Pathology

Any bone may be affected, and in the worst cases, several will be involved. Alternating phases of rapid bone resorption and formation account for the pathology seen.

• Paget’s disease affects the osteoclasts primarily, these are increased in both number and size and results in excessive bone resorption
• in response, bone formation is also markedly increased. This rapid deposit of new bone by the osteoblasts results in formation of bone which is poor in quality and the collagen fibers assume a haphazard irregular mosaic pattern (woven bone) rather than lamellar bone (1,2)
• this process begins as a wedge of destructive osteoclasts at one end of a bone and will ultimately ends up disrupting the entire structure (3)

Macroscopically, the long bones may have thickened shafts and deformities. Cysts and stress fractures may be seen in both vertebrae and long bones. In the skull, the calvarium may be thickened. There may be areas of localised softening, known as osteoporosis circumscripta.

Pagetic bone is generally thickened, irregular and brittle.

Microscopically, three phases are defined:

• an initial osteolytic phase - osteoclasts produce large excavations which are filled with vascular fibrous tissue
• a mixed lytic and sclerotic phase - osteoblasts lay down woven bone which is subsequently resorbed by osteoclasts
• a burnt out quiescent osteosclerotic stage - osteoclasts are less active and the eroded areas are filled with brittle, woven bone.

A tile-like mosaic of osteoid cement lines demarcate the old resorption cavities. This pattern is pathognomonic of Paget's disease of bone.

Reference:

• (1) Roodman GD, Windle JJ. Paget disease of bone. J Clin Invest. 2005;115(2):200-8.
• (2) Michou L, Brown JP. Emerging strategies and therapies for treatment of Paget's disease of bone. Drug Des Devel Ther. 2011;5:225-39.
• (3) Whyte MP. Clinical practice. Paget's disease of bone. N Engl J Med.2006;355(6):593-600.