Paget's Disease of Bone

What Paget's disease of bone is

Bone is constantly renewed. Cells called osteoclasts break down old bone and osteoblasts lay down new bone. In Paget's disease, osteoclasts become larger and overactive in certain areas. Osteoblasts try to keep up, producing a lot of new bone very quickly, but it is laid down in a chaotic mosaic pattern. The result is bone that is thicker and denser on X-ray, yet weaker, more prone to bending and cracking, and with an increased blood supply.

It can affect a single bone (monostotic) or several (polyostotic). It does not usually spread to new bones after diagnosis; it progresses within bones already affected.

The condition is named after Sir James Paget, who described it in 1877. It is unrelated to Paget's disease of the nipple, a form of breast cancer.

Symptoms

About 7 in 10 people have no symptoms. When symptoms occur, they depend on the bones involved:

Other common features:

• deep, aching bone pain, often worse at night
• warmth over an affected bone because of increased blood flow
• arthritis in nearby joints because of changed joint shape
• fractures after minor injuries

Causes and risk factors

The exact cause is unknown. A mix of genetic and environmental factors is involved.

• Age: rare before 40; more common with each decade after 55.
• Family history: up to 1 in 3 people have an affected relative. Variants in the SQSTM1 gene are found in many familial cases. Relatives may be offered an alkaline phosphatase test.
• Ancestry: most common in people of British descent and in regions of British emigration such as Australia, New Zealand and North America; less common in Asia and Africa.
• Possible environmental triggers: a long-standing virus infection (such as measles) inside bone cells has been suggested but not proven.

The disease has become less common and milder in recent decades.

How Paget's disease is diagnosed

1. Alkaline phosphatase (ALP) blood test: raised in most people with active disease. It reflects how fast new bone is being made and is used to monitor treatment. Liver function tests confirm the ALP comes from bone.
2. X-rays: show thickened, enlarged bone, a coarse pattern, and areas of breakdown. They are often diagnostic.
3. Isotope bone scan: shows all affected bones in the body in one scan.
4. Calcium, vitamin D and kidney function before treatment.
5. CT, MRI or biopsy occasionally, if bone cancer or nerve compression is suspected.

Treatment

Not everyone needs drug treatment. The main reason to treat is bone pain caused by active Paget's disease. Treatment may also be given before planned surgery on an affected bone, or when there is high calcium from immobilization.

Bisphosphonates

These medicines slow the overactive osteoclasts.

• Zoledronic acid: a single intravenous infusion over about 15 minutes. It controls disease activity in most people for years, often more than 6 years. It is the preferred treatment.
• Oral bisphosphonates such as risedronate or alendronate, taken daily for a few months, are alternatives when infusion is not suitable.

Before treatment, make sure vitamin D and calcium intake are adequate, as calcium can drop afterward. A dental check is advised because of a rare risk of jaw bone problems. Some people get flu-like symptoms for 1 to 3 days after an infusion.

Pain relief

Acetaminophen (paracetamol) and NSAIDs such as ibuprofen, used at the label dose, help bone and arthritic pain. Pain from arthritis may persist after the Paget's itself is controlled.

Surgery

• joint replacement for severe hip or knee arthritis
• fixing fractures
• osteotomy to straighten a bowed bone
• spinal decompression for nerve compression

Other support

Physical therapy, walking aids, shoe raises for unequal leg length, hearing aids and fall prevention.

Complications

• Fractures, including incomplete "fissure" fractures on the outer curve of bowed bones
• Osteoarthritis in joints next to affected bone
• Hearing loss with skull involvement
• Nerve compression and spinal stenosis
• Hypercalcemia if someone with extensive disease becomes immobile
• Heart strain from increased blood flow in very extensive disease (rare)
• Osteosarcoma: a bone cancer arising in Pagetic bone, in fewer than 1 in 100 people

Outlook

Paget's disease is not usually life-threatening, and most people live normal lives. Treatment relieves pain in many people, but cannot reverse deformity, deafness or arthritis that have already developed. Long-term follow-up typically includes periodic ALP tests and asking about pain, with retreatment if symptoms return with evidence of activity.

Frequently asked questions

What are the first signs of Paget's disease of bone?

Often there are none, and it is found on a blood test or X-ray done for another reason. When symptoms appear, the most common is a deep, persistent ache in a bone such as the pelvis, spine or thigh, sometimes with warmth over it or a gradually bowing leg.

Is Paget's disease of bone serious?

For most people, it is a manageable condition that does not shorten life. Problems come from complications such as arthritis, fractures, deformity, hearing loss or nerve compression. Bone cancer is a rare but serious complication, so new severe pain or swelling needs prompt review.

What is the best treatment for Paget's disease of bone?

A single intravenous infusion of zoledronic acid is the most effective treatment for bone pain from active disease and often keeps it controlled for many years. Oral bisphosphonates are an alternative. Pain relievers, physical therapy and surgery treat complications.

Is Paget's disease hereditary?

It can be. Around 15 to 30% of people have an affected relative, and variants in the SQSTM1 gene are common in families with the condition. Having the gene does not guarantee you will develop it. Relatives may be offered blood tests if they have symptoms.

Can Paget's disease of bone be cured?

There is no cure, but treatment can switch off disease activity and relieve pain for years. It cannot reverse bone deformity, enlarged bones or hearing loss that have already happened, which is why early treatment of symptomatic disease is worthwhile.