Rheumatology Book

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Paget's Disease of Bone

Aka: Paget's Disease of Bone, Paget's Disease, Paget Disease of Bone, Paget Disease, Osteitis Deformans, Pagetic Lesion
  1. Definitions
    1. Paget Disease of Bone
      1. Benign skeletal condition of increased focal bone resorption and disordered bone formation
    2. Pagetic Lesion
      1. Focal region of bone resorption and disordered bone formation
  2. Epidemiology
    1. Prevalence (United States)
      1. Overall: 1-2%
      2. Age over 80 years: 10%
    2. Onset over age 50 years
      1. Incidence doubles every decade over age 50 years old
      2. Rare under age 40 years old
    3. Gender
      1. Males are slightly more likely than women to be affected (RR 1.5)
    4. Ethnicity and Regions
      1. Uncommon in Asia and Scandanavia
      2. Common in United States, Europe, Australia, and New Zealand
  3. Pathophysiology
    1. Focal bone resorption and disordered bone formation
      1. Phase 1: Intense Osteoclastic activity
        1. Bone resorption predominates
        2. Bone turnover is 20 times normal rate
      2. Phase 2: Osteolytic-Osteoblastic activity
        1. Osteoclastic activity stimulates reflexive Osteoblastic activity
        2. Results in poorly organized, woven bone formation
        3. Ineffective mineralization
      3. Phase 3: Dense bone deposition
        1. Resulting bone is disorganized, deformed and sclerotic with increased vascularity
        2. Resulting bone is more fragile, weaker than normal bone
        3. Involved Bone Marrow is also fibrotic
    2. Pagetic Lesions (focal areas of bone abnormalities)
      1. Monostotic Pagetic Lesions
        1. Single site focus of bone abnormality
      2. Polyostotic Pagetic Lesions
        1. Multiple focal sites of bone abnormality
    3. Distribution
      1. Pelvis (72%)
      2. Spine
        1. Lumbar (58%)
        2. Thoracic (45%)
        3. Cervical (14%)
      3. Skull (42%)
      4. Long bones
        1. Femur (55%)
        2. Tibia (35%)
        3. Humerus (31%)
    4. Associated factors (etiology unknown)
      1. Viral antigen association (especially paramyxoviruses including Measles)
      2. Diet and toxin exposure may also play a role
      3. Family History
        1. Autosomal Dominant (with incomplete penetrance)
        2. Positive Family History present in 10-20% of cases
        3. Family History may confer up to a 10 fold increased risk
        4. Sequestrome-1 or SQSTM1 (on Chromosome 5) encodes ubiquitin-binding p62 protein
          1. SQSTM1 Mutations are responsible for 50% of familial and 30% of sporadic cases
  4. Symptoms
    1. Asymptomatic in 70% of cases
      1. Most cases are found incidentally (elevated Alkaline Phosphatase, xray abnormalities)
    2. Pain (74%)
      1. Most common presenting symptom (but typically occurs later in course)
      2. Mild to moderate constant pain (severe sharp pain may suggest pathologic Fracture)
      3. Results from osteolytic activity, bone deformities or adjacent Osteoarthritis
      4. Pain provocative factors
        1. Rest or night pain
        2. Weight bearing
        3. Warming
      5. Pain palliative measures
        1. Activity
    3. Bone deformity (18%)
    4. Hearing Loss (8%)
    5. Pathologic Fractures (6%)
    6. Headaches
    7. Radiculopathy
    8. References
      1. Tan (2014) Calcif Tissue Int 95(5): 385-92 [PubMed]
  5. Signs
    1. Kyphosis
    2. Limb shortening or bowing
      1. Tibia anterior bowing
      2. Femur anterolateral bowing
    3. Frontal forehead bossing
    4. Skull enlargement
    5. Loose teeth
    6. Limp
  6. Labs: Diagnosis
    1. Liver Function Tests with Alkaline Phosphatase
      1. Total serum Alkaline Phosphatase
      2. Bone specific Alkaline Phosphatase
    2. Other markers
      1. Procollagen Type 1 N-Terminal Proptide
      2. Urinary cross-linked N-terminal telopeptide of type 1 collagen
      3. Urinary hydroxyproline is no longer used as marker
  7. Labs: Monitoring
    1. Screening if first degree relative has Paget's Disease
      1. Alkaline Phosphatase every 3 years (over age 50)
    2. Monitoring of diagnosed Paget's Disease
      1. Alkaline Phosphatase every 3 to 12 months
  8. Imaging: XRay
    1. Indications
      1. Focal pain or deformity
      2. Alkaline Phosphatase with unexplained elevation but no focal pain or deformity to guide imaging
        1. Skull XRay
        2. Facial Bone XRay
        3. Abdominal XRay
        4. Tibia-Fibula XRay
    2. General changes
      1. Combined focal osteolytic lesions with nearby osteosclerosis
      2. Bone deformity or enlargement
      3. Cortical thickening
      4. Loss of corticomedullary distinction
      5. Pronounced bone trabeculae
    3. Skull changes
      1. Osteoporosis circumscripta cranii
    4. Long bone changes
      1. Flame-shaped changes
      2. Limb bowing
      3. Fractures (banana-shaped transverse Fractures)
  9. Imaging: Bone Scan (Technetium-99m)
    1. Focal areas of intense and homogenous radiotracer uptake
    2. Appearance of Mouse-face on Vertebrae
  10. Complications
    1. Pathologic Fractures
      1. Long Bone Fractures
      2. Vertebral Compression Fractures
    2. Neurologic (esp. Nerve Compression Syndromes from direct pressure)
      1. Hearing Loss (Cochlear involvement)
      2. Vertigo
      3. Cranial Nerve palsy
      4. Spinal stenosis or radiculopathy resulting in weakness, numbness or Paresthesias
      5. Hydrocephalus
      6. Headache
    3. Hypercalciuria and Hypercalcemia (uncommon)
      1. Associated with polyostotic disease (multiple focal Pagetic Lesions) AND immobilization or Fracture
      2. Ureterolithiasis risk
      3. Significant Hypercalcemia is rare
    4. High Output Cardiac Failure (rare)
      1. Associated with severe polyostotic disease (multiple focal Pagetic Lesions) with marked increased vascularity
    5. Malignant degeneration (1% of Paget's Disease)
      1. Osteosarcoma (most common of malignant complications)
      2. Chondrosarcoma
      3. Giant Cell tumors
      4. Fibrosarcoma
      5. Spindle cell Sarcoma
    6. Other complications
      1. Pseudomalignancy (Pseudosarcoma or pseudo giant cell)
      2. Osteoarthritis (Paget's Disease involving joint)
  11. Management: General Measures
    1. Adequate pain control
    2. Low impact Exercise
    3. Avoid straining affected bone
    4. Calcium Supplementation 1000 mg orally daily
    5. Vitamin D 400 IU per day
  12. Management: Suppress bone resorption (Osteoclasts)
    1. Indications
      1. Symptomatic patients
        1. Bone pain
        2. Hearing Loss
        3. Nerve Compression Syndromes
        4. XRay identified osteolytic lesions
      2. Active Paget's Disease (or complication risk of untreated Paget's Disease)
      3. Alkaline Phosphatase >125 to 150% of normal
    2. First line agents: Bisphosphonates
      1. Avoid in advanced Chronic Kidney Disease, Hypocalcemia, pregnancy
      2. Zoledronic acid (Reclast) 5 mg IV once (preferred)
        1. Re-evaluate with total serum Alkaline Phosphatase at 1-2 years
        2. Retreatment may be needed after 5 years from prior dose
      3. Alternative Bisphosphonate protocols
        1. Risedronate (Actonel) 30 mg daily for 2 months
        2. Alendronate (Fosamax) 40 mg daily for 6 months
    3. Alternatives (not as potent as Bisphosphonates)
      1. Calcitonin 100 U SC or IM daily for 6 to 18 months
      2. Avoid Teriparatide (Forteo) due to increased risk of Osteosarcoma
    4. Monitoring
      1. Total serum Alkaline Phosphatase
        1. Baseline
        2. Month 3-6 after treatment
          1. Consider retreatment if no response to therapy (esp. when not using Zoledronic Acid)
        3. Every 6-12 months (every 1-2 years if Zoledronic acid used)
      2. XRay
        1. Repeat XRay at one year after treatment if osteolytic lesions were present before treatment
  13. References
    1. Simon in Klippel (1997) Primer Rheumatic, p. 382-4
    2. Schneider (2002) Am Fam Physician 65(10):2069-72 [PubMed]
    3. Rianon (2020) Am Fam Physician 102(4): 224-8 [PubMed]

Osteitis Deformans (C0029401)

Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (CHV) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass.
Definition (MEDLINEPLUS)

Paget's disease of bone causes your bones to grow too large and weak. They also might break easily. The disease can lead to other health problems, too, such as arthritis and hearing loss. You can have Paget's disease in any bone, but it is most common in the spine, pelvis, skull, and legs. The disease might affect one or several bones, but not your entire skeleton. More men than women have the disease. It is most common in older people.

No one knows what causes Paget's disease. In some cases, a virus might be responsible. It tends to run in families. Many people do not know they have Paget's disease because their symptoms are mild. For others, symptoms can include

  • Pain
  • Enlarged bones
  • Broken bones
  • Damaged cartilage in joints

Doctors use blood tests and imaging tests to diagnose Paget's disease. Early diagnosis and treatment can prevent some symptoms from getting worse. Treatments include medicines and sometimes surgery. A good diet and exercise might also help.

NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Definition (MSHCZE) Pagetova nemoc – kostní onemocnění neznámé příčiny, projevující se zduřením a přestavbou některých kostí. Často jsou postiženy kosti lebky vč. maxilly. Dochází k deformitám kostních alveolů, tvrdého patra apod. Onemocnění může být provázeno silnými bolestmi, poruchami hlavových nervů, poruchami sluchu, sklonem k spontánním frakturám atd. V důsledku zvýšené vaskularizace v metabolicky vysoce aktivních kostech může dojít k zvýšení srdečního výdeje (hyperkinetická cirkulace). Diagnosticky je charakteristický rtg nález, nápadné je zvýšení kostního izoenzymu alkalické fosfatázy. Léčebně se podávají bisfosfonáty, kalcitonin; další léčba je symptomatická (analgetika, chirurgický zákrok). (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI_NCI-GLOSS) A chronic condition in which both the breakdown and regrowth of bone are increased. Paget disease of bone occurs most frequently in the pelvic and leg bones, skull, and lower spine. It is most common in older individuals, and may lead to bone pain, deformities, and fractures.
Definition (NCI) A disease of bone that initially results in the excessive resorption of bone (by osteoclasts) followed by the replacement of normal bone marrow with vascular and fibrous tissue.(On-line Medical Dictionary)
Definition (MSH) A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.
Definition (CSP) disease marked by repeated episodes of increased bone resorption followed by excessive repair, resulting in weakened, deformed bones of increased mass.
Concepts Disease or Syndrome (T047)
MSH D010001
ICD10 M88, M88.9
SnomedCT 2089002, 203354006, 156812003, 156811005, 203353000
English PAGET'S BONE DISEASE, Osteitis Deformans, Paget Disease of Bone, Paget's Disease of Bone, Pagets Disease, Bone, Paget's disease, OSTEITIS DEFORMANS, Paget's disease NOS, Paget's disease OS, Paget's disease of bone [osteitis deformans], Paget's disease of bone, unspecified, PDB, PAGET DISEASE OF BONE, PAGET DIS OF BONE, PAGETS DIS OF BONE, Bone Paget's Disease, Bone Paget Disease, Paget's disease (diagnosis), Osteitis deformans [Paget's disease of bone], Osteitis Deformans [Disease/Finding], Unspecified Paget's disease of bone, Disease;Pagets (bone), paget's disease, paget's disease of the bone, paget's bone disease, paget's disease of bone, paget bone disease, Pagets disease of bone, Paget Disease, Bone, Osseous Paget's Disease, Paget's disease NOS (disorder), Paget's disease of bone (disorder), Paget's disease OS (disorder), Paget disease of bone, osteitis deformans, Osteitis deformans, Paget's disease of bone, Osteitis deformans (disorder), bone; Paget, Paget; bone, Paget; osteitis deformans, deformans; osteitis, osteitis deformans; Paget, osteitis; deformans, Paget's Disease of the Bone, Paget's Disease, Pagets Disease (Bone), Pagets (bone) disease
Dutch ziekte van Paget van bot, ziekte van Paget, Paget; bot, Paget; osteitis deformans, bot; Paget, deformans; osteïtis, osteitis deformans; Paget, osteïtis; deformans, Ziekte van Paget van bot, niet gespecificeerd, osteitis deformans, Ziekte van Paget van bot [osteitis deformans], Osteitis deformans, Paget, ziekte van, Ziekte van Paget
French Maladie de Paget osseuse, Maladie de Paget, Maladie osseuse de Paget, Maladie de Paget des os, Ostéite déformante hypertrophique, Ostéite déformante hypertrophiante
German Paget-Krankheit der Knochen, Paget-Krankheit, Osteodystrophia deformans [Paget-Krankheit], Osteodystrophia deformans, nicht naeher bezeichnet, Ostitis defromans, Osteodystrophia deformans, Ostitis deformans, Morbus Paget (Knochen), Paget-Krankheit (Knochen)
Italian Malattia ossea di Paget, Malattia di Paget, Morbo di Paget, Osteite deformante
Portuguese Doença de Paget do osso, Doença de Paget, Doença de Paget do Osso, Doença de Paget Óssea, Doença Óssea de Paget, Osteíte deformante, Osteíte Deformante
Spanish Enfermedad ósea de Paget, Enfermedad de Paget, Enfermedad de Paget de los Huesos, Osteítis Deformante, enfermedad de Paget, SAI (trastorno), enfermedad de Paget, SAI, enfermedad de Paget ósea (trastorno), Enfermedad de Paget Ósea, Enfermedad Ósea de Paget, enfermedad de Paget ósea, osteítis deformante (trastorno), osteítis deformante, Osteitis deformante
Swedish Osteitis deformans
Japanese ヘンケイセイコツエン, コツパジェットビョウ, Paget骨病, 骨炎-変形性, パジェット骨病, ページェット骨病, 変形性骨炎, 奇形性骨炎, 骨Paget病, Paget病-骨, ページェット病-骨, 骨パジェット病, 骨ページェット病
Finnish Pagetin luutauti
Russian OSTIT DEFORMIRUIUSHCHII, OSTEODISTROFIIA DEFORMIRUIUSHCHAIA, OSTEIT DEFORMIRUIUSHCHII, PEDZHETA BOLEZN', OSTOZ DEFORMIRUIUSHCHII, ОСТЕИТ ДЕФОРМИРУЮЩИЙ, ОСТЕОДИСТРОФИЯ ДЕФОРМИРУЮЩАЯ, ОСТИТ ДЕФОРМИРУЮЩИЙ, ОСТОЗ ДЕФОРМИРУЮЩИЙ, ПЕДЖЕТА БОЛЕЗНЬ
Czech Deformující osteitida, Pagetova nemoc, osteodystrophia deformans, Pagetova kostní nemoc, osteitis deformans
Korean 뼈의 파젯병[변형성 골염], 상세불명의 뼈의 파젯병
Croatian OSTEITIS DEFORMANS
Polish Choroba Pageta kości
Hungarian Paget-kór, Osteitis deformans, Csont Paget-kórja
Norwegian Osteitis deformans, Pagets beinsykdom, Pagets bensykdom
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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