Pagets disease of bone

Stages of Pagets disease of bone

Osteolytic stage

Mixed osteoclastic-osteoblastic stage (ends with predominance of osteoblastic activity)

Osteosclerotic stage (burnt-out, quiescent stage)

Histologic findings in Chronic Pagets Disease

Histologic hallmark is mosaic pattern of lamellar bone.  Likened to jigsaw puzzle pieces, this pattern is produced by prominent cement lines that anneal haphazardly oriented pieces of lamellar bone.  At end-stage, bone is larger than normal, composed of coarsely thickened trabeculae, and soft, porous cortices that lack structural stability.

Clinical symptoms

Pathological fractures (“chalk-stick fractures”)

Enlarged skull (“changing hat size”, leontitis ossea)

Localized pain secondary to microfractures and bone growth causing compression of nerves

Secondary osteoarthritis

High output heart failure

Pathogenesis of Paget’s Disease of the Bone

Slow virus infection (paramyxovirus) causing IL-6, M-CSF release from infected cells, which act to recruit osteoclasts and stimulate resorptive activity

Suggestion that osteoclasts are abnormal and hyperreactive to activating agents such as vitamin D and RANKL.

Genetic predisposition with potential linkage to a locus on chromosome 18q