Part of “CHAPTER 65 – PAGET DISEASE OF BONE“

The initial abnormality in Paget disease is a marked increase in the rate of bone resorption at localized sites, mediated by large and numerous pagetic osteoclasts. In response to the increased bone resorption, large numbers of osteoblasts are recruited to these sites and promote a compensatory increase in new bone formation. The osteoblasts probably are inherently normal, although a possible pathologic role for these cells in the initiation of the pagetic process has not been completely excluded.

The earliest phase of Paget disease is represented radiographically by an advancing lytic wedge or “blade of grass” lesion in a long bone, or by osteoporosis circumscripta, as seen in the skull. The next phase is a mixture of the initial abnormality, increased bone resorption, and a compensatory increase of new bone formation. Both osteoclasts and osteoblasts are found at active sites in this stage. Presumably because of the rapidity of the process, newly deposited collagen fibers are laid down in a haphazard, rather than a linear, fashion, creating a mosaic pattern in bone—a more primitive woven bone—instead of the normal lamellar pattern. The bone marrow becomes infiltrated by an excess of fibrous connective tissue, and a marked increase in blood vessels is seen, which causes the bone to become hyper-vascular. Usually, the bone matrix is normally mineralized, although areas of reduced mineralization (widened osteoid seams) can be found in isolated areas of some bone biopsy specimens.5 Eventually, the hypercellularity at a given locus may decrease, leaving only the sclerotic mosaic bone (“burned out” disease) without evidence of active bone turnover. Usually, all different phases are seen concomitantly in different areas of pagetic involvement in a given patient. Figure 65-3 compares the appearance of normal and pagetic bone by scanning electron
microscopy, and Figure 65-4A shows the pattern of woven bone in Paget disease.