Member's Area of this website.
- How is Paget’s disease diagnosed?
It has been estimated that less than 10% of patients with x-ray evidence of Paget’s disease come to medical attention. When Paget's disease is suspected, a full assessment by a hospital consultant is recommended to determine if treatment is required.
Paget's disease may be identified by an x-ray, blood test or bone scan.
In many cases, Paget’s disease is found by chance when tests are carried out for another reason.
A common blood test in general practice is to measure liver function. Included in this test is an enzyme called alkaline phosphatase (ALP). This is present in many cells within the body, but particularly in liver and bone cells (osteoblasts). If there is overactivity of the osteoblasts due to Paget’s disease, alkaline phosphatase is released into the bloodstream and can be measured.
When Paget’s disease is active, the ALP level will often, but not always, be raised. A raised ALP can stand out as being the only abnormal result. If there is co-existent liver disease, it may be necessary to perform further blood tests to identify the source of the elevated ALP.
Serum total alkaline phosphatase (ALP) is recommended as the first line blood test, in combination with liver function tests to detect Paget’s disease. If the total ALP values are normal and clinical suspicion of Paget’s disease is high, then measurement of more specialised tests such as bone alkaline phosphatase (BALP) or N-terminal propeptide of type I procollagen (P1NP) may be required.
Log-in to read Professor Fraser's article on Blood tests in Paget’s Disease of Bone, which you will find under Information in the Member's Area.
When an x-ray is taken of a bone affected by Paget’s disease, characteristic features can often be seen (figure 7).
Research has shown that plain x-rays targeted to several sites, the abdomen, skull and facial bones, and both tibiae (shins), are likely to detect 93% of bones affected by Paget’s disease, compared with a single x-ray of the abdomen, which detected less (79%).
A single x-ray cannot give any information about other bones which may be affected. A radionuclide bone scan, as described below, is the best way of fully evaluating the extent of Paget’s disease.
- Bone scan
There are two types of bone scan in common use. Dual-energy x-ray absorptiometry (DEXA) scans, which are used in the diagnosis of osteoporosis, and radionuclide bone scans, used in the diagnosis of other bone conditions.
Radionuclide bone scans, also known as scintigrams, isotope bone scans or nuclear medicine bone scans, are the most helpful in Paget’s disease. A scan is recommended to determine which bones have Paget’s disease and how active the disease is. The radionuclide scan involves the use of a small amount of a radioactive tracer, which is injected into a vein in the arm. After some time, the tracer collects in the bones and pictures can be taken by a scanner (gamma camera). Information sheet (PDF): Isotope Bone Scans
A bone biopsy is a procedure in which a small sample of bone is taken and examined under a microscope. This is seldom required but can be useful if there is uncertainty about the diagnosis.
- What are the possible complications?
The potential for complications will depend on which bones are affected by Paget’s disease. Complications may require medical or surgical intervention.
Examples of complications arising from the involvement of specific bones:
- Skull. Paget's in the skull can cause headaches, hearing loss, ringing in the ears and a change in shape and/or size of the skull (i.e. enlarged head, wide forehead).
- Spine. Paget's in the spine can lead the affected vertebrae to become enlarged and deformed which can cause curvature of the spine, pain, and pressure on nerve roots with tingling, weakness and numbness in the legs.
- Femur. Paget's in the femur (thigh) can cause local pain at the site of the Paget's disease or related to osteoarthritis of the hip joint. Fissure (partial) fractures in the bone may lead to a complete fracture.
- Pelvis. Paget's in the pelvis may be painful and accelerate osteoarthritis in the hip joint.
- Shin. When the lower leg is affected the bone may feel warm, be painful and it may bow. Osteoarthritis may develop in the knee joint and fissure fractures may occur possibly leading to complete fracture.
Deformity: Paget’s disease can cause bone to become enlarged and misshapen. For example, if the skull is affected, the enlarged bone is sometimes first noticed when the individual becomes aware that their head is larger and their forehead may be wider than normal. Long-standing disease over many years may cause the weight-bearing bones of the leg to develop a bowing deformity.
"Bone Deformity in Paget’s Disease" an article by Dr D. Hosking can be found in our Member's Area. The photos below show examples of deformity in the arm and the lower leg due to Paget's disease.
Deafness: If the skull is involved, hearing loss can occur.
Fracture: There is an increased risk of fracture, particularly in the long bones of the arm and leg. Fractures may initially be incomplete, (stress fractures or fissure fractures), which are at high risk of complete fracture. Fissure fractures predominantly, but not exclusively, affect weight-bearing bones, such as the thigh bone (femur).
Osteoarthritis: Paget’s disease can predispose to the development of osteoarthritis at adjacent joints. You can read an article by Dr S. Tuck,"Paget's and Osteoarthritis" in our Member's Area.
Neurological complications: Neurological complications can occur, often because of bony overgrowth leading to compression. For example, enlargement of vertebrae in the spine can produce pressure on nerves causing pain, leg weakness or sciatica.
Increased vascularity: Should the bone fracture or surgery be undertaken, active Paget’s disease has the potential to result in excessive blood loss. This is because blood flow increases to areas where Paget’s disease is active.
Heart disease: Paget’s disease does not directly affect the heart but if it is in many bones, is highly active and uncontrolled, the heart may have to work harder to pump extra blood to the affected bones. Whilst heart failure due to this increased blood flow has been reported, it is extremely rare.
Osteosarcoma: An unusual and very rare complication of Paget’s disease is a type of bone cancer, called osteosarcoma. This occurs in less than 1:1,000 people with the disease. Members of the Paget's Association can login to the member area to read an article by experts in Norwich and read about Allan Reid who developed this rare condition. You can also contact our nurse helpline: [email protected] 0161 7994646 or 07713568197. The Bone Cancer Research trust also has information on their website.