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Paget Disease, Emergency Medicine

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Paget Disease, Emergency Medicine

Basics

Description

Treatment indicated in patients with symptomatic disease or asymptomatic disease located in areas where complications can occur

731.0 Osteitis deformans without mention of bone tumor

  • Paget disease involves resorption of normal bone and its replacement with fibrous and sclerotic tissue
  • Also known as osteitis deformans
  • Usually focal, bones most frequently involved include:Pelvis (70%)Femur (55%)Skull (42%)Tibia (32%)Spine (53%, lumbar spine)Flat bones
  • Usually found incidentally and generally asymptomatic
  • Occurs in ’ ˆ Ό1 " “2% of patients >55 yr old
  • Incidence increases with age
  • Starts with resorptive or osteolytic phase, during which osteoclasts remove healthy bone
  • Hypervascularity begins in resorptive phase:Predisposes to hematoma and fracture
  • Resorbed bone is eventually replaced by irregular, dense, disorganized trabecular bone in sclerotic or osteoplastic phase forming "mosaic pattern " 
  • Malignant transformation is rare:Osteosarcoma is malignancy of concernUsually malignant transformation occurs in 1%
  • More common in men
  • More common in European descent
  • Less common in Asian or Scandinavian descent
  • Typically involves 1 bone (monostotic)
  • May involve a few bones (polyostotic)
  • Pelvis (70%)
  • Femur (55%)
  • Skull (42%)
  • Tibia (32%)
  • Spine (53%, lumbar spine)
  • Flat bones
  • Predisposes to hematoma and fracture
  • Osteosarcoma is malignancy of concern
  • Usually malignant transformation occurs in 1%

Etiology

  • Unknown
  • Genetic component:SQSTM1 mutation seen in many but not all cases
  • Environmental influences may also play a rolePresence of nucleocapsids from measles, canine distemper, paramyxovirus, or respiratory syncytial virus may implicate viral causePossible association with rural life and close contact with farm animals
  • May represent vascular hyperplasia with subsequent inflammation
  • Increased nucleoli and intranuclear inclusion bodies seen in osteoclasts on microscopy
  • SQSTM1 mutation seen in many but not all cases
  • Presence of nucleocapsids from measles, canine distemper, paramyxovirus, or respiratory syncytial virus may implicate viral cause
  • Possible association with rural life and close contact with farm animals

Diagnosis

Signs and Symptoms

  • Many patients are asymptomatic, with disease discovered by incidental radiographs or elevated alkaline phosphatase levels
  • Deep, aching bone pain occurs late in the clinical course
  • Pain with weight bearing if femur or tibia involvement
  • Pain worse with rest in nonweight-bearing bones
  • Acute (resorptive/osteolytic) phase:Pathologic fracturesPain from acute lysis, fracture, or resultant arthritisHypercalcemia or renal stonesHypervascularity may result in significant bleeding if affected bone is fracturedWidespread disease:Increased vascularity and blood flow may result in high-output cardiac failure
  • Secondary (sclerotic/osteoplastic) phase:Long-bone involvement may present with swelling or deformity and gait abnormalitySkull involvement may cause headaches or abnormal skull shape (change in hat size)Severe skull or spine involvement may result in CNS compressionHearing loss may result from nerve compression or ossicle involvement
  • Pathologic fractures
  • Pain from acute lysis, fracture, or resultant arthritis
  • Hypercalcemia or renal stones
  • Hypervascularity may result in significant bleeding if affected bone is fractured
  • Widespread disease:Increased vascularity and blood flow may result in high-output cardiac failure
  • Increased vascularity and blood flow may result in high-output cardiac failure
  • Long-bone involvement may present with swelling or deformity and gait abnormality
  • Skull involvement may cause headaches or abnormal skull shape (change in hat size)
  • Severe skull or spine involvement may result in CNS compression
  • Hearing loss may result from nerve compression or ossicle involvement

Essential Workup

  • Diagnosis usually suggested by radiographs
  • Thorough neurologic exam must be documented, especially with vertebral or pelvis involvement

Diagnosis Tests & Interpretation

  • Alkaline phosphatase is the most dramatic marker of disease activity
  • Calcium and phosphate levels should be checked as well, but are usually normal
  • Hypercalcemia seen in immobilization or presence of a fracture, but if elevated in an ambulatory patient, suspect hyperparathyroidism
  • EKG if suspect hypercalcemia and CXR with evidence of high-output cardiac failure
  • Increased bone formation may lead to elevations in urine hydroxyproline or serum osteocalcin or procollagen fragments
  • Alterations in parathyroid hormone (PTH) levels occur as secondary changes during resorptive/osteolytic phase (low PTH) and sclerotic/osteoplastic phase (high PTH)
  • Plain x-rays:During resorptive phase, lytic lesions are often not seen, except in skull, where lesions are well demarcated (osteoporosis circumscripta)Bowing of long bones may occur with resorption and strength lossNew bone initially appears irregular and spotty, and later becomes homogeneous and dense ( "ivory pattern " )Excess bone may be deposited along stress lines, leading to cortical irregularities and thickening
  • CT or MRI defines margins and helps evaluate for neoplasm or hematoma:Spiral CT to detect renal calculi
  • Radionuclide bone scans useful to evaluate extent and activity of disease
  • Plain films are usually all that is needed in acute setting to identify/manage fractures
  • During resorptive phase, lytic lesions are often not seen, except in skull, where lesions are well demarcated (osteoporosis circumscripta)
  • Bowing of long bones may occur with resorption and strength loss
  • New bone initially appears irregular and spotty, and later becomes homogeneous and dense ( "ivory pattern " )
  • Excess bone may be deposited along stress lines, leading to cortical irregularities and thickening
  • Spiral CT to detect renal calculi

Differential Diagnosis

  • Primary hyperparathyroidism
  • Multiple myeloma
  • Hodgkin variants
  • Acromegaly
  • Osteosarcoma

Treatment

Pre-Hospital

  • Pre-hospital personnel should obtain information about mechanism of injury or social factors that suggest pathologic fracture
  • Adequate immobilization can limit excessive bleeding around fracture site

Initial Stabilization/Therapy

  • Airway management and resuscitation, as indicated
  • High-output cardiac failure should be treated as outlined in CHF chapter
  • Prompt immobilization of fractures will limit excessive bleeding around fracture site

Ed Treatment/Procedures

  • Analgesia for pain of lytic lesions, fractures, or arthritis includes acetaminophen and narcotics
  • Fracture treatment is often more conservative, owing to difficulties with bleeding during operative repair
  • Orthopedic consultation for severe arthritis and definitive fracture management
  • Hypercalcemia may be treated with IV fluids, calcitonin, and/or bisphosphonates
  • CNS compression requires emergent neurosurgical consultation and possible decompression

Medication

  • Nitrogen-containing bisphosphonates:Pamidronate: 30 mg IV daily ƒ — 3 consecutive days; infuse over 4 hrAlendronate: 40 mg PO daily for 6 moRisedronate: 30 mg PO daily for 2 moZoledronic acid: 5 mg IV ƒ — 1; infuse over at least 15 min
  • Pamidronate: 30 mg IV daily ƒ — 3 consecutive days; infuse over 4 hr
  • Alendronate: 40 mg PO daily for 6 mo
  • Risedronate: 30 mg PO daily for 2 mo
  • Zoledronic acid: 5 mg IV ƒ — 1; infuse over at least 15 min
  • Simple bisphosphonates and calcitonin:Etidronate: 5 mg/kg PO daily for 6 moTiludronate: 400 mg PO daily for 3 moCalcitonin: 50 " “100 U SC as tolerated; not for >6 mo
  • Chemotherapy and simple bisphosphonates no longer recommended
  • Use of calcitonin and simple bisphosphonates are limited to patients who cannot tolerate or who are allergic to the nitrogen-containing bisphosphonates
  • Side effects of bisphosphonates include influenza like syndrome and jaw osteonecrosis
  • Often need supplemental vitamin D and Ca to maintain normal Ca levels during treatment
  • Etidronate: 5 mg/kg PO daily for 6 mo
  • Tiludronate: 400 mg PO daily for 3 mo
  • Calcitonin: 50 " “100 U SC as tolerated; not for >6 mo

Follow-Up

Disposition

  • Admission as indicated for major trauma or injury, or excessive bleeding
  • Orthopedic procedures
  • Hypercalcemia
  • CNS compressive symptoms, nerve entrapment requiring surgery
  • No evidence of significant bleeding, neurologic compromise, or hypercalcemia, and adequate pain control
  • Appropriate fracture immobilization and orthopedic follow-up
  • Referral is based upon any acute injuries
  • May also consider referral to endocrinologist within 1 " “2 wk of discharge

Follow-Up Recommendations

  • Follow-up is generally driven by the acute injury that led to the radiographs on which the diagnosis of Paget disease was made
  • Response to pharmacologic treatment aimed at correction of serum alkaline phosphatase levels
  • Consider repeat pharmacologic treatment if rise in serum alkaline phosphatase, return of symptoms, or disease progression seen radiographically

Pearls and Pitfalls

  • The diagnosis of Paget disease is usually made as an incidental finding on radiographic imaging
  • Prompt immobilization of fractures will limit excessive bleeding around fracture site
  • Consider Paget disease if elevation of alkaline phosphatase is present without any other explanation

Additional Reading

  • Cundy ‚ T, Reid ‚ IR. Pagets disease of bone. Clin Biochem. 2012;45:43 " “48.
  • Lojo Olivieria ‚ L, Torrijos Eslava ‚ A. Treatment of Paget's disease of bone. Reumatol Clin. 2012;8:220 " “224.
  • Ralston ‚ SH, Langston ‚ AL, Reid ‚ IR. Pathogenesis and management of Paget's disease of bone. Lancet. 2008;372:155 " “163.
  • Whyte ‚ MP. Clinical practice. Paget's disease of bone. N Engl J Med. 2006;355:593 " “600.

See Also (Topic, Algorithm, Electronic Media Element)

Codes

ICD9

ICD10

  • M88.9 Osteitis deformans of unspecified bone
  • M88.88 Osteitis deformans of other bones
  • M88.859 Osteitis deformans of unspecified thigh
  • M88.0 Osteitis deformans of skull
  • M88.1 Osteitis deformans of vertebrae
  • M88.869 Osteitis deformans of unspecified lower leg

SNOMED

  • 2089002 osteitis deformans (disorder)
  • 203340003 Pagets disease of pelvis (disorder)
  • 203342006 Paget's disease-femur (disorder)
  • 203351003 Paget's disease of skull (disorder)
  • 203329006 Paget's disease-lumbar spine (disorder)
  • 203344007 Paget's disease-tibia