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==[[ | ==Overview== | ||
'''Paget's disease''', otherwise known as '''osteitis deformans''', 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 disease<ref name="Paget">Paget J., ''On a form of chronic inflammation of bones (osteitis deformans)'', Trans Med-Chir Soc, 1877,60,37:63</ref>. 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. | |||
== | ==Historical Perspective== | ||
== | ==Classification== | ||
== | ==Pathophysiology== | ||
== | ==Causes== | ||
== | ==Differentiating {{PAGENAME}} 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== | ||
== | ==Screening== | ||
==Natural History, Complications, and Prognosis== | |||
===Natural History=== | |||
===Complications=== | |||
===Prognosis=== | |||
==Diagnosis== | ==Diagnosis== | ||
[[ | ===Diagnostic Criteria=== | ||
===History and Symptoms=== | |||
Many patients do not know they have Paget's disease because they have a mild case with no symptoms. Sometimes, symptoms may be confused with those of arthritis or other disorders. In other cases, the diagnosis is made only after complications have developed. Symptoms can include: | |||
*[[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. | |||
*[[Headache]]s and [[hearing loss]] may occur when Paget's disease affects the skull. | |||
*Pressure on [[nerve]]s may occur when Paget's disease affects the skull or spine. | |||
*[[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 [[scoliosis|curvature of spine]] may occur in advanced cases. | |||
*[[Hip (anatomy)|Hip]] pain may occur when Paget's disease affects the [[pelvis]] or [[femur|thighbone]]. | |||
*Damage to joint [[cartilage]] may lead to [[arthritis]]. | |||
*Teeth may spread intraorally. | |||
*[[Chalkstick fracture]]s. | |||
===Physical Examination=== | |||
Paget's disease may be diagnosed using one or more of the following tests: | |||
*Pagetic bone has a characteristic appearance on [[x-ray]]s. 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 scan]]s 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]] | |||
===Imaging Findings=== | |||
===Other Diagnostic Studies=== | |||
==Treatment== | ==Treatment== | ||
[[ | ===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, 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 [[bisphosphonate]]s 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. | |||
===Surgery=== | |||
Medical therapy prior to surgery helps to decrease bleeding and other complications. Patients who are having surgery should discuss pre-treatment with their physician. 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=== | |||
====Diet and Exercise==== | |||
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]] 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. | |||
[[ | |||
==References== | |||
{{reflist|2}} | |||
[[Category: | [[Category:Endocrinology]] | ||
{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
Revision as of 14:25, 26 July 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
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Overview
Paget's disease, otherwise known as osteitis deformans, 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 disease[1]. 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.
Historical Perspective
Classification
Pathophysiology
Causes
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
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Many patients do not know they have Paget's disease because they have a mild case with no symptoms. Sometimes, symptoms may be confused with those of arthritis or other disorders. In other cases, the diagnosis is made only after complications have developed. Symptoms can include:
- 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 may occur when Paget's disease affects the skull.
- Pressure on nerves may occur when Paget's disease affects the skull or spine.
- 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
Imaging Findings
Other Diagnostic Studies
Treatment
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, 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.
Surgery
Medical therapy prior to surgery helps to decrease bleeding and other complications. Patients who are having surgery should discuss pre-treatment with their physician. 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
Diet and Exercise
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 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.
References
- ↑ Paget J., On a form of chronic inflammation of bones (osteitis deformans), Trans Med-Chir Soc, 1877,60,37:63