Paget Disease of Bone

Overview
  • Paget Disease of the bone, also known as Osteitis Deformans, is a disorder caused by osteoclast hyperactivity, yielding focal areas of excessive bone remodeling that over time heal in a haphazard, structurally weak arrangement prone to deformation and fracture. Onset is almost always in the elderly with a slight predilection for men.
Etiology and Pathogenesis
  • The etiology of Paget Disease is unknown and both genetic and environmental factors are suspected. Several lines of evidence have pointed to the possibility that an as yet unidentified paramyxovirus similar to measles virus may be the initial trigger for the diseae. Whatever the case, the underlying derangement of Paget Disease appears to be that of the osteoclast, resulting in hyperactive osteoclast activation and consequent excessive bone remodeling.
Morphology
  • Overview
    • The morphology of Paget Disease evolves through three phases beginning with the "Osteolytic Phase" which is followed by a "Mixed Phase" characterized by both bone resorption and formation and ending with a "Sclerotic Phase". A minority of patients display only a single lesion whereas most harbor multiple simultaneous foci of involvement that can display in different phases of the disease.
  • Osteolytic Phase
    • The initial osteolytic phase of Paget Disease is typified by the prominent vascularization as well as the presence of numerous multi-nucleated osteoclasts surrounding involved bone with accompanying evidence of bone resorption.
  • Mixed Phase
    • During the mixed phase, osteoclast-mediated bone resorption continues but is now accompanied by evidence of new bone formation. Vascularization of affected bone begins to decline as the lesion evolves into its sclerotic phase.
  • Sclerotic Phase
    • The final Sclerotic Phase sees a gradual end to osteoclast activity but is typified by progressive formation of haphazardly arranged bone in a characteristic "woven" architecture. The mosaic pattern of the newly formed bone deposition stands in contrast to the normal lamellar architecture and is structurally weaker, yielding a propensity for fracture or deformation.
Clinical Consequences
  • Presentation
    • Paget Disease is asymptomatic in most patients and comes to light only due to an unexpectedly elevated alkaline phosphatase level, an unspecific marker of osteoclast activity. Occasionally radiography for a different indication may reveal characteristic lytic lesions.
    • When clinical consequences do arise they typically center around bone pain. Patients may also present with the structural sequelae of the disease that include gradual deformity or bony overgrowths. The disease typically affects the skull, vertebrae, pelvis, and long bones of the lower extremities. Deformation and over-growth of these bones can impinge on nearby nerves, commonly affecting the cranial nerves and leading to palsies, that may manifest as hearing loss or deafness.
  • Complications
    • The most common complication of Paget Disease is pathologic fractures. In rare cases the hyper-vascularity seen in the osteolytic phase of the disease may be so prominent that patients are pushed into high-output heart failure. In some patients, affected bone will develop bone tumors, most commonly osteosarcoma.