Paget's disease of bone
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammadmain Rezazadehsaatlou [2];
Synonyms and Keywords: Commonly known as Paget's disease; Historically known as osteitis deformans
Overview
Paget's disease, otherwise known as osteitis deformans, is the second most common bone disease after osteoporosis worldwide. It is characterized by focal regions of highly exaggerated bone remodeling, with different abnormalities in all phases of the bone remodeling process. Paget's diseases of bone is a chronic disorder that typically results in enlarged and deformed bones. It is named after Sir James Paget, the British surgeon who first described this problem. The excessive breakdown and formation of bone tissue that occurs with Paget's disease can cause bone to weaken, resulting in bone pain, arthritis, deformities, and fractures. Paget's disease may be caused by a slow virus infection (i.e., paramyxoviruses such as measles and respiratory syncytial virus), present for many years before symptoms appear. There is also a hereditary factor since the disease may appear in more than one family member. Paget's disease is rarely diagnosed in people less than 40 years of age. Men are more commonly affected than women. Prevalence of Paget's disease ranges from 1.5 to 8 percent depending on age and country of residence. Prevalence of familial Paget's disease (where more than one family member has the disease) ranges from 10 to 40 percent in different parts of the world. Because early diagnosis and treatment is important, after age 40, siblings and children of someone with Paget's disease may wish to have an alkaline phosphatase blood test every 2 or 3 years. If the alkaline phosphatase level is above normal, other tests such as a bone-specific alkaline phosphatase test, bone scan, or x-ray can be performed.
Paget's disease of bone affects the normal body's bone recycling process, in which new bone tissue gradually replaces old bone tissue. Accordingly, the disease made bone fragile and misshapen. Paget's disease of bone can affect any bone in human body. It appears most often in the spine, pelvis, long bones of the limbs, and skull. It can be present in just one bone or in several bones. It can affect the entire bone or just part of it.
The risk of Paget's disease of bone increases with age. Paget's disease of bone most commonly affects the pelvis, skull, spine and legs. Complications of Paget's disease of bone are broken bones, hearing loss and pinched nerves in spine. Bisphosphonates — the medications also used to strengthen bones weakened by osteoporosis — are the mainstay of treatment. For patients who have complications, surgery may be necessary
Historical Perspective
Classification
Pathophysiology
Causes
The main cause /causes of Paget's disease of bone is not well known yet. But its thought that a combination of environmental and genetic factors contribute to this disease. Several genes appear to be linked to the occurrence of the disease. Also it might be related to a viral infection in bone cells, but this theory is controversial.
In normal bone, a normal process called remodeling. Bone is absorbed and then reformed in response to the normal stresses on the skeleton.
- osteoclasts: cells that absorb bone.
- osteoblasts: cells that make new bone.
In Paget's disease, osteoclasts are more active than osteoblasts. This means that there is more bone absorption than normal. The osteoblasts try to keep up by making new bone, but they overreact and make excess bone that is abnormally large and deformed.Since in normal bone there is a tight overlapping structure, like a well-constructed brick wall. Bone involved with the Paget's disease has an irregular mosaic pattern, as though the bricks were just dumped in place consequently the bones are large and dense, but weak and brittle. The bone is prone to fractures, bowing, and deformities.
Differentiating Paget's disease of bone from Other Diseases
Epidemiology and Demographics
The incidence of
- Likelihood of occurrence increases with age
- Radiologic surveys show the frequency in adults is less than 1% in the US, Great Britain, and Australia
- The disease is rare in India, Japan, Scandanavia, and the Middle East
Risk Factors
Risk factors of Paget's disease of bone include:
- Age. People older than 40 are most likely to develop Paget's disease of bone.
- Sex. Men are more commonly affected than are women.
- National origin. Paget's disease of bone is more common in England, Scotland, central Europe and Greece. It's uncommon in Scandinavia and Asia.
- Family history. Having a relative with Paget's disease of bone more likely develop the risk of Paget's disease of bone.
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
In most patients the Paget's disease of bone progresses slowly. The point is this disease can be managed effectively in nearly all people. Possible complications of Paget's disease of bone include:
- Fractures and deformities. Affected bones break more easily. Extra blood vessels in these deformed bones cause them to bleed more during surgeries. Leg bones can bow, which can affect ability to walk.
- Osteoarthritis. Misshapen bones can increase the amount of stress on nearby joints, which can cause osteoarthritis.
- Neurologic problems. When Paget's disease of bone occurs in an area where nerves pass through the bone, such as the spine and skull, the overgrowth of bone can compress and damage the nerve, causing pain, weakness or tingling in an arm or leg or hearing loss.
- Heart failure. Extensive Paget's disease of bone may force heart to work harder to pump blood to the affected areas of body. Sometimes, this increased workload can lead to heart failure.
- Bone cancer. Bone cancer occurs in about 1 percent of people with Paget's disease of bone..
Prognosis
Diagnosis
Lab tests
People who have Paget's disease of bone usually have elevated levels of alkaline phosphatase in their blood, which can be revealed by a blood test.
Diagnostic Criteria
History and Symptoms
Many patients do not know they have Paget's disease of bone because they have a mild case with no symptoms. When symptoms occur, the most common complaint is bone pain.Sometimes, symptoms may be confused with those of arthritis or other disorders. Due to the nature of this disease which causes the generation of new bone faster than normal, the rapid remodeling produces leads to softer and weaker bone; accordingly this process cause the bone pain, deformities and fractures.
Meanwhile the symptoms of the Paget's disease of bone are:
- Bone pain is the most common symptom. Bone pain can occur in any bone affected by Paget's disease. It often localizes to areas adjacent to the joints.
- Headaches and hearing loss due to the overgrowth of bone when Paget's disease affects the skull.
- Pressure on nerves may occur when Paget's disease affects the skull or spine consequently there might be pain, tingling and numbness in an arm or leg.
- Somnolence (drowsiness) due to vascular steal syndrome of the skull.
- Paralysis due to vascular steal syndrome of the vertebrae.
- Increased head size, bowing of limb, or curvature of spine may occur in advanced cases.
- Hip pain may occur when Paget's disease affects the pelvis or thighbone.
- Damage to joint cartilage may lead to arthritis.
- Teeth may spread intraorally.
- Chalkstick fractures.
Physical Examination
Paget's disease may be diagnosed using one or more of the following tests:
- Pagetic bone has a characteristic appearance on x-rays. A skeletal survey is therefore indicated.
- An elevated level of alkaline phosphatase in the blood in combination with normal calcium, phosphate, and aminotransferase levels in an elderly patient are suggestive of Paget's disease.
- Urinary Hydroxyproline has been elevated in many patients and it is a marker used traditionally.
- Bone scans are useful in determining the extent and activity of the condition. If a bone scan suggests Paget's disease, the affected bone(s) should be x-rayed to confirm the diagnosis.
Laboratory Findings
Electrolyte and Biomarker Studies
There is an elevation of the alkaline phosphatase in patients blood, which can be revealed by a blood test.
Imaging Findings
Bone changes due to the Paget's disease of bone can be investigated using:
- X-rays.
- The first indication of Paget's disease of bone is often abnormalities found on X-rays done for other purposes. Meanwhile, the X-ray imaging can show reabsorption of bone, enlargement of the bone and deformities that are characteristic of Paget's disease of bone, such as bowing of the long bones.
- Bone scan.
- In a bone scan, radioactive material is injected into body and this material travels to the spots on your bones most affected by Paget's disease of bone, so they light up on the scan images.
Other Diagnostic Studies
Treatment
If the disease is active (According to the elevated alkaline phosphatase level and other indicative founding) and affecting important and high-risk sites in body, such as skull or spine then the treatment are necessary to prevent complications, even if you don't have symptoms. The goal of treatment is to relieve bone pain and prevent the progression of the disease. The U.S. Food and Drug Administration has approved the following treatments for Paget's disease:
Medications
Osteoporosis drugs (bisphosphonates) are the most common treatment for Paget's disease of bone. Oral bisphosphonates are generally well-tolerated, but they may irritate your gastrointestinal tract. :
Medical Therapy
The goal of treatment is to relieve bone pain and prevent the progression of the disease. The U.S. Food and Drug Administration has approved the following treatments for Paget's disease:
Chronic Pharmacotherapies
Cytotoxic drugs like plicamycin and dactinomycin are no longer used for therapy
- Bisphosphonates are used to inhibit bone resorption
- Etidronate has been used at 20 mg/kg body weight per day and is effective in producing clinical improvement
- osteomalacia is a potential complication of therapy
- Alendronate (Fosamax), pamidronate, risendronate, and tiludronate are the bisphosphonates most commonly used now as they are more potent than etidronate and do not result in the same mineralization defects
- Alendronate is approx. 700-fold more potent than etidronate
- Alendronate (oral administration) and pamidronate (intravenous administration) are approved for use in the US
Common bisphosphonates and their use:
- Alendronate is administered orally with water 30-60 minutes before breakfast after an overnight fast
- Dose is 40 mg/d for 6 months
- Pamidronate is given intravenously
- Dose is 30 mg/d in 5% glucose in water or normal saline over 4h ion 3 successive days
- Calcitonin will be replaced by bisphosphonates for primary treatment of severe disease, but calcitonin can still be used for patients who cannot tolerate alendronate due to gastrointestinal side effects
- The administration of calcitonins suppresses the pagetic lesion which leads to a decrease in bone pain.
- Calcitonin also improves neurologic symptoms and decreases elevated cardiac output
- Some individuals do not respond to porcine or salmon calcitonins
- Calcitonin can be administered by nasal spray at doses of 200 IU/d.
Bisphosphonate
Five bisphosphonates are currently available. In general, the most commonly prescribed are the three most potent bisphosphonates: Actonel®, Fosamax® and Aredia®. Didronel® and Skelid® may be appropriate therapies for selected patients but are less commonly used. As a rule, bisphosphonate tablets should be taken with 6-8 oz of tap water on an empty stomach. None of these drugs should be used by people with severe kidney disease.
- Didronel® (etidronate disodium) -- Tablet; approved regimen is 200-400 mg once daily for 6 months; the higher dose (400 mg) is more commonly used; no food, beverages, or medications for 2 hours before and after taking; course should not exceed 6 months, but repeat courses can be given after rest periods, preferably of 3-6 months duration.
- Aredia® (pamidronate disodium) -- Intravenous; approved regimen 30 mg infusion over 4 hours on 3 consecutive days; more commonly used regimen 60 mg over 2-4 hours for 2 or more consecutive or non-consecutive days.
- Fosamax® (alendronate sodium) -- Tablet; 40 mg once daily for 6 months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
- Skelid® (tiludronate disodium) -- Tablet; 400 mg (two 200 mg tablets) once daily for 3 months; may be taken any time of day, as long as there is a period of 2 hours before and after resuming food, beverages, and medications.
- Actonel® (risedronate sodium) -- Tablet; 30 mg once daily for 2 months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
Calcitonin
- Miacalcin® is administered by injection; 50 to 100 units daily or 3 times per week for 6-18 months. Repeat courses can be given after brief rest periods. Miacalcin may be appropriate for certain patients but is seldom used. The nasal spray form of this drug is not approved for the treatment of Paget's disease.
Rarely, bisphosphonate therapy has been linked to severe muscle, joint or bone pain, which might not resolve when the medication is discontinued. Bisphosphonates can also increase the risk of a rare condition in which a section of jawbone dies and deteriorates (osteonecrosis of the jawbone), usually associated with active dental disease or oral surgery.
If patinets can't tolerate bisphosphonates, the n the calcitonin (Miacalcin), a naturally occurring hormone involved in calcium regulation and bone metabolism should be considered in this regard. Side effects may include nausea, facial flushing and irritation at the injection site.
Surgery
- Surgical intervention might be required to:
- Help fractures heal
- Replace joints damaged by severe arthritis
- Realign deformed bones
- Reduce pressure on nerves
Paget's disease of bone causes the body to produce too many blood vessels in the affected bones, increasing the risk of serious blood loss during an operation. Medical therapy prior to surgery helps to decrease bleeding and other complications. There are generally three major complications of Paget's disease for which surgery may be recommended.
- Fractures -- Surgery may allow fractures to heal in better position.
- Severe degenerative arthritis -- If disability is severe and medication and physical therapy are no longer helpful, joint replacement of the hips and knees may be considered.
- Bone deformity -- Cutting and realignment of Pagetic bone (osteotomy) may help painful weight-bearing joints, especially the knees.
Complications resulting from enlargement of the skull or spine may injure the nervous system. However, most neurologic symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery.
Prevention
To reduce your risk of complications associated with Paget's disease of bone, the following mentioned factor can be helpful:
- Prevent falls
- Diet
In general, patients with Paget's disease should receive 1000-1500 mg of calcium, adequate sunlight, and at least 400 units of vitamin D daily. This is especially important in patients being treated with bisphosphonates. Patients with a history of kidney stones should discuss calcium and vitamin D intake with their physician.
- Exercise regularly. Exercise is very important in maintaining skeletal health, avoiding weight gain, and maintaining joint mobility. Since undue stress on affected bones should be avoided, patients should discuss any exercise program with their physician before beginning.Regular exercise is essential for maintaining joint mobility and bone strength. Some activities may place too much stress on the affected bones.