Paget's bone disease is placed among the metabolic osteopathies because it is characterized by a conspicuous alteration of the bone remodeling. As discussed below, its etiopathogenesis is not however fully clarified. Paget's bone disease occurs at an advanced age. It is a very common condition after osteoporosis. It has a long course and generally has a phase of acute, or florid phase, which can be followed by a phase of attenuation that can pass into a further florid phase. It can be localized to a single skeletal segment (monostotic forms) or to several segments (polyostotic forms), as well as starting in one segment, attenuating it and presenting itself in a florid form in another skeleton district.
Paget, spongy bone, alteration of the bone trabeculae |
Microscopically, the most striking finding during the florid phase is
represented by the notable increase in bone remodeling, which however is
extremely disordered. It is initially supported by a large increase in
osteoclasts, which present an excessive number of nuclei, some of which can be
pycnotic and coarctated. The equilibrium that normally exists between
osteoclasts and osteoblasts is generally maintained, so that a high number of
osteoblasts and an active osteogenesis with the production of a matrix of the
interwoven fibers type are also observed.
This is reflected in a conspicuous increase in serum alkaline phosphatase which,
together with the increased urinary finding of hydroxyproline and other collagen
catabolites, which are indices of increased bone resorption, has an important
diagnostic significance. However, the osteogenesis process is not spatially
related to reabsorption, but occurs chaotically without any correlation with
Howship loopholes. Such a disorderly process of reabsorption and repair is
responsible on the one hand for a "porosity" of the bone due to the numerous
unprotected osteoclastic gaps; on the other hand it determines the formation of
coarse and irregular trabeculae, without connection or irregularly
connected. These findings were in the past included under the names of "hypertrophied
atrophy" or "porotic hyperostosis", which still retain a descriptive meaning.
Variable degrees of fibrosis and a large number of ectatic blood vessels can be
observed in the medullary spaces of the spongy bone. In the compact bone of the
long bones, conspicuous subperiosteal ossification occurs on the tensioned
cortical slopes, which is the main cause of the increased bone volume and which
can cause roughness and irregularity of the surface, up to the production of
osteophytes.
At the level of the rachis it is possible to have a narrowing of
the medullary canal. The neo-deposit matrix is generally regularly calcified.
From what has been said it is clear that, apart from the conspicuous disorder
that characterizes remodeling, the bone alteration is similar to that found in
severe hyperparathyroidism: a notable increase in osteoclasts and bone
resorption, a more or less corresponding increase in osteogenetic activity and
of osteoblasts, production of intertwined fibrous bone, fibrosis of the
medullary spaces in which highly ectatic blood vessels run. The electron
microscopic examination of the pagetic bone in the florid phase has allowed,
however, to find some characteristic alterations. They were indeed
observed in the included nuclear and cytoplasmic osteoclasts consisting of
elongated, filamentous-tubular structures, with a thickness of about 15 nm and
an internal diameter of about 5-7 nm, which often arrange themselves to form
paracrystalline structures.
Paget, TRAP staining, active osteoclasts in red |
They are mostly contained in the picnotic and coarctated nuclei found on histological examination, considered by some to be apoptosis. Both for their ultrastructure and for their immunohistochemical reactions, the nuclear included were considered as aggregates of paramyxovirus capsids and it was considered that Paget's bone disease could be supported by attenuated virus infection. This hypothesis appears in agreement with the fact that the bone Paget has other characteristics typical of such diseases, such as the long course, the prolonged period of clinical latency, the presence of giant polynuclear cells (osteoclasts) containing viral included, the possible familiarity of the affirmation . It has also been suggested that the viruses in question may be those of measles.
However, no definitive conclusion has been reached, either because
nucleocapsids of other viruses (respiratory syncytial, murine and canine
distemper) have been identified by three nucleocapsids of the measles virus, and
because the same type of nucleocapsids has been found in relevant osteoclasts.
to non-pagetic osteopathies, including some of genetic origin. It is possible
that there is some predisposition to contract the disease, as seems to indicate
the occurrence of several cases in the same family nucleus. It is interesting,
but for now without explanation, the fact that the frequency of Paget's bone
disease is much greater in some areas of the world (France and England in Europe,
Australia and New Zealand) than in others (China, India, Malaysia) . In the
United States, the disease is more common in European whites. If the florid
phase of Paget's bone disease is followed by remission, there is a gradual
attenuation of the degree of bone remodeling: the osteoclasts decrease in number,
the depletion-absorption holes become less frequent and are repaired by the
formation of new bone, the number of osteoblasts gradually normalizes. The
previous florid phase, however, remains documented by the presence of numerous
cementing lines, which indicate the limit at which the phase of reabsorption of
the numerous and disorderly BMUs had stopped and the reversal phase had
intervened and, subsequently, of repair. The result is a characteristic aspect,
called "mosaic", because the numerous residual cementing lines of the disordered
resorption and reconstruction activity delimit bone-like zones arranged in such
a way as to remember the tesserae of a mosaic.
A fearful complication of Paget's bone disease is the appearance of an
osteosarcoma, a likely consequence of the increased cell turnover. Furthermore,
the development of so-called "osteoclastomas", ie benign tumors, is susceptible
to recurrence, histologically constituted by numerous giant multinuclear cells
which, to be positive for the TRAP reaction, belong to the osteoclastic line.
They may have a variable number of coarct and pseudo nuclei, which contain the
included already described in the osteoblasts.