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__NOTOC__
{{Infobox_Disease |
  Name          = {{PAGENAME}} |
  Image          = Paget's Disease-x-ray.jpeg |
  Caption        = X-ray of Paget's disease |
  DiseasesDB    = 9479 |
  ICD10          = {{ICD10|M|88||m|86}} |
  ICD9          = {{ICD9|731.0}} |
  ICDO          = |
  OMIM          = 602080 |
  MedlinePlus    = 000414 |
  MeshID        = D010001 |
}}
{{SI}}
{{SI}}
{{CMG}}
{{CMG}}
'''Associate Editor-In-Chief:''' {{CZ}}


==Overview==
==Overview==
The term '''overweight''' is generally used to indicate that a [[human]] has more [[body fat]] than is considered useful for the optimal functioning of the body.  Being overweight is a fairly common condition for many people, especially those in developed nations where food supplies are plentiful and lifestyles often do not involve a lot of activities that generate caloric expenditure. Recent studies have indicated that as much as 64% of the adult US population is overweight, and this number is increasing.<ref>{{cite journal | author=Katherine M. Flegal, PhD; Margaret D. Carroll, MS; Cynthia L. Ogden, PhD; Clifford L. Johnson, MSPH | title=Prevalence and Trends in Obesity Among US Adults, 1999-2000 | journal=[[Journal of the American Medical Association|JAMA]] | year=2002 | volume=288 | issue=14 | pages=1723&ndash;1727 | url=http://jama.ama-assn.org/cgi/content/full/288/14/1723  | id=PMID 12365955}}.</ref> A series of graphics from the CDC also describes the obesity prevalence trends in the U.S. in the past 2 decades: [http://www.epidemiologic.org/2006/10/obesity-epidemic-us-temporal-trends.html Obesity Epidemic: U.S. Temporal Trends 1985-2004]


A healthy body requires a minimum amount of fat for the proper functioning of the hormonal, reproductive, and immune systems, as [[thermal insulation]], as [[shock absorber|shock absorption]] for sensitive areas, and as excess energy for future use. But the accumulation of too much storage fat can impair movement and flexibility, and can alter the appearance of the body.
'''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.
== Classification ==
 
The degree to which a person is overweight is generally described using an indication of the amount of excess body fat present.  There are several common ways to measure the amount of fat present in an individual's body.(See also [[body fat percentage]]):
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.
* '''[[weighing scale|Simple Weighing]]:''' The weight of the individual is measured and compared to an estimated ideal weight. This is the easiest and most common method, but by far the least accurate, as it only measures one quantity (weight) and often does not take into account many factors such as height, body type, and relative amount of muscle mass.
 
* '''[[Body Mass Index]] (BMI):'''  This is an adaptation of simple weighing which attempts to take into account the subject's general body size by dividing the weight by the height squared (the units for BMI are kg/m<sup>2</sup>, but are rarely referenced, and BMI numbers are typically written and used as unitless numbers). This provides a slightly more accurate representation than simply measuring raw weight, but still ignores many factors which can affect the results, and is generally not accurate for many individuals.
== Risk Factors ==
* '''Skinfold [[Calipers]] or "pinch test":'''  With this method, the skin at several specific points on the body is pinched and the thickness of the resulting fold is measured. This measures the thickness of the layers of fat located under the skin, from which a general measurement of total amount of fat in the body is calculated. This method can be reasonably accurate for many people, but it does assume particular patterns for fat distribution over the body which may not apply to all individuals, and does not account for fat deposits which may not be directly under the skin. Also, as the measurement and analysis generally involves a high degree of practice and interpretation, for an accurate result it must be performed by a professional and cannot generally be done by patients themselves.
*Not known
* '''[[Bioelectrical impedance analysis]]:'''  This method involves passing a small electrical current through the body and measuring the body's resistance to the electrical flow. As fat and muscle conduct electricity differently, this method can provide a direct measurement of the percentage of body fat present as compared to muscle mass. In the past, this technique could only be performed reliably by trained professionals with specialized equipment, but it is now possible to buy "home kits" which allow individuals to do this themselves with a minimum of training. Despite the improved simplicity of this process over the years, however, there are a number of factors which can affect the results, including hydration and body temperature, so a fair amount of care must still be taken when applying this test to ensure that the results are in fact accurate and applicable.
 
* '''[[hydrostatic equilibrium|Hydrostatic]] Weighing:''' Considered one of the more accurate methods of measuring body fat, this technique involves completely submerging the subject underwater and using special equipment to measure his or her weight while submerged. This weight is then compared with "dry weight" as recorded outside the water to determine overall body density.  As fat is less dense than muscle, careful application of this technique can provide a reasonably close estimate of fat content in the body.  This technique does, however, require expensive specialized equipment and trained professionals to administer it properly.
== Epidemiology and Demographics ==
* '''[[DEXA]] (dual energy X-ray absorptiometry):'''  Originally developed to measure bone density, DEXA imaging has also come to be used as a precise way to determine body fat content by using the density of various body tissues to identify which portions of the body are fat. This test is generally considered to be very accurate, but requires a great deal of expensive medical equipment and trained professionals to perform.
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
 
== Pathophysiology & Etiology==
* The cause of Paget's Disease is unknown
* The early phase of the disease is termed the destructive phase of disease
* The next phase, commonly termed the mixed phase, involves the formation of new pagetic bone.   
In the next phase, called the ''scelrotic'' phase, the resorptive rate declines relative to the rate of bone formation leading to the development of less vascular bone and a positive calcium balance.
 
==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.
 
==Diagnosis==
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]]
 
== Differential Diagnosis ==
Since many patients are asymptomatic, the disorder is commonly discovered by radiologic examination for an unrelated disease or because of an elevated plasma [[alkaline phosphatase]].
 
==Prognosis==
The outlook is generally good, particularly if treatment is given before major changes in the affected bones have occurred. Any bone or bones can be affected, but Paget's disease occurs most frequently in the spine, skull, pelvis, thighs, and lower legs. In general, symptoms progress slowly, and the disease does not spread to normal bones. Treatment can control Paget's disease and lessen symptoms but is not a cure. Osteogenic sarcoma, a form of bone [[cancer]], is an extremely rare complication that occurs in less than one percent of all patients.
 
==Other medical conditions==
Paget's disease may lead to other medical conditions, including:
*[[Arthritis]]: Long bones in the leg may bow, distorting alignment and increasing pressure on nearby joints. In addition, Pagetic bone may enlarge, causing joint surfaces to undergo excessive wear and tear. In these cases, pain may be due to a combination of Paget's disease and osteoarthritis.
*[[Deafness|Loss of hearing]] in one or both ears may occur when Paget's disease affects the skull and the bone that surrounds the inner ear. Treating the Paget's disease may slow or stop hearing loss. [[Hearing aid]]s may also help. It is believed by some that the disease was responsible for Beethoven's deafness.
*[[Cardiovascular disease]]: In severe Paget's disease (i.e. with more than 15% skeletal involvement), the heart works harder to pump blood to affected bones. Left ventricular hypertrophy is an associated finding. High-output congestive failure may rarely occur. Similarly, calcification of the aortic valve and associated vessels may occur due to turbulent flow caused by increased cardiac output.
*[[Kidney stone]]s are somewhat more common in patients with Paget's disease.
*[[Nervous system]]: Pagetic bone can cause pressure on the brain, [[spinal cord]], or nerves, and reduced blood flow to the brain and spinal cord.
*[[Sarcoma]]: Rarely, Paget's disease is associated with the development of a malignant tumor of bone. When there is a sudden onset or worsening of pain, sarcoma should be considered.
*When Paget's disease affects the facial bones, the [[teeth]] may become loose. Disturbance in chewing may occur.
*Rarely, when the skull is involved, the nerves to the [[eye]] may be affected, causing some [[Visual loss|loss of vision]].
 
Paget's disease is not associated with [[osteoporosis]]. Although Paget's disease and osteoporosis can occur in the same patient, they are different disorders. Despite their marked differences, several treatments for Paget's disease are also used to treat osteoporosis.
 
==Treatment==
===Types of physicians===
The following types of medical specialists are generally knowledgeable about treating Paget's disease.
 
*[[Endocrinologist]]s -- Internists who specialize in hormonal and metabolic disorders.
*Rheumatologists -- Internists who specialize in joint and muscle disorders.
*Specialists -- Orthopedic surgeons, [[neurologist]]s, and otolaryngologists (physicians who specialize in ear, nose, and throat disorders) may be called upon to evaluate specialized symptoms.
 
===Drug 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.  
 
====Bisphosphonates====
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).


Despite the inherent inaccuracies, the most common method for discussing this subject used by researchers and advisory institutions is [[body mass index]] (BMI) numbers.  Definitions of what is considered to be overweight change from time to time and sometimes from country to country, but the current definition proposed by both the US [[National Institutes of Health]] and the [[World Health Organization]] designates anyone with a BMI of 25 kg/m<sup>2</sup> or more to be overweight.
====[[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.


BMI, however, does not account for differing amounts of [[muscle]] mass, [[genetics|genetic]] factors, or many other individual variations, and thus many individuals can have BMIs less than 25 and still be considered overweight, while others may have BMIs significantly higher without falling into this category<ref>{{cite journal | author=Dympna Gallagher, Steven B Heymsfield, Moonseong Heo, Susan A Jebb, Peter R Murgatroyd and Yoichi Sakamoto | title= Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index | journal=[[AJCN]] | year=2000 | volume=72 | issue=3 | pages=694&ndash;701 | url=http://www.ajcn.org/cgi/content/full/72/3/694  | id=PMID 10966886}}.</ref>.  Many of the more accurate methods mentioned above for determining body fat content can provide better indications of whether a particular individual is overweight or not.
===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.


If an individual is sufficiently overweight that excess body fat could present substantial [[health]] risks, he or she is considered to be [[obese]]. It is possible for someone to be overweight without being obese (according to the NIH and WHO, a BMI between 25 and 30 is considered to be "overweight" but not "obese").  Again, the designation
*Fractures -- Surgery may allow fractures to heal in better position.
of "obesity" is subject to a great deal of interpretation and many individual factors, so an individual with a BMI well below 30 may be considered to be obese depending on their particular condition, while in some cases a BMI above 30 may not actually indicate obesity (although likely still does indicate being overweight).
*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.
== Causes ==
*Bone deformity -- Cutting and realignment of Pagetic bone (osteotomy) may help painful weight-bearing joints, especially the knees.


Being overweight is generally caused by the intake of more calories (by eating) than are expended by the body (by exercise and everyday living). Factors which may contribute to this imbalance include:
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.


* Limited exercise and sedentary lifestyle
===Diet and Exercise===
* [[Overeating]]
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.
* Poor nutrition
* [[genetics|Genetic]] predisposition
* Hormone imbalances (e.g. [[hypothyroidism]])
* Metabolic disorders, which could be caused by repeated attempts to lose weight by [[Yo-yo dieting|Weight cycling]],
* An [[eating disorder]] (such as [[binge eating disorder]])
* [[Alcoholism]]
* [[Stress (medicine)|Stress]]
* Insufficient [[sleep]]
* Psychotropic medications
* [[Smoking cessation]] and other [[stimulant]] withdrawal


The amount of body fat is regulated to some extent subconsciously by the brain (by controlling caloric intake through appetite and food preferences).  Although the exact mechanisms by which this occurs are not entirely known, one common theory suggests that each person may possess an inherent "set point" weight which the brain attempts to maintain, and that this set point may vary for each individual depending on a variety of factors including genetic predisposition, environment, and past experience.
[[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.


This leads to the conclusion that some individuals may be predisposed to naturally maintaining different body weights than others, and thus it may be easier for some people to avoid being overweight, while others may find it much more difficult.  It also suggests, however, that an individual's set point may be changeable with appropriate environment and conditioning.
==Microscopical Findings of Paget disease==
== Health-related Implications ==
While the health issues associated with [[obesity]] are well accepted within the medical community, the health implications of the overweight category are more controversial. The generally accepted view has been that overweight often shares adverse risks with obesity, relative to normal weight. Adams et al. estimated that risk of death increases by 20 to 40 percent among overweight persons.<ref>{{cite journal | author=Kenneth F. Adams, Ph.D., Arthur Schatzkin, M.D., Tamara B. Harris, M.D., Victor Kipnis, Ph.D., Traci Mouw, M.P.H., Rachel Ballard-Barbash, M.D., Albert Hollenbeck, Ph.D., and Michael F. Leitzmann, M.D. | title=Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old | journal=[[NEJM]] |year=2006 | volume=355 | issue=8 | pages=763&ndash;788 | url=http://content.nejm.org/cgi/content/short/355/8/763?query=prevarrow}}</ref>


Flegal et al., however, found that mortality rates for individuals who are classified as overweight (BMI 25 to 30) may actually be lower than for those with an "ideal" weight (BMI 18.5 to 25)<ref>{{cite journal | author=Katherine M. Flegal, PhD; Barry I. Graubard, PhD; David F. Williamson, PhD; Mitchell H. Gail, MD, PhD | title=Excess Deaths Associated With Underweight, Overweight, and Obesity | journal=[[Journal of the American Medical Association|JAMA]] | year=2005 | volume=293 | issue=15 | pages=1861&ndash;1867 | url=http://jama.ama-assn.org/cgi/content/abstract/293/15/1861 |id=PMID 15840860}}.</ref>. 
{{#ev:youtube|dC2TrqcEJEA}}


Psychological well-being is also at risk in the overweight individual.  Discrimination against fat persons is common socially and legally.  This may affect their ability to find a mate or employment. The receipt of overt remarks from childhood into old age also shape the personality of the overweight individual, either making him/her more resolute and obstinate or too willing to please others.
==References==
{{Reflist|2}}


== Treatment ==
==See Also==
===Medical Therapy===
A large number of people undergo some form of treatment to attempt to reduce their weight, usually either in an attempt to improve their health, to improve their lifestyle, or for cosmetic reasons.  The generally recommended treatment for being overweight is a [[dieting|modified or controlled diet]] in conjunction with increased [[exercise]]. For those who are obese rather than overweight, more intensive therapies such as drugs or surgery are sometimes used (see [[Obesity]]).


Studies suggest that reducing calorie intake by itself (dieting) may have short-term effects but does not lead to long-term weight loss, and can often result in gaining back all of the lost weight and more in the longer term. For this reason, it is generally recommended that weight-loss diets not be attempted on their own but instead in combination with increased exercise and long-term planning and weight management.
* [[Paget's disease of the breast]]
* [[Paget-Schroetter disease]]
* [[Extramammary Paget's disease]] (EMPD)


The health benefits of weight loss are also somewhat unclear.  While it is generally accepted that for significantly obese patients, losing weight can reduce health risks and improve quality of life, there is some evidence to suggest that for merely overweight patients, the health effects of attempting to lose weight may actually be more detrimental than simply remaining overweight<ref>{{cite journal | author=Sørensen TI, Rissanen A, Korkeila M, Kaprio J. | title=Intention to Lose Weight, Weight Changes, and 18-y Mortality in Overweight Individuals without Co-Morbidities. | journal=[[PLoS]] | year=2005 | volume=2 | issue=6 | pages=e171 | url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020171  | id=PMID 15971946}}.</ref>.  Moreover, for all individuals, repeatedly losing weight and then gaining it back ("[[yo-yo dieting]]"), is believed to do more harm than good and can be the cause of significant additional health problems.  This is caused by the loss of more muscle than fat.
{{Diseases of the musculoskeletal system and connective tissue}}


There is no healthy, short-term solution for solving obesity, or being overweight.  Changes in lifestyle, such as more exercise or dieting, must be permanent changes.


== References ==
[[Category:Skeletal disorders]]
{{reflist|2}}
[[Category:Orthopedics]]
[[Category:Needs patient information]]


[[de:Osteodystrophia deformans]]
[[es:Osteítis deformante]]
[[fr:Maladie de Paget]]
[[nl:Ziekte van Paget]]
[[pl:Choroba Pageta]]
[[pt:Doença de Paget]]
[[fi:Pagetin tauti]]


[[Category:Health risks]]
[[Category:Nutrition]]
[[Category:body shape]]
[[Category:primary care]]


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Revision as of 12:02, 3 June 2016

Sandbox/01
X-ray of Paget's disease
ICD-10 M88
ICD-9 731.0
OMIM 602080
DiseasesDB 9479
MedlinePlus 000414
MeSH D010001

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]


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.

Risk Factors

  • Not known

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

Pathophysiology & Etiology

  • The cause of Paget's Disease is unknown
  • The early phase of the disease is termed the destructive phase of disease
  • The next phase, commonly termed the mixed phase, involves the formation of new pagetic bone.

In the next phase, called the scelrotic phase, the resorptive rate declines relative to the rate of bone formation leading to the development of less vascular bone and a positive calcium balance.

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:

Diagnosis

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

Differential Diagnosis

Since many patients are asymptomatic, the disorder is commonly discovered by radiologic examination for an unrelated disease or because of an elevated plasma alkaline phosphatase.

Prognosis

The outlook is generally good, particularly if treatment is given before major changes in the affected bones have occurred. Any bone or bones can be affected, but Paget's disease occurs most frequently in the spine, skull, pelvis, thighs, and lower legs. In general, symptoms progress slowly, and the disease does not spread to normal bones. Treatment can control Paget's disease and lessen symptoms but is not a cure. Osteogenic sarcoma, a form of bone cancer, is an extremely rare complication that occurs in less than one percent of all patients.

Other medical conditions

Paget's disease may lead to other medical conditions, including:

  • Arthritis: Long bones in the leg may bow, distorting alignment and increasing pressure on nearby joints. In addition, Pagetic bone may enlarge, causing joint surfaces to undergo excessive wear and tear. In these cases, pain may be due to a combination of Paget's disease and osteoarthritis.
  • Loss of hearing in one or both ears may occur when Paget's disease affects the skull and the bone that surrounds the inner ear. Treating the Paget's disease may slow or stop hearing loss. Hearing aids may also help. It is believed by some that the disease was responsible for Beethoven's deafness.
  • Cardiovascular disease: In severe Paget's disease (i.e. with more than 15% skeletal involvement), the heart works harder to pump blood to affected bones. Left ventricular hypertrophy is an associated finding. High-output congestive failure may rarely occur. Similarly, calcification of the aortic valve and associated vessels may occur due to turbulent flow caused by increased cardiac output.
  • Kidney stones are somewhat more common in patients with Paget's disease.
  • Nervous system: Pagetic bone can cause pressure on the brain, spinal cord, or nerves, and reduced blood flow to the brain and spinal cord.
  • Sarcoma: Rarely, Paget's disease is associated with the development of a malignant tumor of bone. When there is a sudden onset or worsening of pain, sarcoma should be considered.
  • When Paget's disease affects the facial bones, the teeth may become loose. Disturbance in chewing may occur.
  • Rarely, when the skull is involved, the nerves to the eye may be affected, causing some loss of vision.

Paget's disease is not associated with osteoporosis. Although Paget's disease and osteoporosis can occur in the same patient, they are different disorders. Despite their marked differences, several treatments for Paget's disease are also used to treat osteoporosis.

Treatment

Types of physicians

The following types of medical specialists are generally knowledgeable about treating Paget's disease.

  • Endocrinologists -- Internists who specialize in hormonal and metabolic disorders.
  • Rheumatologists -- Internists who specialize in joint and muscle disorders.
  • Specialists -- Orthopedic surgeons, neurologists, and otolaryngologists (physicians who specialize in ear, nose, and throat disorders) may be called upon to evaluate specialized symptoms.

Drug 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.

Bisphosphonates

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.

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.

Microscopical Findings of Paget disease

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References

  1. ↑ Paget J., On a form of chronic inflammation of bones (osteitis deformans), Trans Med-Chir Soc, 1877,60,37:63

See Also

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