Paget's Disease

Source:  Paget's Disease    Tag:  lytic phase


An autosomal dominant condition of abnormal bone remodeling where original osseous tissue is reconstucted through active interplay between excessive bone resorption and abnormal new bone formation 
  • may be monostotic or polystotic
  • increased osteoclastic bone resorption is the primary cellular abnormality 
  • cause is thought to be a virus (intra-nucleur nucleocapsid-like structure)
  • Peak incidence in the 5th decade of life.
    • common in europeans
  • Phases
    • lytic phase: intense osteoclastic resorption
    • mixed phase: resorption and compensatory bone formation
    • scelotic phase: bone formation predominates
  • Malignancy
    • less than 1% will develop malignant Paget's sarcoma (secondary sarcoma) 
      • osteosarcoma is the most common, followed by fibrosarcoma and chondrosarcoma
    • Paget's sarcoma has a poor prognosis with long term survival of < 20%
Symptoms
  • frequently asymptomatic and found incidentally
  • pain may be the presenting symptom
  • be suspicious for Paget's secondary sarcoma in a patient with a known history of Pagets who complains of new onset intense pain.

Laboratory findings 
  • elevated alkaline phosphatase
  • elevated hydroxyproline (collagen breakdown marker)
  • increased urinary N-telopeptide and alpha-C-telopeptide 

  • Radiographs
  • show remodeled cortices and coarsened trabeculae which give the bone a blastic appearance
    • Paget's secondary sarcoma
      • shows cortical bone destruction
      • soft tissue mass
  • Bone scan
    • intensely hot in lytic and mixed phase
    • less hot in sclerotic phase
  • Characteristic histology
  • irregular broad trabeculae with disorganized cement lines 
    • numerous large osteoclastics with multiple nuclei per cell 
    • fibrous vascular tissue interspersed between trabeculae
Treatment
  • Nonoperative
    • goal of treatment is to inhibit osteoclastic activity
    • pharmocologic treatment includes
      • bisphophonates
        • Didronel is an older generation medication that inhibited osteoclasts and osteoblasts, and therefore could not be used for more that 6 months at a time
        • Pamidronate is a newer generation medication that only inhibits osteoclasts. The disadvantage is that it comes in IV form only
      • calcitonin
      • methotrexate
  • Operative
    • hip and knee arthroplasty
      • often indicated due to joint involvement
      • treat paget's with pharmocologic agents prior to arthroplasty to reduce excessive bleeding
    • Metaphyseal osteotomy and plate fixation 
      • Fractures through pathologic bowing of long bones
      • Impending pathologic fracture of long bone with bowing deformity