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Paget Disease of the Bone
Paget Disease

Osteitis deformans, also known as Paget's disease, is a condition frequently observed in elderly patients, despite the fact that it's prevalence has decreased over the last 20 years. With unclear etiology, this pathological entity is characterized by abnormal behavior of osteoclasts and osteoblasts, leading to pathological bone formation. The disease may involve one or more sites and may progress to fractures, osteosarcoma and cardiovascular abnormalities.

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Presentation

This disease has an ongoing character, may involve one or more bones at first, but secondary dissemination does not occur.

Patients may be asymptomatic or may have complaints such as bone pain, that is dull, quasi-permanent and accentuated during the night and with weight burden. Uninvolved areas may also hurt, because of the redistribution of the mechanical forces.

Involved bones may present with deformities like bowing. With skull implication, symptoms like headaches, hearing loss, vertigo, tinnitus, changes in vision and cranial nerve palsies occur. If the cranium descends onto the cervical spine, patients experience paresthesias and bowel or bladder incontinence. Other cranial complications include hydrocephalus and subsequent brain compression symptoms: syncope, nausea, ataxia, dementia.

Facial bones may also undergo changes, leading to occlusion abnormalities and loss of teeth.

As axial bones are more frequently affected, patients usually describe lower back, cervical or hip pain. Fractures and arthritis are not uncommon, but if the pain is constantly increasing and the surrounding tissues become swollen, a radiography should be performed in order to exclude osteosarcoma.

Osteitis deformans is characterized by increased vascularization of the affected areas. This can lead to high-output heart failure in patients with decreased contractility reserve [1]. Arteriosclerosis and mitral and aortic valve calcifications have been shown to be related to disease progression and further worsen cardiovascular status [2] [3] [4].

Entire Body System

  • Pain

    If they do occur, symptoms may include: Bone pain, joint pain or stiffness, and neck pain (the pain may be severe and present most of the time) Bowing of the legs and other visible deformities Enlarged head and skull deformities Fracture Headache Hearing [medlineplus.gov]

    In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. [ncbi.nlm.nih.gov]

    Bone pain at pagetic sites is an indication for treatment, as there is good evidence that this responds to bisphosphonate therapy. 3 In individual patients, it can be difficult to determine whether pain is arising from Paget’s disease or from coexisting [mja.com.au]

    Bone pain presents as constant, deep, and aching. [physio-pedia.com]

  • Asymptomatic

    "Sclerotic" lesions seen on radiographs were always asymptomatic. The involvement of ioints by Paget's disease was a major source of pain. [annals.org]

    Article Figures/Media Metrics Paget's disease of bone may present with bone pain but is often asymptomatic. [doi.org]

    A strong case can also be made for treating asymptomatic patients in whom the location of the disease puts them at risk of future complications. [mja.com.au]

    Asymptomatic patients also have no clinical signs of the disease. [symptoma.com]

  • Fatigue

    Case report: Sixty four years old woman, who addressed to our department in March 2011 for chronic left hip and low back pain, with insidious onset which has increased over time, fatigue, headaches attacks with occipital localization associated with dizziness [endocrine-abstracts.org]

    When Paget's disease is present in many bones the overactive osteoclasts have the ability to release enough calcium in the blood stream to cause hypercalcemia, which can cause symptoms such as fatigue, weakness, loss of appetite, abdominal pain, and constipation [physio-pedia.com]

    […] connected to the joint) bone fractures bone deformities (e.g., enlarged head, bowed legs, reduced height) pain or numbness (from pressure on nerves) headache hearing loss (when abnormally formed skull bones press on the nerve) warmth over an affected area fatigue [medbroadcast.com]

    This rare complication can lead to a number of symptoms, including: Fatigue Weakness Loss of appetite Abdominal pain Constipation Very rarely, Paget’s disease can progress to a type of bone cancer called Paget’s sarcoma. [orthoinfo.aaos.org]

    If symptoms occur, they develop insidiously, with pain, stiffness, fatigue, and bone deformity. Bone pain is aching, deep, and occasionally severe, sometimes worse at night. Pain also may arise from compression neuropathy or osteoarthritis. [msdmanuals.com]

  • Congestive Heart Failure

    Symptoms of congestive heart failure (as a large part of the body's blood may be diverted to the diseased bone). [musclesandjoints.com]

    A patient can rarely develop congestive heart failure because of the increased blood flow. Increased calcium levels from the bone remodeling process can cause kidney stones. [emedicinehealth.com]

    heart failure due to shunting of blood through warm skin (bone is hypervascular and hot) Leontiasis ossea : cranium too heavy to lift Platybasia : invagination of base of skull due to weak bone, compression of posterior fossa structures Associated neoplasms [pathologyoutlines.com]

    With very widespread Paget's disease, it is possible to develop congestive heart failure due to an increased workload on the heart. Sometimes the skin overlying the involved bone is warmer than usual. [medicinenet.com]

  • Limb Pain

    Paget's Disease affecting the spine may produce pain directly or as a result of nerve root irritation or compression. Pressure of the spinal cord is unusual. Limb pain may be due to the lesion itself or result from nerve root compression. [veterans.gc.ca]

    Continue discussing phantom limb pain with client. [slideplayer.com]

    […] than unaffected side)and thick (osteitis deformans) If generalised may ® headache, deafness (with impairment of hearing in 30 - 50% of cases), deformities, stiffness, limb pain and sometimes fracture and heart failure, occasionally pressure on the optic [flinders.edu.au]

Skin

  • Skin Disease

    A good diet and exercise might also help. nih: national institute of arthritis and musculoskeletal and skin diseases Codes M88 Osteitis deformans [Paget's disease of bone] M88.0 Osteitis deformans of skull M88.1 Osteitis deformans of vertebrae M88.8 Osteitis [icd10data.com]

    NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases ALP - blood test (Medical Encyclopedia) ALP isoenzyme test (Medical Encyclopedia) Paget disease of the bone (Medical Encyclopedia) [ Read More ] Paget disease of bone Paget disease [icdlist.com]

    NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases [medlineplus.gov]

    Stiffness Weakness Neurological Nerve compression conditions including cranial, spinal, and peripheral nerves Hearing loss Mental confusion due to deteriorated cognitive function Cardiovascular Heart failure Increased vascularity (causing increased skin [physio-pedia.com]

Ears

  • Tinnitus

    With skull implication, symptoms like headaches, hearing loss, vertigo, tinnitus, changes in vision and cranial nerve palsies occur. If the cranium descends onto the cervical spine, patients experience paresthesias and bowel or bladder incontinence. [symptoma.com]

    Changes in the skull may lead to inner ear damage, resulting in deafness, ringing in the ears (tinnitus), or impaired balance (vertigo). It may also result in headaches. [nmihi.com]

    Abstract A fifty-four year old woman with Paget's disease of the skull had progressive deafness and tinnitus for eight years prior to the diagnosis and operative removal of a large acoustic neurinoma. [amjmed.com]

    Enlarged bones in the head can put pressure on nerves leading to tinnitus (ringing or noises in the ear), dizziness, and headaches. Paget's disease usually progresses slowly. [medbroadcast.com]

  • Hearing Impairment

    If the skull is involved, there may be headaches and hearing impairment. Signs may include skull enlargement bitemporally and frontally (frontal bossing), dilated scalp veins, and nerve deafness in one or both ears. [msdmanuals.com]

    Six patients had audiometrically confirmed hearing impairment. Osteoporosis was present in five patients and dyslipidemia was noted in six patients. Six of our patients had hypertension. Serum ALP level at baseline was 1190.9 ± 666.1 IU/L. [ijem.in]

Eyes

  • Angioid Streaks of the Retina

    In addition to bowing of legs and cranial enlargement, signs can include a foreshortened spine and angioid streaks in the retina. [etsu.edu]

Musculoskeletal

  • Bone Pain

    Bisphosphonate therapy is primarily indicated for patients who have bone pain arising from increased metabolic activity in affected bones. [ncbi.nlm.nih.gov]

    They are thought to reduce bone turnover, improve bone pain, promote healing of osteolytic lesions and restore normal bone histology [ 1 ]. [patient.info]

    However, bone pain, bone enlargement, or bone deformity may occur. Bone pain may be deep, aching, and occasionally severe and may worsen at night. The enlarging bones may compress nerves, causing more pain. [merckmanuals.com]

  • Osteoporosis

    Osteoporosis is the result of bone loss, caused by a change in factors that regulate bone cell metabolism. The process of bone loss itself, resulting in osteoporosis, does not cause symptoms. [cambridge.org]

    A: Lateral radiograph of the skull shows the thickened skull and osteoporosis circumscripta of both lateral temporal bones (sho... FIG. 122.5. [5minuteconsult.com]

    Vulvar Paget's disease ulceration can occur in female reproductive organs.[9] Paget's disease is not associated with osteoporosis. Although Paget's disease and osteoporosis can occur in the same patient, they are different disorders. [en.wikipedia.org]

    CHMP concluded that the benefits of calcitonin for osteoporosis did not exceed the risks. The nasal spray's only indication is for osteoporosis, thus justifying the drug's removal from the market. [medscape.com]

    Osteoporosis screening: topic overview Health Link B.C. Osteoporosis Canada recommends everyone over age 65 have routine bone density tests. Start routine testing earlier if you are at increased risk for broken bones. [mcmasteroptimalaging.org]

  • Bone Disorder

    Osteitis deformans is a type of chronic bone disorder causing an increase in the breakdown and regrowth of bone tissue, typically resulting in enlarged or deformed bone formations. [yourlegalguide.com]

    Abstract Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. [ncbi.nlm.nih.gov]

    Paget's disease, also known as osteitis deformans, is a chronic bone disorder. It generally affects the growth of new bone in adults, and it leads to the formation of abnormally large, weak bones that break easily. [hss.edu]

    Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. [jhu.pure.elsevier.com]

    In Australia, it is the most common metabolic bone disorder after osteoporosis. Although its cause is unknown, people are more likely to develop Paget’s disease if someone else in their family has it. Paget’s disease is a bone disorder. [healthdirect.gov.au]

  • Back Pain

    In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. [ncbi.nlm.nih.gov]

    He had a history of low back pain and was noted to have an area of increasing numbness over the left buttock. A prominence of the left sacroiliac region was noticed and on rectal examination a bony hard mass was palpable posteriorly. [online.boneandjoint.org.uk]

    pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression.2 Paget's disease can reduce both function and mobility in the older people.3 In addition to newer tests for assessing the activity of Paget's disease, effective therapy [onlinelibrary.wiley.com]

    A 72-year-old male subject was evaluated in the Neurosurgery Outpatient division with a symptom of low back pain. Lumbar magnetic resonance imaging (MRI) detected spondylolisthesis and a lytic lesion in the L4 vertebral body. [go.gale.com]

  • Hip Pain

    (M2.OR.38) A 63-year-old male presents to his family physician with a chief complaint of right knee and hip pain as well as pain in his left upper arm. [step2.medbullets.com]

    Therefore, it is not unexpected that hip pain is one of the major presenting complaints. Analysis of the radiographs of 25 hips with one or more articular sufaces involved by Paget's disease demonstrated narrowing in 24. [ncbi.nlm.nih.gov]

    As axial bones are more frequently affected, patients usually describe lower back, cervical or hip pain. [symptoma.com]

Face, Head & Neck

  • Frontal Bossing

    The skull may enlarge, and the brow and forehead may look more prominent (called frontal bossing). A person may notice this enlargement when a larger hat is needed. [merckmanuals.com]

    Bone deformity (including sabre tibia (bowing of the tibia), kyphosis, frontal bossing of the skull, an enlarged maxilla, an increase in head size). Pathological fractures (may produce heavy bleeding from the very vascular bone). [patient.info]

    Skull involvement may produce enlargement of the head characterized by more evident frontal bossing and dilated superficial cranial muscles. If the facial bones are involved as well, a typical leonine appearance may be Noted. [veterans.gc.ca]

Neurologic

  • Headache

    First Aid for the Basic Sciences: Organ Systems by Tao Le Probably a slow paramyxovirus infection Mutation in RANK (Receptor Activator of Nuclear Factor k B) Symptoms 4) Rapid Review Pathology by Edward Goljan Bone pain (the most common complaint) Headaches [meddiction.com]

    With skull implication, symptoms like headaches, hearing loss, vertigo, tinnitus, changes in vision and cranial nerve palsies occur. If the cranium descends onto the cervical spine, patients experience paresthesias and bowel or bladder incontinence. [symptoma.com]

    If they do occur, symptoms may include: Bone pain, joint pain or stiffness, and neck pain (the pain may be severe and present most of the time) Bowing of the legs and other visible deformities Enlarged head and skull deformities Fracture Headache Hearing [medlineplus.gov]

    Clinical symptoms: headache, bowing and shortening of the legs, the arms appear relatively long, enlargement of the head (hat and dentures no longer fit), and in extreme cases a leontine facies develops (leontiasis ossea). [med-college.hu]

  • Vertigo

    Brain compression results in ataxia or dementia, while cranial nerve VII compression leads to deafness and vertigo. Patients may also present fractures as the first sign of disease. [symptoma.com]

    Changes in the skull may lead to inner ear damage, resulting in deafness, ringing in the ears (tinnitus), or impaired balance (vertigo). It may also result in headaches. [nmihi.com]

    May present with bone pain (constant, poorly localized pain that is present at rest), bone deformity, fracture, arthropathy, skin temperature changes, or neurologic complications (deafness, cranial nerve palsies, spinal cord compression, vertigo). [eorif.com]

    […] cartilage of affected joints, most commonly: spine cervical osteoarthritis thoracic osteoarthritis lumbar osteoarthritis ankle knee hip Headaches (from skull involvement) Conductive and/or sensorineural hearing loss (from temporal bone involvement) Vertigo [veterans.gc.ca]

  • Dizziness

    Case report: Sixty four years old woman, who addressed to our department in March 2011 for chronic left hip and low back pain, with insidious onset which has increased over time, fatigue, headaches attacks with occipital localization associated with dizziness [endocrine-abstracts.org]

    If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. [icdlist.com]

    The signs and symptoms displayed by Paget's Disease of the Bone could include: Bone pain Deformed bones, causing Bowed legs Enlarged skull Enlarged hips Curved backbone Easy fractures Headache, dizziness Vision and hearing defects Leg pain Numbness Weakness [dovemed.com]

    Enlarged bones in the head can put pressure on nerves leading to tinnitus (ringing or noises in the ear), dizziness, and headaches. Paget's disease usually progresses slowly. [medbroadcast.com]

    Enlarged skull bones may damage the inner ear (cochlea), which can cause hearing loss, and dizziness. The enlarged skull bones can compress nerves, which causes headaches. [merckmanuals.com]

  • Waddling Gait

    On clinical examination, patient was short stature, hunched back with a slow waddling gait. Patient had an enlarged cranium with broad, prominent forehead and severely protrusive, expanded maxilla, caused obliteration of nasolabial sulci. [amsjournal.com]

    gait) _Coxa_Valga Acetabular protrusion Osteoarthritis Fractures Bone enlargement Vertebral compression Muscular Myalgia Stiffness Weakness Neurological Nerve compression conditions including cranial, spinal, and peripheral nerves Hearing loss Mental [physio-pedia.com]

  • Abnormal Gait

    Orthotics help correct abnormal gait caused by bowed lower extremities. Some patients require orthopedic surgery (eg, hip or knee replacement, decompression of the spinal cord). Weight bearing should be encouraged, and bed rest should be avoided. [msdmanuals.com]

Workup

Asymptomatic patients also have no clinical signs of the disease. Physical examination may, however, reveal deformed or bowing bones, kyphosis (that may cause spinal cord compression and injury), warm teguments over the affected area, increased skull circumference, facial deformity or narrowing of the airways. Brain compression results in ataxia or dementia, while cranial nerve VII compression leads to deafness and vertigo. Patients may also present fractures as the first sign of disease.

Blood workup should include serum and bone-specific alkaline phosphatase, procollagen I N -terminal peptide and serum total acid phosphatase, all of which may be increased [5]. Even if serum alkaline phosphatase is normal, the disease cannot be excluded. Calcium and phosphate levels are usually normal in mobile patients but may be high if hyperparathyroidism coexists. Secondary hyperparathyroidism may appear due to increased calcium demand. Hyperuricemia has also been described [6].

Urine should be examined for specific markers like hydroxyproline, deoxypyridinoline, C-telopeptide (CTx) and N-telopeptide (NTx) [7]. Alpha-CTx/beta-CTx ratio is high in active disease patients and is a suitable marker to monitor therapy [8].

Plain radiographs are used both for disease and complication diagnose and monitoring, but the gold standard in documenting the extent of the pathological process is represented by Tc99m-MDP scintigraphy, despite the fact that this method is less specific than classical radiology. Computer tomography and magnetic resonance imaging are useful when trying to evaluate malignant transformation, nerve compression, and hydrocephalus.

Radiographs show osteolysis and aberrant bone formation, sclerotic areas, ankylosis, remineralization or heterogeneous ossification [9].

Bone biopsy reveals the typical mosaic pattern [10] that appears as a result of osteolysis, bone formation, and osteosclerosis. The architecture is disorganized and vascularization is abundant. In time, osteosclerosis becomes the most prominent feature.

X-Ray

  • Nephrolithiasis

    Nephrolithiasis and pyelonephritis with cortical and perinephric abscesses were also reported. [ncbi.nlm.nih.gov]

    […] syndrome Para or quadriplegia Cardiovascular Increased cardiac output All uncommon Congestive cardiac failure Aortic stenosis Endocardial calcification Atherosclerosis Metabolic Hypercalcaemia All are rare Hyperuricaemia Immobilization hypercalciuria Nephrolithiasis [doi.org]

  • Increased Bone Density

    bone density, increased microfractures, loss of distinction between cortex and medulla; may have sharp demarcation between normal and affected bone; may extend into soft tissue if florid disease Radiology images Contributed by Dr. [pathologyoutlines.com]

    […] is the gold standard and first treatment initiated to decrease osteoclastic activity, improve bone density, and increase the strength of the bone itself. [physio-pedia.com]

    […] parathyroidectomy experience increased bone density and repair of the skeleton within weeks. [en.wikipedia.org]

Serum

  • Alkaline Phosphatase Increased

    If alkaline phosphatase is not elevated or it is unclear whether the increased serum alkaline phosphatase is of bony origin (ie, if GGT is increased in proportion to alkaline phosphatase), a bone-specific fraction can be measured. [msdmanuals.com]

Treatment

Treatment Paget’s disease is treatable, but not all patients require treatment (see Box 4 ). [mja.com.au]

We suggest treatment with a bisphosphonate before surgery on pagetic bone. [ncbi.nlm.nih.gov]

Some start treatment if alkaline phosphatase levels are raised; others only start treatment if there are symptoms. Specific treatment is required for complications. Because of the risk of osteosarcoma, patients should be monitored indefinitely. [patient.info]

No cases were reported with zolidronic acid in the treatment of Paget's disease. [scielo.br]

Treatment The pharmacological treatment of PDB is targeted at reducing osteoclast function ( Table 2 ). Other treatment is aimed at relieving symptoms and complications of the illness. [academic.oup.com]

Prognosis

Prognosis of Paget’s Disease (osteitis deformans) With effective treatment prognosis is good and long term remissions can be achieved. [healthengine.com.au]

The prognosis for people with Paget disease is most often very good. However, the few people who develop bone cancer have a poor prognosis. [merckmanuals.com]

The serum phosphatase is a most useful prognostic guide in a disease with a generally poor prognosis. Magnesium metabolism in relation to bone sarcoma requires further study. [online.boneandjoint.org.uk]

The former affects elderly patients, and has a poor prognosis and response to treatment1. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma. [path.upmc.edu]

Etiology

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Here, we review the epidemiology, etiology, pathology, macrostructure, histology, and quantitative histomorphometry findings of PDB. [ncbi.nlm.nih.gov]

Your browser doesn't support javascript. mh:"Osteitis Deformans/etiology" (213) 1. [pesquisa.bvsalud.org]

The etiology of Paget’s disease of bone remains unknown, but evidence supports both genetic and viral etiologies. [accessmedicine.mhmedical.com]

Abstract Although abundant evidence of concomitant cardiovascular disease is scattered throughout the literature on osteitis deformans, appreciation of the etiologic relationship between the two diseases has been lacking. [ahajournals.org]

Epidemiology

Imbalance between osteoclasts and osteoblasts Paget's Disease of Bone Epidemiology: What population does this affect? Arises in late adulthood (over 50) Paget's Disease of Bone Epidemiology: This arises in late adulthood (over 50). [quizlet.com]

Here, we review the epidemiology, etiology, pathology, macrostructure, histology, and quantitative histomorphometry findings of PDB. [ncbi.nlm.nih.gov]

Epidemiology Second most prevalent skeletal disease after osteoporosis Sex: ♂ > ♀ (1.2:1) Age of onset: > 55 years References:[1][2][3] Epidemiological data refers to the US, unless otherwise specified. Pathophysiology PDB is an idiopathic disease. [amboss.com]

Genetic Predisposition to Disease/epidemiology, Osteitis Deformans/epidemiology, Osteitis Deformans/etiology, Surveys and Questionnaires, Adult, Age Distribution, Aged, Canada/epidemiology, Cross-Sectional Studies, DNA Mutational Analysis, Environment [pesquisa.bvsalud.org]

Pathophysiology

*This picture above helps us in understanding the pathophysiology behind PAGET'S disease : *PATHOPHYSIOLOGY OF PAGET'S DISEASE: - The principal abnormality in Paget disease is the increased number and activity of osteoclasts. - Pagetic osteoclasts are [ourorthopaedics.blogspot.com]

Pathophysiology PDB is an idiopathic disease. PDB is associated with a high rate of bone remodeling. [amboss.com]

Pathophysiology and treatment of Paget's disease of bone, 2nd edn. London: Martin Dunitz, 1998. Rheumatology Vol. 44 No. 2 © British Society for Rheumatology 2005; all rights reserved [doi.org]

Although our understanding of the pathophysiology of PDB has advanced tremendously over the past 10 years, many questions remain unanswered, such as the mechanisms responsible for the focal nature of the disease and the recent changes in prevalence and [ncbi.nlm.nih.gov]

Pathophysiology 2) Wikipedia – Paget’s Disease Bone affected by Paget’s Disease Initially, there is a marked increase in the rate of bone resorption in localized areas, caused by large and numerous osteoclasts. [meddiction.com]

Prevention

Utilize isometric exercises to prevent muscle atrophy & to strengthen the muscle. Isometrics prevent joint from being immobilized. Position client with pillows to prevent strain on unaffected areas. Turn every 2 hours to prevent complications. [slideplayer.com]

Medical and surgical treatment is discussed with the recommendation that surgery is kept to a minimum and covered by prophylactic antibiotics to prevent osteomyelitis. Sudden enlargement of the involved bones should raise the suspicion of malignancy. [ncbi.nlm.nih.gov]

(This is to prevent hearing loss.) The calcium levels are elevated and causing symptoms. Drug therapy helps prevent further bone breakdown and formation. Currently, there are several classes of drugs used to treat Paget disease. [medlineplus.gov]

Paget’s Disease of the Bone cannot be prevented. [dovemed.com]

References

  1. Gordon G. Metabolic bone disease in practice. Am Pract Dig Treat. 1951;2:113.
  2. Clegg J. Paget's disease. Lancet. 1937;2:128.
  3. Ashworth C. Atherosclerotic valvular disease of the heart. Arch Path. 1946;42:285.
  4. Sutton D. Mitral stenosis. M Clin North Am. 1944;28: 47.
  5. Alvarez L, Guañabens N, Peris P, et al. Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. J Bone Miner Res. 1995;10(3):458-65.
  6. Lluberas-Acosta G, Hansell JR, Schumacher HR Jr. Paget's disease of bone in patients with gout. Arch Intern Med. 1986;146(12):2389-92.
  7. Alexandersen P, Peris P, Guañabens N, et al. Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone. J Bone Miner Res. 2005;20(4):588-95.
  8. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008;83(9):1032-45.
  9. Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics. 2002;22(5):1191-216.
  10. Seitz S, Priemel M, Zustin J, et al. Paget's disease of bone: histologic analysis of 754 patients. J Bone Miner Res. 2009;24(1):62-9.
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