Paget Disease, Emergency Medicine

Basics

Description

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 ’ 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 concern
- Usually 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)

Etiology

Unknown
Genetic component:
- SQSTM1 mutation seen in many but not all cases
Environmental influences may also play a role
- 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
May represent vascular hyperplasia with subsequent inflammation
Increased nucleoli and intranuclear inclusion bodies seen in osteoclasts on microscopy

Generally not seen in children

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 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
Secondary (sclerotic/osteoplastic) phase:
- 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

Lab

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)

Imaging

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 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
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

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

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

Nitrogen-containing bisphosphonates:
- Pamidronate: 30 mg IV daily 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 1; infuse over at least 15 min

Second Line

Simple bisphosphonates and calcitonin:
- 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
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

Follow-Up

Disposition

Admission Criteria

Admission as indicated for major trauma or injury, or excessive bleeding
Orthopedic procedures
Hypercalcemia
CNS compressive symptoms, nerve entrapment requiring surgery

Discharge Criteria

No evidence of significant bleeding, neurologic compromise, or hypercalcemia, and adequate pain control
Appropriate fracture immobilization and orthopedic follow-up

Issues for Referral

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.

Codes

ICD9

731.0 Osteitis deformans without mention of bone tumor

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

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