Version May 2024
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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 the nearby joints. The condition is slightly more common in men, persons older than 55 or 60 years of age, those with family members affected by Paget disease, and 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, a genetic disease of children, is also distinct from adult Paget disease of bone.
NORMAL BONE GROWTH — To understand Paget disease, it is important to remember that bones are active, living tissues. In addition to being vital for human movement, bones are critical sources of calcium and are birthplaces to the blood cells in our body. Bones are constantly remodeling, cleaning out old bone and replacing it with new. Osteoclasts are the cells that remove bone. Their role is closely linked to osteoblasts, the cells that form new bone to fill in the cavities left by osteoclasts, a process called remodeling. In Paget disease of bone there are larger than normal osteoclasts that are present in greater than normal numbers. Overactivity of the osteoclasts increases the speed of bone remodeling in the pagetic bone, 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 weightbearing 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 buildup 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. (See "Patient education: 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 frequently, but not universally, elevated in people with Paget disease. Alkaline phosphatase is an enzyme that is normally produced by cells in the liver, bone, intestine, and salivary glands. In bone, alkaline phosphatase is made by the bone forming osteoblasts. Alkaline phosphatase produced by bone is increased in Paget disease, which can cause increased blood levels.
Bone scan — A bone scan may be done to identify the bones that may have Paget disease. A bone scan is a test that can detect new areas of bone growth using medication that is injected into a vein; the scan examines bones of the entire body. Bones that are shown to have signs of possible Paget disease can then be x-rayed to confirm the diagnosis.
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 the 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 a bisphosphonate.
Bisphosphonates — Bisphosphonates inhibit the breakdown and removal of bone by inhibiting the osteoclast. The nitrogen-containing bisphosphonates include alendronate, risedronate, pamidronate, and zoledronic acid. The first two are given by mouth, and the last two are given by infusion.
Bisphosphonates 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 infusion into a vein over 15 to 20 minutes. It is the preferred drug for treatment because it is generally well-tolerated and offers patients a prolonged remission of Paget's disease. (See 'Side effects of bisphosphonates' below.)
●Alendronate and risedronate are also effective. These medications are pills taken daily by mouth 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 bisphosphonate that is also effective in many patients with Paget disease. It is given as an infusion 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.
Sometimes other bisphosphonates are used, depending upon cost and availability in individual countries.
Side effects of bisphosphonates — Most people who take bisphosphonates do not have any serious side effects related to the medication. A brief period of fever or flu-like symptoms are the most common side effects of the intravenous forms. Oral alendronate or risedronate may be associated with heartburn or stomach distress, and if this occurs the prescriber of the drug should be notified.
There has been concern about use of the bisphosphonates 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 a bisphosphonate like pamidronate or zoledronic acid. 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 to the bone from the extraction seems to predispose to osteonecrosis of the jaw in rare patients who have received a great deal of previous bisphosphonate.
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 bisphosphonates because of kidney disease or intolerable side effects. Calcitonin 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 reassess therapy.
Other treatments — People with Paget disease may have pain that is related to pagetic activity in the bone or to related complications, including:
●Arthritis of joints near pagetic bone lesions
●A pinched nerve caused by bone overgrowth (eg, sciatica)
●Fractures through the weakened pagetic bone
Pain medications (eg, acetaminophen, ibuprofen, or naproxen) are recommended as needed for treatment of pain that does not improve with the treatment of Paget disease. Consultation with a health care 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 education: Total knee replacement (Beyond the Basics)" and "Patient education: Total hip replacement (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 health care 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 education: 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 education: Primary hyperparathyroidism (Beyond the Basics)
Patient education: Total knee replacement (Beyond the Basics)
Patient education: Total hip replacement (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
Etiology of hypercalcemia
Treatment of Paget disease of bone
The following organizations also provide reliable health information.
●National Library of Medicine
(www.medlineplus.gov/healthtopics.html)
●American Academy of Orthopaedic Surgeons
●American College of Rheumatology
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