PAGET DISEASE OVERVIEW
Paget disease of bone is a disorder of an aging skeleton in which some bones grow abnormally, affecting their size and shape. This can sometimes lead to pain in the bone and in the nearby joints. The condition is slightly more common in men, in persons older than 55 or 60 years of age, in those with family members affected by Paget disease, and in those of European ancestry. Paget disease may affect one bone or many bones and tends to be found in the skull, spine, pelvis, and long bones of the extremity (femur, tibia). A curious aspect of Paget disease is that it does not spread from bone to bone. In a given individual, the bones affected by Paget disease usually remain constant throughout a lifetime. The reason for this is unclear.
There is a type of breast cancer that is referred to as Paget disease of the breast; this is not related to Paget disease of bone and will not be discussed here. Juvenile Paget disease, an autosomal recessive bone disease of children, is not related to this disorder of adult bone either.
NORMAL BONE GROWTH
To understand Paget disease, it is important to remember that bones are active, living tissues vital to human movement, are critical as sources of calcium, and are birthplace to the blood cells in our body. In the work they do, bones constantly remodel, cleaning out old bone and replacing it with new. Osteoclasts are the cells that remove bone. Their role is closely linked to osteoblasts that refill the cavities left by osteoclasts. In Paget disease, the speed with which this remodeling occurs is abnormal, resulting in excessive bone that lacks the strength and shape of normal bone.
PAGET DISEASE CAUSES
The cause of Paget disease is unknown. A person's genes may predispose them to developing Paget disease, while viruses and other environmental exposures may trigger its development.
PAGET DISEASE SYMPTOMS
Most people with Paget disease have no signs or symptoms of bone disease. When there are symptoms, such as pain or deformity, it can be related to Paget disease itself or to complications that occur because of abnormal bone growth.
Pain — Pain may develop directly from a bone affected by the Paget disease or, more often, from complications related to the presence of misshapen bone. Examples of complications include arthritis (when bones near a joint are affected) and numbness or weakness (due to pressure from a bone on a nerve).
Deformities — Abnormal bone growth may cause visible deformities. This is particularly true in affected limbs of the lower extremity or in the skull. If the leg is affected, there can be bowing of the leg, which can cause a limp or can present with back or joint pain due to the abnormal gait. If the skull is involved, the head may slowly enlarge.
Fractures — The abnormal bone of Paget disease is more likely to fracture when exposed to weight-bearing stresses.
Bone tumors — Although rare, the risk of a tumor arising in pagetic bone (both cancerous and noncancerous) is increased in people with Paget disease. This complication occurs in less than 1 percent of people with Paget disease and has been reported most commonly in those with several affected bones.
Calcium and phosphate — The breakdown and build up of bone is essential in regulating the levels of calcium and phosphorus in the blood. In most people with Paget disease, these levels remain normal. However, certain conditions can cause the balance to be disrupted, such as inactivity (eg, after a fracture) or the presence of a second disorder such as hyperparathyroidism (overactive parathyroid glands). (See "Patient information: Primary hyperparathyroidism (Beyond the Basics)".)
Hearing loss — Paget disease will not cause problems at a site distant to the affected bone, so hearing loss in patients with Paget disease is only caused by Paget disease when pagetic bone affects the skull.
PAGET DISEASE DIAGNOSIS
Most people are diagnosed with Paget disease using a combination of a blood tests and radiographic imaging (x-rays or bone scans).
Blood test — A blood test for alkaline phosphatase is usually elevated in people with Paget disease. Alkaline phosphatase is an enzyme that is normally produced in several organs, including the bones, where it is made by osteoblasts.
Bone scan — A bone scan may be done to confirm the diagnosis of Paget disease and/or to identify other bones that are involved. A bone scan is a test that can detect new areas of bone growth using medication that is injected into a vein; the scan may examine bones of the entire body or of a single area.
X-rays — Paget disease may be diagnosed with x-rays. Changes in the bones seen on x-ray may include thickening of the outside of the bone (the cortex) and enlargement or deformity of the bone itself. X-rays are usually done after a bone scan to evaluate potentially affected bones. The information gained from an x-ray is usually sufficient to make the diagnosis of Paget disease.
PAGET DISEASE TREATMENT
Many patients with Paget disease do not have symptoms and do not need treatment. However, treatment may be recommended to decrease the risk of future complications, even if the person has no current symptoms. This may include people who have involvement of the skull, spine, or lower limbs.
Medications — Patients who have pain, bone deformities, or other symptoms related to Paget are usually treated with medications that stop the abnormal bone turnover. The treatment of choice is an aminobisphosphonate.
Bisphosphonates — Aminobisphosphonates inhibit the breakdown and removal of bone by inhibiting the osteoclast. The aminobisphosphonates include alendronate, risedronate, pamidronate, and zoledronic acid. The first two are given by mouth, and the last two are given by infusion. The older bisphosphonates, etidronate and tiludronate, are not aminobisphosphonates and are not usually recommended for people with Paget disease of bone because their potency is less.
Aminobisphosphonates are usually given for a limited period of time, followed by a period of monitoring. (See 'Medication monitoring' below.) These drugs offer the possibility of a long-lasting remission. However, if problems recur, treatment may be repeated. While taking a bisphosphonate, it is important to consume calcium and vitamin D every day in amounts recommended by your clinician. Calcium and vitamin D can be taken as a supplement (table 1); many foods and drinks contain calcium (table 2)
- Zoledronic acid is given as an injection into a vein over 15 to 20 minutes.
- Alendronate and risedronate are taken as a pill for two to six months. These need to be taken first thing in the morning on an empty stomach with a full 8 ounce (approximately 240 mL) glass of plain water (not sparkling). Liquids other than plain water, such as mineral water, coffee, or juice, may interfere with absorption of the medication from the stomach and intestine. After taking alendronate or risedronate, the person must remain upright so the medicine reaches the stomach (sitting or standing, not lying down) and must wait 30 minutes before eating or drinking anything.
- Pamidronate is an older, less potent aminobisphosphonate that is also effective in many patients with Paget disease. It is given into a vein over two to four hours. Reports of resistance to pamidronate and more frequent biochemical relapses in patients with Paget disease have led clinicians to choose zoledronic acid more often than pamidronate when giving an infusion.
Side effects of bisphosphonates — Most people who take bisphosphonates do not have any serious side effects related to the medication. Transient fever or flu-like symptoms are the most common side effects.
There has been concern about use of aminobisphosphonates in people who require invasive dental work. A problem known as avascular necrosis or osteonecrosis of the jaw has rarely developed in people who used these drugs. This is seen more commonly in people with cancer who are given a monthly dose of the aminobisphosphonate. The risk of this problem is much less in people who take bisphosphonates for Paget disease. However, it is sensible to have dental extractions done prior to treatment for Paget disease of bone as trauma seems to predispose to this.
Calcitonin — Synthetic calcitonin is a hormone that is given as an injection under the skin several times a week. Calcitonin may be recommended for people who are unable to tolerate the new aminobisphosphonates because of kidney disease or intolerable side effects. Calcitonin is a safe drug that can ease pain and is partially effective in reducing new bone growth.
Medication monitoring — During and after treatment, blood tests are performed every three to six months to check the level of alkaline phosphatase; a falling level is a good indicator that treatment is working. Other markers of bone turnover may also be recommended by one’s clinician.
When it appears that the medication is effectively reducing new bone formation and the pain has eased, annual visits to one’s clinician may suffice. If the alkaline phosphatase level rises or if symptoms worsen, these are good reasons to re-assess therapy.
Other treatments — People with Paget disease may have pain that is related to Paget as well as pain that is unrelated to the condition. As the skeleton ages, a number of conditions can cause pain in the bones and/or joints, including the following:
- Arthritis of the hip, spine, or knee
- A pinched nerve (eg, sciatica)
- Compression fractures of the spine related to osteoporosis
Pain medications (eg, acetaminophen or ibuprofen) are recommended as needed for treatment of pain that does not improve with the treatment of Paget disease. Consultation with a healthcare provider is recommended to determine which medications and/or other treatments may be most helpful. In some cases, a cane or physical therapy may be recommended.
Surgery — The joints adjacent to affected bones may become stiff and painful due to arthritis. Some patients with severe arthritis pain benefit from surgery to replace the joint. (See "Patient information: Total knee replacement (arthroplasty) (Beyond the Basics)" and "Patient information: Total hip replacement (arthroplasty) (Beyond the Basics)".)
Most people who plan to have surgery are treated for Paget disease of bone for at least two to three months before surgery. This can help to decrease blood flow to the bone, which will help decrease bleeding during surgery.
Outcomes — Most people with Paget disease live long, healthy lives troubled mostly by the musculoskeletal problems imposed by the disease or by other problems of aging.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient information: Paget disease of bone (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Primary hyperparathyroidism (Beyond the Basics)
Patient information: Total knee replacement (arthroplasty) (Beyond the Basics)
Patient information: Total hip replacement (arthroplasty) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clinical manifestations and diagnosis of Paget disease of bone
Diagnosis and classification of osteoarthritis
Etiology of hypercalcemia
Treatment of Paget disease of bone
The following organizations also provide reliable health information.